Study To Evaluate The Efficacy And Safety Of Oral PF-06651600 And PF-06700841 In Subjects With Moderate To Severe Crohn's Disease

A PHASE 2A, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ORAL PF-06651600 AND PF-06700841 AS INDUCTION AND OPEN LABEL EXTENSION TREATMENT IN SUBJECTS WITH MODERATE TO SEVERE CROHN'S DISEASE

The objectives of this study are to evaluate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06651600 (200 mg for 8 weeks followed by 50 mg for 4 weeks) dosed once daily and PF-06700841 (60 mg for 12 weeks) dosed once daily during an induction period of 12 weeks, followed by an open label extension period at doses of 50 mg and 30 mg of PF 06651600 and PF 06700841, respectively, for 52 weeks.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: Placebo PF-06700841; Drug: PF-06700841; Drug: PF-06651600 Placebo; Drug: PF-06651600

• Study Type: Interventional
• Enrollment (Actual): 244
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Mater Misericordiae Ltd
  • Victoria
    • Ballarat, Victoria, Australia, 3350
      • Ballarat Base Hospital
  • Western Australia
    • Subiaco, Western Australia, Australia, 6008
      • Saint John of God Health Care Inc.
• Austria
  • Wien, Austria, 1090
    • AKH Wien Universitaetsklinik fuer Innere Medizin III
• Belgium
  • Jette, Belgium, 1090
    • University Hospital Brussels
  • Leuven, Belgium, 3000
    • University Hospitals Leuven
  • Liége, Belgium, 4000
    • CHC MontLegia
• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina, 78000
    • Javna zdravstvena ustanova Univerzitetski klinicki centar Republike Srpske,
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Winnipeg Regional Health Authority - Health Sciences Centre, Winnipeg
• Croatia
  • Split, Croatia, 21000
    • Klinicki Bolnicki centar Split, Zavod za gastroenterologiju
  • Zagreb, Croatia, 10000
    • Klinicka bolnica Dubrava Zagreb
  • Zagreb, Croatia, 10000
    • Klinicki bolnicki centar Zagreb, Zavod za gastroenterologiju i hepatologiju
• Czechia
  • Horovice, Czechia, 268 31
    • Nemocnice Horovice, a.s.
  • Hradec Kralove, Czechia, 500 12
    • Hepato-Gastroenterologie HK s.r.o.
  • Hradec Kralove, Czechia, 500 12
    • Medialpharma s.r.o.
  • Olomouc, Czechia, 77900
    • MUDr. Gregar s.r.o.
  • Strakonice, Czechia, 386 29
    • Nemocnice Strakonice, a.s.
  • Strakonice, Czechia, 386 01
    • Nemocnice Strakonice, a.s., Interni oddeleni
• Georgia
  • Tbilisi, Georgia, 0159
    • Institute of Clinical Cardiology, Ltd.
  • Tbilisi, Georgia, 0112
    • LTD "Acad. F. Todua Medical Center - LTD Research Institute of Clinical Medicine"
  • Tbilisi, Georgia, 0141
    • The First University Clinic of TSMU
• Germany
  • Berlin, Germany, 10318
    • Paian MED Research GmbH
  • Berlin, Germany, 14163
    • Krankenhaus Waldfriede e.V.,
  • Kiel, Germany, 24105
    • Universitaetsklinikum Schleswig-Holstein
• Hungary
  • Bekescsaba, Hungary, 5600
    • Bekes Megyei Kozponti Korhaz, Rethy Pal Tagkorhaz
  • Budapest, Hungary, 1125
    • Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak
  • Budapest, Hungary, 1088
    • Semmelweis Egyetem, II. Belgyogyaszati Klinika
  • Szekszard, Hungary, 7100
    • Clinfan Szolgaltato Kft.
• Italy
  • Messina, Italy, 98125
    • A.O.U. Policlinico G. Martino
  • Padova, Italy, 35128
    • Azienda Ospedaliera di Padova
  • Roma, Italy, 00128
    • Policlinico Universitario Campus Bio-Medico
  • BS
    • Brescia, BS, Italy, 25123
      • A.O.Spedali Civili
  • Bari
    • Castellana Grotte, Bari, Italy, 70013
      • Irccs Saverio de Bellis
  • CZ
    • Catanzaro, CZ, Italy, 88100
      • Univ. "Magna Graecia" di Catanzaro
  • MB
    • Monza, MB, Italy, 20090
      • ASST Monza
  • Milan
    • Rozzano, Milan, Italy, 20089
      • Istituto Clinico Humanitas IRCCS - Sez. Autonoma di Malattie, Infiammatorie Croniche Intestinali
• Korea, Republic of
  • Seoul, Korea, Republic of, 02447
    • Kyung Hee University Hospital
  • Seoul, Korea, Republic of, 03181
    • Kangbuk Samsung Hospital
  • Korea
    • Daegu, Korea, Korea, Republic of, 41944
      • Kyungpook National University Hospital
• Lebanon
  • Achrafieh, Lebanon
    • Saint George Hospital University Medical Center
  • Beirut, Lebanon
    • American University of Beirut Medical Center
  • El Chouf, Lebanon
    • Ain Wazein Medical Village
  • Saida, Lebanon
    • Hammoud Hospital University Medical Center
• Poland
  • Katowice, Poland, 40-659
    • Niepubliczny Zaklad Opieki Zdrowotnej ALL-MEDICUS
  • Kielce, Poland, 25-355
    • ETG Kielce
  • Knurow, Poland, 44-190
    • Indywidualna Specjalistyczna Praktyka Lekarska Maciej Zymla
  • Knurow, Poland, 44-190
    • Szpital w Knurowie Sp. z o.o.
  • Koscian, Poland, 64-000
    • Samodzielny Publiczny Zespół Opieki Zdrowotnej, Pracownia Endoskopii
  • Lodz, Poland, 90-349
    • Osrodek Badan Klinicznych Appletreeclinics
  • Lodz, Poland, 90-302
    • Centrum Medyczne Szpital Swietej Rodziny Sp z o.o.
  • Lodz, Poland, 90-302
    • Pracownia Endoskopii Centrum Medyczne Szpital Swietej Rodziny Sp z o.o.
  • Lodz, Poland, 92-551
    • SALVE
  • Lublin, Poland, 20-582
    • GASTROMED Sp. z o.o.
  • Piotrkow Trybunalski, Poland, 97-300
    • IRMED
  • Piotrkow Tryunalski, Poland, 91-300
    • Samodzielny Szpital Wojewodzki im. M. Kopernika w Piotrkowie Trybunalskim
  • Poznan, Poland, 61-113
    • Ai Centrum Medyczne Sp. Z O.O. Sp.K.
  • Poznan, Poland, 61-441
    • Gabinety Lekarskie Rivermed
  • Poznan, Poland, 60-848
    • PRZYCHODNIA SPECJALISTYCZNA MEDIC-R Clinical Research Center Spolka z ograniczona odpowiedzialnoscia
  • Poznan, Poland, 61-315
    • AM-MEDIC SP. z o.o.
  • Poznan, Poland, 61-731
    • PRZYCHODNIA SPECJALISTYCZNA MEDIC-R Clinical Research Center Spolka z ograniczona odpowiedzialnoscia
  • Pulawy, Poland, 24-100
    • KO-MED Centra Kliniczne
  • Pulawy, Poland, 24-110
    • Zaklad Opieki Zdrowotnej Medical Sp. z o.o., (endoscopy)
  • Sopot, Poland, 81-756
    • ENDOSKOPIA Sp. z o. o.
  • Sroda Wielkopolska, Poland, 63-000
    • Szpital Sredzki Serca Jezusowego sp. z o.o.
