Phase 2a, Dose-ranging Study With PF-05221304 in Nonalcoholic Fatty Liver Disease (NAFLD)

A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-RANGING, PARALLEL GROUP STUDY TO EVALUATE SAFETY, TOLERABILITY, AND PHARMACODYNAMICS OF PF-05221304 ADMINISTERED DAILY FOR 16-WEEKS TO ADULT SUBJECTS WITH NONALCOHOLIC FATTY LIVER DISEASE

Phase 2a, dose-ranging Study with PF-05221304 in Nonalcoholic Fatty Liver Disease (NAFLD)

Study Overview

• Status: Completed
• Conditions: Nonalcoholic Fatty Liver Disease; Nonalcoholic Steatohepatitis
• Intervention / Treatment: Drug: Placebo; Drug: PF-05221304

Detailed Description

A Phase 2a, Randomized, Double-blind, Placebo-controlled, Dose-ranging, Parallel Group Study To Evaluate Safety, Tolerability, And Pharmacodynamics Of PF-05221304 Administered Daily For 16-weeks To Adult Subjects With Nonalcoholic Fatty Liver Disease

• Study Type: Interventional
• Enrollment (Actual): 305
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Maroubra, New South Wales, Australia, 2035
      • Australian Clinical Research Network
    • Randwick, New South Wales, Australia, 2013
      • Spectrum Medical Imaging
    • Westmead, New South Wales, Australia, 2145
      • Castlereagh Imaging
    • Westmead, New South Wales, Australia, 2145
      • Storr Liver Centre, Westmead Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Dr. Jones & Partners Medical Imaging
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital, Department of Gastroenterology and Hepatology
    • Adelaide, South Australia, Australia, 5042
      • Flinders Medical Centre/Department of Gastroenterology & Hepatology
    • Adelaide, South Australia, Australia, 5067
      • Radiology SA
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Canada
  • Quebec, Canada, G3K 2P8
    • ALPHA Recherche Clinique
  • Quebec, Canada, G1W 4R4
    • Centre de Recherche Saint-Louis
  • Quebec, Canada, G1J0H4
    • IRM Quebec
  • Quebec, Canada, G1J5B9
    • IRM Quebec
  • Quebec, Canada, G1V 4G2
    • CHU de Quebec - Universite Laval - site Centre Hospitalier de l'Universite Laval (CHUL)
  • Quebec, Canada, G1V 4G5
    • Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
  • Quebec, Canada, G1W 4R4
    • IRM Québec - Clinique St-Louis
  • Quebec, Canada, G3K 2P8
    • Clinix
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1H2
      • Lair Centre
    • Vancouver, British Columbia, Canada, V5Y 3W2
      • Dr TG Elliott Inc - BC Diabetes
    • Vancouver, British Columbia, Canada, V5Z 1C6
      • False Creek Healthcare Centre
    • Vancouver, British Columbia, Canada, V5Z 1C6
      • False Creek Healthcare
    • Victoria, British Columbia, Canada, V8T 5G4
      • Discovery Clinical Services Ltd.
    • Victoria, British Columbia, Canada, V8Z 0B9
      • West Coast Medical Imaging
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Nova Scotia Health Authority, QEII Health Sciences Centre
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Nova Scotia Health Authority, QEII Health Sciences Centre
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • Nova Scotia Health Authority - QEII Health Sciences Centre
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Aggarwal and Associates Limited
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre - University Hospital
    • London, Ontario, Canada, N6A 4V2
      • St. Joseph's Health Care London
    • Mississauga, Ontario, Canada, L5R 3K7
      • Oxford Medical Imaging
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M4G 3E8
      • LMC Clinical Research Inc. (Bayview)
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital - MRI Research Centre
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network (UHN) - Toronto General Hospital - Toronto Centre for Liver Disease (TCLD)
    • Toronto, Ontario, Canada, M5G 2C4
      • University of Toronto - Toronto General Hospital
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network (UHN)
    • Toronto, Ontario, Canada, M6H 3M1
      • Toronto Liver Centre - Liver Care Centre Corporation
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 7K9
      • Ecogene-21
    • Chicoutimi, Quebec, Canada, G7H 4J1
      • Resonance Magnetique du Saguenay-Lac-Saint-Jean
    • Montreal, Quebec, Canada, H2X 0A9
      • Centre de recherche du CHUM
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre
    • Montreal, Quebec, Canada, H4A 3J1
      • Research Institute of the MUHC
    • Montreal, Quebec, Canada, H2K 1H2
      • Medpharmgene Inc
    • Montreal, Quebec, Canada, H2L 4E9
      • Clinique de médecine Urbaine du Quartier Latin
    • Montreal, Quebec, Canada, H4A 3J1
      • Cedar Cancer Center - McGill University Health Centre
    • Montreal, Quebec, Canada, H4A 3J1
      • Chronic Viral Illness Service - Royal Victoria Hospital - McGill University Health Centre (MUHC)