  • Staszow, Poland, 28-200
    • Nowe Zdrowie-CK, Kiełtucki i Wspólnicy Sp.j.
  • Szczecin, Poland, 71-434
    • Twoja Przychodnia Szczecinskie Centrum Medyczne
  • Szczecin, Poland, 71-685
    • SONOMED
  • Warszawa, Poland, 00-728
    • WIP Warsaw IBD Point Profesor Kierkus
  • Warszawa, Poland, 00-635
    • Centrum Zdrowia MDM
  • Warszawa, Poland, 02-653
    • Endoterapia PFG Sp. z o.o.
  • Wloclawek, Poland, 87-800
    • Centrum Diagnostyczno-Lecznicze Barska Sp. z o. o.
  • Wroclaw, Poland, 50-088
    • FutureMeds
  • Wroclaw, Poland, 53-114
    • LexMedica
  • Wroclaw, Poland, 50-449
    • Melita Medical Sp. z o.o.
  • Wroclaw, Poland, 50-555
    • Centrum Gastrologiczno Hepatologiczne
  • Wroclaw, Poland, 54-130
    • Golden Care
  • Dolnoslaskie
    • Strzegom, Dolnoslaskie, Poland, 58-150
      • STRZEGOMSKIE CENTRUM MEDYCZNO-DIAGNOSTYCZNE Sp. z o.o.
  • Other
    • Swidnica, Other, Poland, 58-100
      • DC-MED Sp. z o.o. Sp.k.
  • Silesia
    • Tychy, Silesia, Poland, 43-100
      • H-T. Centrum Medyczne-Endoterapia
• Russian Federation
  • Izhevsk, Russian Federation, 426061
    • LLC "Alliance Biomedical-Ural Group"
  • Moscow, Russian Federation, 105554
    • Llc "Olla-Med"
  • Moscow, Russian Federation, 119435
    • Sechenov University on the base of Institute of Translational Medicine and Biotechnology
  • Novosibirsk, Russian Federation, 630005
    • Limited Liability Company "Medical Center SibNovoMed"
  • Novosibirsk, Russian Federation, 630007
    • Novosibirskiy Gastrocenter
  • Omsk, Russian Federation, 644050
    • Clinic at FSBEI HE "Omsk State Medical University" MoH RF
  • Pyatigorsk, Russian Federation, 357500
    • LLC "New Clinic"
  • Saint Petersburg, Russian Federation, 196143
    • LLC "Research Center Eco-Safety"
  • Saint-Petersburg, Russian Federation, 194354
    • Limited Liability Company "Medical Center "Reavita Med SPb" (OOO "MC "RM SPb")
  • Saint-Petersburg, Russian Federation, 195220
    • Limited Liability Company "RIAT"
  • Saint-Petersburg, Russian Federation, 197343
    • Limited Liability Company "RIAT SPb"
  • Samara, Russian Federation, 443093
    • Limited Liability Company Medical Company "Hepatolog"
  • Samara, Russian Federation, 443011
    • Private Institution Educational Organization of Higher Education
  • Samara, Russian Federation, 443029
    • Non-state Healthcare Institution 'Railway Clinical Hospital at Samara Station of Open Joint Stock
  • St. Petersburg, Russian Federation, 197706
    • Saint-Petersburg State Budgetary Healthcare Institution "City Clinical Hospital of the Righteous
  • Stavropol, Russian Federation, 355017
    • State Budgetary Healthcare Institution of the Stavropol Region
  • Saint-petersburg
    • Pushkin, Saint-petersburg, Russian Federation, 196603
      • Private medical institution "Euromedservice"
  • Sestroretsk
    • Saint-Petersburg, Sestroretsk, Russian Federation, 197706
      • SPb SBIH "City Hospital #40 of the Kurortnyi region"
  • Stavropol Region
    • Pyatigorsk, Stavropol Region, Russian Federation, 357502
      • Polyclinic Ultrasound 4D LLC
  • Udmurt Republic
    • Izhevsk, Udmurt Republic, Russian Federation, 426061
      • LLC "Alliance Biomedical-Ural Group"
• Saudi Arabia
  • Riyadh, Saudi Arabia, 11426
    • King Abdulaziz Medical City
  • Riyadh, Saudi Arabia, 11472
    • King Khalid University Hospital
• Serbia
  • Beograd, Serbia, 11040
    • KBC "Dr Dragisa Misovic-Dedinje"
  • Beograd
    • Zemun, Beograd, Serbia, 11080
      • Klinicko Bolnicki Centar "Bezanijska Kosa"
  • Srbija
    • Kragujevac, Srbija, Serbia, 34000
      • Klinički centar Kragujevac
    • Subotica, Srbija, Serbia, 24000
      • Opsta bolnica Subotica
    • Zrenjanin, Srbija, Serbia, 23000
      • Opsta Bolnica "Djordje Joanovic", Odeljenje Interno, Odsek Gastroenterologija
• Slovakia
  • Banska Bystrica, Slovakia, 975 17
    • Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica
  • Vranov nad Toplou, Slovakia, 093 01
    • ENDOMED, s.r.o.
• South Africa
  • Gauteng
    • Parktown, Gauteng, South Africa, 2193
      • Wits Clinical Research Trial Site
  • Western CAPE
    • Claremont, Western CAPE, South Africa, 7708
      • Dr Wright Private Practice
• Spain
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marqués de Valdecilla
  • Madrid
    • Alcorcon, Madrid, Spain, 28922
      • Hospital Universitario Fundacion Alcorcon
• Switzerland
  • Zürich, Switzerland, CH-8091
    • UniversitätsSpital Zürich
• Tunisia
  • Tunis, Tunisia, 1007
    • La Rabta Hospital
  • Tunis, Tunisia, 1008
    • Habib Thameur Hospital
• Turkey
  • Ankara, Turkey, 06230
    • Hacettepe Üniversitesi Tip Fakültesi
  • Kocaeli, Turkey, 41380
    • Kocaeli Universitesi Tip Fakultesi
  • Mersin, Turkey, 33110
    • Mersin Universitesi Tip Fakultesi Hastanesi
  • Mersin, Turkey, 33110
    • Mersin Universitesi Tip Fakultesi Hastanesi, Ic Hastaliklari
  • Zonguldak, Turkey, 67600
    • Bulent Ecevit Universitesi Tip Fakultesi
• Ukraine
  • Chernivtsi, Ukraine, 58001
    • Regional Municipal Non-profit Enterprise "Chernivtsi Regional Clinical Hospital", Surgery Department
  • Kharkiv, Ukraine, 61037
    • Municipal Healthcare Institution Kharkiv City Clinical Hospital #2 n.a. prof. O.O. Shalimov
  • Kyiv, Ukraine, 01023
    • Medical Centre Medical Clinic Blagomed LLC
  • Kyiv, Ukraine, 04078
    • Municipal Non-profit enterprise of Kyiv Regional Council "Kyiv regional hospital"
  • Kyiv, Ukraine, 04107
    • Municipal non-profit enterprise of Kyiv regional council "Kyiv regional clinical hospital"
  • Kyiv, Ukraine, 02091
    • Medical Center "OK Clinic+" of International Institute of Clinical Trials
  • Kyiv, Ukraine, 03680
    • Medical Center "Universal clinic Oberig" of "Kapital" LLC, Gastro center
  • Lviv, Ukraine, 79007
    • Lviv clinical hospital on Railway Transport of Health Care Center branch of PJSC Ukrainian Railway
  • Vinnytsia, Ukraine, 21000
    • Vinnytsia City Clinical Hospital No.1
  • Vinnytsia, Ukraine, 21001
    • Private Small-Scale Enterprise Medical Center "Pulse"
  • Vinnytsia, Ukraine, 21005
    • Vinnytsia Regional Clinical Hospital for War Veterans
  • Vinnytsia, Ukraine, 21018
    • Vinnytsia Regional Clinical Hospital n.a. M.I.Pyrohov
  • Zaporizhzhia, Ukraine, 69076
    • Medical Center "DIACENTER"LLC
• United Arab Emirates
  • Dubai, United Arab Emirates, PO BOX 505240
    • Emirates Specialty Hospital
• United States
  • Alabama
    • Dothan, Alabama, United States, 36301
      • Dothan Surgery Center
    • Dothan, Alabama, United States, 36305
      • Gut P.C., dba Digestive Health Specialists of the Southeast
  • California
    • Beverly Hills, California, United States, 90210
      • Brighton Surgical Center
    • Los Angeles, California, United States, 90036
      • Entertainment Medical Group
    • Los Angeles, California, United States, 90067
      • Gastrointestinal Biosciences Clinical Trials, LLC
    • Redwood City, California, United States, 94063
      • Stanford Medicine Outpatient Center - Digestive Health Center
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Peak Gastroenterology Associates
    • Colorado Springs, Colorado, United States, 80903
      • Front Range Endoscopy Center
  • Florida
    • Clearwater, Florida, United States, 33756
      • Gastro Florida
    • Clearwater, Florida, United States, 33756
      • West Coast Endoscopy Center
    • Clearwater, Florida, United States, 33762
      • Gastro Florida
    • Clearwater, Florida, United States, 33756-3839
      • Gastro Florida
    • Jacksonville, Florida, United States, 32207
      • UF Health Jacksonville - Gastroenterology Emerson
    • Orlando, Florida, United States, 32819
      • HMD Research LLC
    • Orlando, Florida, United States, 32811
      • Millenia Surgery Center
  • Idaho
    • Boise, Idaho, United States, 83706
      • Treasure Valley Medical Research
  • Kansas
    • Shawnee Mission, Kansas, United States, 66217
      • WestGlen Gastrointestinal Consultants, P.A.
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • MGG Group Co., Inc., Chevy Chase Clinical Research
    • Chevy Chase, Maryland, United States, 20815
      • Chevy Chase Endoscopy Center
    • Rockville, Maryland, United States, 20850
      • Capitol Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02115
      • Mass Eye and Ear, Longwood
    • Chestnut Hill, Massachusetts, United States, 02467
      • Brigham and Women's Hospital
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Clinical Research Institute of Michigan, LLC
    • Macomb, Michigan, United States, 48044
      • Eastside Endoscopy Center
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
    • New York, New York, United States, 10021
      • Weill Cornell Medical College - New York Presbyterian Hospital
    • New York, New York, United States, 10065
      • Weill Cornell Medical College - New York Presbyterian Hospital
    • New York, New York, United States, 10065
      • New York Presbyterian Hospital - Weill Cornell Medical College (Colonoscopy)
    • New York, New York, United States, 10065
      • New York Presbyterian Hospital - Weill Cornell Medical College Investigational Pharmacy
    • New York, New York, United States, 10065
      • Weill Cornell Medical College - New York Presbyterian Hospital (Endoscopy Suite)
    • North Massapequa, New York, United States, 11758-1853
      • DiGiovanna Institute for Medical Education And Research
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
    • Chapel Hill, North Carolina, United States, 27514
      • UNC Hospitals
    • Chapel Hill, North Carolina, United States, 27517
      • UNC Hospitals Endoscopy Center at Meadowmont
    • Hillsborough, North Carolina, United States, 27278
      • UNC GI Procedures Hillsborough
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem, LLC
    • Winston-Salem, North Carolina, United States, 27103
      • Gastroenterology Associates of the Piedmont, PA
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group
    • Kingsport, Tennessee, United States, 37660
      • Holston Valley Surgery Center
    • Nashville, Tennessee, United States, 37204
      • Vanderbilt GI Endoscopy Lab at One Hundred Oaks
    • Nashville, Tennessee, United States, 37212-1375
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37204
      • Vanderbilt Inflammatory Bowel Disease Clinic
    • Nashville, Tennessee, United States, 37212-1610
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37232-5543
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Inflammatory Bowel Disease Clinic
  • Texas
    • Bellaire, Texas, United States, 77401
      • First Street Hospital
    • Bellaire, Texas, United States, 77401
      • First Street Surgical Center
    • Houston, Texas, United States, 77004
      • Hermann Drive Surgical Hospital
    • Houston, Texas, United States, 77047
      • Pearland Surgery Center
    • Southlake, Texas, United States, 76092
      • GI Alliance
    • Southlake, Texas, United States, 76092
      • Lonestar Endoscopy, LLP
    • Southlake, Texas, United States, 76092
      • Texas Digestive Disease Consultants (Administrative, Regulatory)
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Gastroenterology Associates of Northern Virginia
    • Fairfax, Virginia, United States, 22031
      • Verity Research, Inc.
    • Fairfax, Virginia, United States, 22031
      • Gastroenterology Associates of Northern VA
    • Lynchburg, Virginia, United States, 24502
      • Blue Ridge Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male and/or female subjects 18 years to 75 years of age
2. Documented diagnosis of ileal, ileocolonic, or colonic CD with a minimum disease duration of 3 months, as determined by endoscopic and histopathology assessment.
3. Endoscopic confirmation of active disease with total SES CD total score of at least 7. For isolated ileal disease, SES CD total score should be at least 4.
4. An average daily liquid/soft stool frequency (SF) greater than or equal to 2.5 or daily abdominal pain (AP) greater than or equal to 2.0.

5. Must have inadequate response to, loss of response to, or intolerance to at least one conventional therapy for CD:

   •Steroids; Immunosuppressants (azathioprine [AZA], 6 MP, or methotrexate [MTX]); Anti TNF inhibitors (infliximab, adalimumab,certolizumab); Anti integrin inhibitors (eg, vedolizumab); Anti IL 12/23 inhibitor (ustekinumab).

6. Subjects currently receiving the following treatment for CD are eligible providing they have been on stable doses as described below:

   • Oral corticosteroids (prednisone or equivalent up to 25 mg/day; budesonide up to 9 mg/day). Stable dose for at least 2 weeks prior to baseline. If oral corticosteroids have been recently discontinued, they must have been stopped at least 2 weeks prior to baseline. Decreases in steroid use due to AEs are allowed.
   • Oral 5 ASA or sulfasalazine are allowed providing that the dose is stable for at least 4 weeks prior to baseline.
   • Crohn's disease related antibiotics are allowed providing that the dose is stable for at least 4 weeks prior to baseline. If antibiotics are stopped prior to baseline, they must be discontinued at least 4 days prior to baseline.

Exclusion Criteria:

1. Diagnosis of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, diverticular disease, ulcerative colitis (UC), or clinical findings suggestive of UC.
2. Presence of active (draining) fistulae or intra abdominal or perineal abscesses.
3. Strictures with obstructive symptoms.
4. Short bowel syndrome.
5. History of bowel perforation requiring surgical intervention within the past 12 months.
6. Previous bowel surgery resulting in an existing stoma. Subjects who have a j pouch are excluded, as a j pouch can result in a stoma.
7. History of bowel surgery within 6 months prior to baseline.
8. Subjects displaying clinical signs of fulminant colitis or toxic megacolon.
9. Subjects with primary sclerosing cholangitis.
10. Subjects with evidence of colonic adenomas, dysplasia or neoplasia.
11. Abnormal findings on the chest x ray film such as presence of tuberculosis (TB), general infections, heart failure, or malignancy.
12. Any history of either untreated or inadequately treated latent or active TB infection, current treatment for active or latent TB infection or evidence of currently active TB by chest x ray, residing with or frequent close contact with individual(s) with active TB.

13. Subjects receiving the following therapies within the time period described below or expected to receive any of these therapies during the study period:

    1. >9 mg/day of oral budesonide or >25 mg/day of prednisone or equivalent oral systemic corticosteroid dose within 2 weeks prior to baseline.
    2. IV, IM (parenteral), or topical (rectal) treatment of 5 ASA or corticosteroid enemas/suppositories within 2 weeks prior to baseline.
    3. Azathioprine, 6 mercaptopurine, or methotrexate within 2 weeks prior to baseline.

    4. Anti TNF inhibitors (or biosimilars thereof) as described below:

       • Infliximab within 8 weeks prior to baseline;
       • Adalimumab within 8 weeks prior to baseline;
       • Certolizumab within 8 weeks prior to baseline;
    5. Anti integrin inhibitors (eg, vedolizumab) within 8 weeks prior to baseline.
    6. Ustekinumab within 8 weeks prior to baseline.
    7. Interferon therapy within 8 weeks prior to baseline.
    8. Subjects with prior treatment with lymphocyte depleting agents/therapies within 1 year prior to baseline (eg, CamPath[alemtuzumab], alkylating agents [eg, cyclophosphamide or chlorambucil], total lymphoid irradiation, etc).
    9. Subjects who have received rituximab or other selective B lymphocyte depleting agents within 1 year prior to baseline.
    10. Subjects previously receiving leukocyte apheresis, including selective lymphocyte, monocyte, or granulocyte apheresis, or plasma exchange within 6 months prior to baseline.
    11. Other marketed immunosuppressants or biologics with immunomodulatory properties within 3 months prior to baseline.
    12. Subjects who have received other JAK inhibitors within 3 months prior to baseline.
    13. Subjects who have not responded to or have been intolerant of other JAK inhibitors.

    14. Other investigational procedures(s) or product(s), such as immunosuppressants used in transplantation (eg, mycophenolate mofetil, cyclosporine, rapamycin, or tacrolimus) or live (attenuated) vaccine within 30 days prior to baseline.

        14) Subjects with history of thrombotic event(s), including deep venous thrombosis (DVT), and known inherited conditions that predispose to hypercoagulability.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-06700841 or placebo	Drug: Placebo PF-06700841; 12 weeks, followed by PF-06700841, 30 mg QD for 52 weeks; Drug: PF-06700841; 60 mg QD for 12 weeks followed by 30 mg QD for up to 52 weeks
Experimental: PF-06651600 or placebo	Drug: PF-06651600 Placebo; 12 weeks, followed by PF-06651600, 50 mg once daily (QD) for 52 weeks; Drug: PF-06651600; 200 mg QD for 8 weeks, followed by 50 mg QD up to 56 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Greater Than or Equal to (>=) 50 Percent (%) Reduction in Simple Endoscopic Score for Crohn's Disease (SES CD50) at Week 12: Induction Period	SES CD50 was defined as 50% improvement from baseline in SES-CD. Baseline was defined as last measurement prior to first dosing on Day 1. Following bowel segments were used for calculating SES-CD scores: Ileum, right colon(C), transverse C, left C and rectum. Each segment assessed for four domains: presence of ulcers, ulcerated surface, affected surface and presence of narrowing, each scored on a scale of 0 to 3, higher scores indicated more severe condition. Presence of ulcers score: 0=none, 1=small ulcer: (0.1-0.5 centimeter[cm]), 2=Large ulcer(0.5-2 cm), 3=very large ulcer(>2 cm); ulcerated surface score: 0=none, 1=<10%, 2=10-30% and 3=>30%; affected surface score: 0=unaffected segment, 1=<50%, 2=50-75% and 3=>75%; presence of narrowing score: 0=none,1=single, can be passed, 2=multiple, can be passed and 3=cannot be passed. Total SES CD score was determined by sum of each domain score for all 5 bowel segments and ranged from 0 to 60, higher score indicating more severe disease.	Week 12
Number of Participants With Laboratory Test Abnormalities During OLE Period	Pre-specified criteria for lab abnormalities included- hematology: hemoglobin(Hb), erythrocytes (ery),hematocrit:<0.8*lower limit of normal(LLN);reticulocytes: <0.5*LLN, >1.5*upper limit of normal(ULN); ery mean corpuscular(EMC) volume: <0.9*ULN, >1.11*ULN;EMC Hb: <0.9*LLN; platelets:>1.75*ULN; leukocytes(10^9/L): <0.6*LLN,>1.5*ULN;lymphocyte,neutrophil(10^9/L):<0.8*LLN,>1.2*ULN;basophil,eosinophil,monocyte(10^9/L):>1.2*ULN;activated partial thromboplastin time (sec): >1.1*ULN. Chemistry: bilirubin(mg/dL),aspartate aminotransferase(AT),alanine AT(units per litre)>3.0*ULN; protein, albumin(g/dL):<0.8*LLN; creatinine, triglycerides (mg/dL):>1.3*ULN; urate(mg/dL):>1.2*ULN, potassium (mEq/L):<0.9*LLN; calcium (mg/dL): <0.9*LLN,>1.1*ULN. Urinalysis: pH>8;urine,glucose,protein(mg/dl); ketones, nitrite, urine Hb(scalar):>=1. Number of participants with any lab abnormality meeting pre-specified criteria are reported.	From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
Number of Participants According to Categorization of Vital Signs During OLE Period	Vital signs including blood pressure (diastolic blood pressure [DBP], systolic blood pressure [SBP], and pulse rate [PR]) were measured in a supine position using automated devices. DBP included value < 50 (millimeter of mercury [mmHg]), change >=20 (mmHg) increase and change >=20 (mmHg) decrease; SBP: value < 90 (mmHg), change >= 30 (mmHg) increase and change >= 30 (mmHg) decrease; PR: value > 120 (beats per minute [bpm]).	From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
Number of Participants With Abnormal Clinically Significant Electrocardiogram Findings During OLE Period	Single twelve lead ECGs were obtained using an automated ECG machine after participant had rested quietly for at least 10 minutes in a supine position. QTc prolongations were defined as a QTc >=480 milli second (msec) or an absolute change in QTc greater than (>) 60 msec. Clinically significant ECG findings were determined by the investigator.	From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During OLE Period	An adverse event (AE) was any untoward medical occurrence in a study participant administered a study intervention; the event need not necessarily have a causal relationship with the treatment or usage. An AE was considered TEAE to a given treatment if the event started during the effective duration of treatment regardless of whether a similar event of equal or greater severity existed in the baseline period.	From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
Number of Participants With Treatment Emergent Serious Adverse Events (TESAE) During OLE Period	A serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions) or resulted in congenital anomaly/birth defect or was considered an important medical event. An SAE was considered as TESAE if the event started during the effective duration of treatment regardless of whether a similar event of equal or greater severity existed in the baseline period.	From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)
Number of Participants With Discontinuations Due to Adverse Events During OLE Period	An AE was any untoward medical occurrence in a study participant administered a study intervention; the event need not necessarily have a causal relationship with the treatment or usage. Discontinuations from study due to TEAEs were defined as participants with an AE record indicating the AE caused permanent discontinuation from the study but action taken with study treatment was not drug withdrawn. Permanent discontinuations from any study intervention due to TEAEs were defined as participants with an AE record indicating that action taken with study treatment was drug withdrawn. In this outcome measure number of participants with discontinuation from study due to AEs and permanent discontinuation from study intervention due to AEs are reported.	From start of study intervention in OLE period up to 4 weeks after last dose of study intervention (up to 56 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Laboratory Test Abnormalities During Induction Period	Pre-specified criteria for lab abnormalities included- hematology: hemoglobin, erythrocytes, hematocrit:<0.8*LLN; reticulocytes: <0.5*LLN, >1.5*ULN; EMC volume: <0.9*ULN, >1.11*ULN;EMC Hb: <0.9*LLN; platelets:>1.75*ULN; leukocytes(10^9/L): <0.6*LLN, >1.5*ULN; lymphocyte, neutrophil(10^9/L):<0.8*LLN, >1.2*ULN; basophil, eosinophil, monocyte(10^9/L):>1.2*ULN; activated partial thromboplastin time (sec): >1.1*ULN. Chemistry: bilirubin(mg/dL),aspartate aminotransferase(AT),alanine AT(units per litre)>3.0*ULN; protein, albumin(g/dL):<0.8*LLN; creatinine, triglycerides (mg/dL):>1.3*ULN; urate(mg/dL):>1.2*ULN, potassium (mEq/L):<0.9*LLN; calcium (mg/dL): <0.9*LLN,>1.1*ULN. Urinalysis: pH>8; urine, glucose, protein(mg/dl); ketones, nitrite, urine Hb(scalar):>=1. Number of participants with any lab abnormality meeting pre-specified criteria are reported.	From start of study intervention on Day 1 up to Week 12
Number of Participants According to Categorization of Vital Signs During Induction Period	Vital signs including blood pressure (diastolic blood pressure [DBP], systolic blood pressure [SBP], and pulse rate [PR]) were measured in a supine position using automated devices. DBP included value < 50 (mmHg), change >=20 (mmHg) increase and change >=20 (mmHg) decrease; SBP: value < 90 (mmHg), change >= 30 (mmHg) increase and PR: value > 120 (bpm).	From start of study intervention on Day 1 up to Week 12
Number of Participants With Abnormal Clinically Significant Electrocardiogram Findings During Induction Period	Single twelve lead ECGs were obtained using an automated ECG machine after participant had rested quietly for at least 10 minutes in a supine position. QTc prolongations were defined as a QTc greater than or equal to (>=)480 milli second (msec) or an absolute change in QTc greater than (>)60 msec. Clinically significant ECG findings were determined by the investigator.	From start of study intervention on Day 1 up to Week 12
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During Induction Period	An AE was any untoward medical occurrence in a study participant administered a study intervention; the event need not necessarily have a causal relationship with the treatment or usage. An AE was considered TEAE to a given treatment if the event started during the effective duration of treatment regardless of whether a similar event of equal or greater severity existed in the baseline period.	From start of study intervention on Day 1 up to Week 12
Number of Participants With Treatment Emergent Serious Adverse Events (TESAE) During Induction Period	A SAE was any untoward medical occurrence at any dose that: resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions) or resulted in congenital anomaly/birth defect or was considered an important medical event. An SAE was considered as TESAE if the event started during the effective duration of treatment regardless of whether a similar event of equal or greater severity existed in the baseline period.	From start of study intervention on Day 1 up to Week 12
Number of Participants Discontinuation Due to Adverse Events During Induction Period	An AE was any untoward medical occurrence in a study participant administered a study intervention; the event need not necessarily have a causal relationship with the treatment or usage. Discontinuations from study due to TEAEs were defined as participants with an AE record indicating the AE caused permanent discontinuation from the study but action taken with study treatment was not drug withdrawn. Permanent discontinuations from any study intervention due to TEAEs were defined as participants with an AE record indicating that action taken with study treatment was drug withdrawn. In this outcome measure number of participants with discontinuation from study due to AEs and permanent discontinuation from study intervention due to AEs are reported.	From start of study intervention on Day 1 up to Week 12
Number of Participants With Serious Infections During Induction Period	Participants were monitored for development of any infection (viral, bacterial and fungal). Serious infections were treated infections that required parenteral antimicrobial therapy and were present with positive pre-treatment culture and required hospitalization for treatment/met other criteria that required the infection to be classified as SAE. An SAE was any untoward medical occurrence at any dose that: resulted in death; is life-threatening; requires inpatient hospitalization/prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity/results in congenital anomaly/birth defect. Treated infections were infections that required antimicrobial therapy by any route of administration/required any surgical intervention (e.g., incision and drainage).	From start of study intervention on Day 1 up to Week 12
Percentage of Participants Who Achieved Clinically Meaningful Endoscopic Improvement (CMEI) (Reduction of >=3 Points From Baseline in SES-CD Score) at Week 12: Induction Period	CMEI was defined as reduction of >=3 points from baseline in SES-CD score as assessed by centrally read SES-CD score. Baseline: last measurement prior to first dosing on Day1. Following bowel segments were used for calculating SES-CD scores: Ileum, right C, transverse C, left C and rectum. Each segment assessed for 4 domains: presence of ulcers, ulcerated surface, affected surface and presence of narrowing, each scored on scale of 0-3, higher scores indicated more severe condition. Presence of ulcers score: 0=none,1=small ulcer: (0.1-0.5cm),2=Large ulcer(0.5-2cm),3=very large ulcer(>2cm); ulcerated surface score: 0=none,1=<10%,2=10-30% and 3=>30%; affected surface score: 0=unaffected segment, 1=<50%, 2=50-75% and 3=>75%; presence of narrowing score: 0=none,1=single, can be passed, 2=multiple, can be passed and 3=cannot be passed. Total SES CD score was determined by sum of each domain score for all 5 bowel segments and ranged from 0 to 60, higher score indicating more severe disease.	Week 12
Mean Change From Baseline in SES-CD Score at Week 12: Induction Period	Mean change from baseline in SES-CD score at Week 12 analyzed using analysis of covariance(ANCOVA)model with treatment,baseline disease activity/extent as factors, baseline SES CD score as covariate. Baseline=last measurement prior to first dosing on Day 1. Following bowel segments used for calculating SES-CD scores: Ileum,right C,transverse C,left C,rectum. Each segment assessed for four domains:presence of ulcers, ulcerated surface, affected surface,presence of narrowing, each score on a scale of 0-3,higher scores=more severe condition. Presence of ulcers score:0=none,1=small ulcer:(0.1-0.5cm),2=large ulcer(0.5-2cm),3=very large ulcer(>2 cm);ulcerated surface score:0=none,1=<10%,2=10-30%,3=>30%;affected surface score:0=unaffected segment,1=<50%, 2=50-75%,3=>75%;presence of narrowing score:0=none,1=single,can be passed,2=multiple can be passed,3=cannot be passed. Total SES CD score=sum of each domain score for all 5 bowel segments,range from 0 to 60,higher score =more severe disease.	Baseline and Week 12
Percentage of Participants Achieving >=25% Reduction in SES-CD From Baseline (SES-CD 25) at Week 12: Induction Period	SES CD25 was defined as >=25% improvement from baseline in SES CD. Baseline was defined as the last measurement prior to first dosing on Day 1. Following bowel segments were used for calculating SES-CD scores: Ileum, right C, transverse C, left C and rectum. Each segment assessed for four domains: presence of ulcers, ulcerated surface, affected surface and presence of narrowing, each scored on a scale of 0 to 3, higher scores indicated more severe condition. Presence of ulcers score: 0=none, 1=small ulcer: (0.1-0.5 centimeter[cm]), 2=Large ulcer(0.5-2 cm), 3=very large ulcer(>2 cm); ulcerated surface score: 0=none, 1=<10%, 2=10-30% and 3=>30%; affected surface score: 0=unaffected segment, 1=<50%, 2=50-75% and 3=>75%; presence of narrowing score: 0=none,1=single, can be passed, 2=multiple, can be passed and 3=cannot be passed. Total SES CD score was determined by sum of each domain score for all 5 bowel segments and ranged from 0 to 60, higher score indicating more severe disease.	Week 12
Percentage of Participants Achieving Endoscopic Remission (SES-CD Score of <= 2) at Week 12: Induction Period	Endoscopic remission was defined as SES-CD score of <= 2. Following bowel segments were used for calculating SES-CD scores: Ileum, right colon(C), transverse C, left C and rectum. Each segment assessed for four domains: presence of ulcers, ulcerated surface, affected surface and presence of narrowing, each scored on a scale of 0 to 3, higher scores indicated more severe condition. Presence of ulcers score: 0=none, 1=small ulcer: (0.1-0.5 centimeter[cm]), 2=Large ulcer(0.5-2 cm), 3=very large ulcer(>2 cm); ulcerated surface score: 0=none, 1=<10%, 2=10-30% and 3=>30%; affected surface score: 0=unaffected segment, 1=<50%, 2=50-75% and 3=>75%; presence of narrowing score: 0=none,1=single, can be passed, 2=multiple, can be passed and 3=cannot be passed. Total SES CD score was determined by sum of each domain score for all 5 bowel segments and ranged from 0 to 60, higher score indicating more severe disease.	Week 12
Percentage of Participants Achieving Mucosal Healing at Week 12: Induction Period	Mucosal healing was defined as complete absence of ulcers.	Week 12
Percentage of Participants Achieving CMEI at Week 64 Among Participants Who Achieved CMEI Response at Week 12 (Baseline of OLE Period): OLE Period	CMEI was defined as reduction of >=3 points from baseline as assessed by centrally read SES CD score. Baseline: last measurement prior to first dosing on Day 1 of Week 12. Following bowel segments were used for calculating SES-CD scores: Ileum, right C, transverse C, left C and rectum. Each segment assessed for four domains: presence of ulcers, ulcerated surface, affected surface and presence of narrowing, each scored on scale of 0-3, higher scores indicated more severe condition. Presence of ulcers score: 0=none,1=small ulcer: (0.1-0.5 cm),2=Large ulcer(0.5-2 cm),3=very large ulcer(>2 cm); ulcerated surface score: 0=none,1=<10%, 2=10-30% and 3=>30%; affected surface score: 0=unaffected segment, 1=<50%, 2=50-75% and 3=>75%; presence of narrowing score: 0=none,1=single, can be passed, 2=multiple, can be passed and 3=cannot be passed. Total SES CD score was determined by sum of each domain score for all 5 bowel segments and ranged from 0-60, higher score indicating more severe disease.	Week 64 (Week 52 of OLE period)
Percentage of Participants Achieving SES CD 25 and SES CD 50 at Week 64 Among Participants Who Achieved SES CD 25 and SES CD 50 at Week 12 (Baseline of OLE Period): OLE Period	SES CD50 and SES CD25: 50% and 25% improvement from baseline, respectively. Baseline: last measurement prior to first dosing on Day 1 of Week 12. Following bowel segments were used for calculating SES-CD scores: Ileum, right C, transverse C, left C and rectum. Each segment assessed for four domains: presence of ulcers, ulcerated surface, affected surface and presence of narrowing, each scored on a scale of 0 to 3, higher scores indicated more severe condition. Presence of ulcers score: 0=none, 1=small ulcer: (0.1-0.5 cm), 2=Large ulcer(0.5-2 cm), 3=very large ulcer(>2 cm); ulcerated surface score: 0=none, 1=<10%, 2=10-30% and 3=>30%; affected surface score: 0=unaffected segment, 1=<50%, 2=50-75% and 3=>75%; presence of narrowing score: 0=none,1=single, can be passed, 2=multiple, can be passed and 3=cannot be passed. Total SES CD score was determined by sum of each domain score for all 5 bowel segments and ranged from 0 to 60, higher score indicating more severe disease.	Week 64 (Week 52 of OLE period)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

General Publications

• Fensome A, Ambler CM, Arnold E, Banker ME, Brown MF, Chrencik J, Clark JD, Dowty ME, Efremov IV, Flick A, Gerstenberger BS, Gopalsamy A, Hayward MM, Hegen M, Hollingshead BD, Jussif J, Knafels JD, Limburg DC, Lin D, Lin TH, Pierce BS, Saiah E, Sharma R, Symanowicz PT, Telliez JB, Trujillo JI, Vajdos FF, Vincent F, Wan ZK, Xing L, Yang X, Yang X, Zhang L. Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases: Discovery of (( S)-2,2-Difluorocyclopropyl)((1 R,5 S)-3-(2-((1-methyl-1 H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF-06700841). J Med Chem. 2018 Oct 11;61(19):8597-8612. doi: 10.1021/acs.jmedchem.8b00917. Epub 2018 Aug 16.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2018
• Primary Completion (Actual): October 19, 2023
• Study Completion (Actual): October 19, 2023

Study Registration Dates

• First Submitted: December 5, 2017
• First Submitted That Met QC Criteria: January 3, 2018
• First Posted (Actual): January 10, 2018

Study Record Updates

• Last Update Posted (Actual): October 30, 2024
• Last Update Submitted That Met QC Criteria: October 7, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; PF-06700841
• Other Study ID Numbers: B7981007; 2017-003359-43 (EudraCT Number); PIZZICATO (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No