    • Montreal, Quebec, Canada, H5B 1B2
      • Radiologie Varad
    • Sherbrooke, Quebec, Canada, J1G 2E8
      • Centre Intégré Universitaire de Santé et de Services Sociaux (CIUSSS) de l'Estrie
    • St-Jerome, Quebec, Canada, J7Z 5T3
      • Recherche Médicale St-Jérôme Inc
• Israel
  • Hadera, Israel, 3810101
    • Hillel Yaffe Medical Center
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
  • Haifa, Israel, 3434104
    • Lady Davis Carmel Medical Center
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center
  • Jerusalem, Israel, 9112001
    • Hadassah Hebrew University Medical Center - Ein Kerem
  • Nahariya, Israel, 2210001
    • Galilee Medical Center
  • Nazareth, Israel, 1610001
    • Holy Family Hospital
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center
  • Ramat-Gan, Israel, 5265601
    • The Chaim Sheba Medical Center
  • Tel-Aviv, Israel, 6423906
    • Tel-Aviv Sourasky Medical Center
• Poland
  • Bialystok, Poland, 15-879
    • ClinicMed Badurski i Wspolnicy Spolka Jawna
  • Gdansk, Poland, 80-546
    • Centrum Badan Klinicznych PI-House Sp. z o.o.
  • Gdansk, Poland, 80-382
    • Synexus Polska Sp. z o.o. Oddzial w Gdansku
  • Gdynia, Poland, 81-537
    • Synexus Polska Sp. z o.o. Oddzial w Gdyni
  • Jaworze, Poland, 43-384
    • Osrodek Badan Klinicznych
  • Katowice, Poland, 40-040
    • Synexus Polska Sp. Z O.O. Oddzial W Katowicach
  • Katowice, Poland, 40-282
    • Silmedic Sp. z o.o. Oddzial w Katowicach
  • Krakow, Poland, 31-501
    • Krakowskie Centrum Medyczne Sp. z o.o.
  • Krakow, Poland, 31-315
    • Centrum Medyczne A-Z Clinic
  • Lodz, Poland, 90-132
    • Gabinet Lekarski Malgorzata Saryusz-Wolska
  • Poznan, Poland, 60-702
    • Synexus Polska Sp. z o.o Oddzial w Poznaniu
  • Rzeszow, Poland, 35-326
    • Centrum Medyczne Medyk
  • Warszawa, Poland, 01-192
    • Synexus Polska Sp. z o. o. Oddzial w Warszawie
  • Wroclaw, Poland, 50-381
    • Synexus Polska Sp. z o.o. Oddzial we Wroclawiu
  • Wroclaw, Poland, 50-349
    • Niepubliczny Zaklad Opieki Zdrowotnej Centrum Badan Klinicznych
  • Wroclaw, Poland, 53-301
    • DOBROSTAN - Gabinety Lekarskie
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Chung-Ho Memorial Hospital, Kaohsiung Medical University
  • Tainan, Taiwan, 704
    • National Cheng-Kung University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Changhua County
    • Changhua city, Changhua County, Taiwan, 500
      • Changhua Christian Hospital
• United States
  • California
    • Bakersfield, California, United States, 93301
      • Franco Felizarta MD
    • Chula Vista, California, United States, 91911
      • eStudySite
    • Chula Vista, California, United States, 91911
      • San Diego Imaging Chula Vista
    • La Jolla, California, United States, 92037
      • University of California, San Diego
    • La Jolla, California, United States, 92037
      • University of California, San Diego (Altman Clinical and Translational Research Institute)
    • La Mesa, California, United States, 91942
      • eStudySite
    • Lincoln, California, United States, 95648
      • Clinical Trials Research
    • Los Angeles, California, United States, 90057
      • National Research Institute
    • Palo Alto, California, United States, 94304
      • Stanford University Medical Center
    • Palo Alto, California, United States, 04304
      • Stanford University Medical Center, Blake wilbur Building
    • Pasadena, California, United States, 91105
      • Huntington Medical Research Institute
    • Rialto, California, United States, 92377
      • Inland Empire Liver Foundation
    • San Diego, California, United States, 92114
      • Precision Research Institute
    • San Francisco, California, United States, 94115
      • Quest Clinical Research
  • Colorado
    • Englewood, Colorado, United States, 80113
      • South Denver Gastroenterology, P.C.
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Jacksonville, Florida, United States, 32256
      • Borland-Groover Clinic
    • Miami, Florida, United States, 33136
      • Schiff Center for Liver Diseases/University of Miami
    • Miami, Florida, United States, 33145
      • Stand Up MRI of Miami
    • Miami Springs, Florida, United States, 33166
      • Ocean Blue Medical Research Center, Inc
    • Orange City, Florida, United States, 32763
      • Avail Clinical Research, LLC
    • Orlando, Florida, United States, 32806
      • Bioclinica Research
    • Palm Harbor, Florida, United States, 34684
      • Advanced Gastroenterology Associates, LLC
    • South Miami, Florida, United States, 33143
      • Qps-Mra, Llc
    • Tampa, Florida, United States, 33612
      • University of South Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Medical Group
    • Wellington, Florida, United States, 33414
      • South Florida Center of Gastroenterology, PA
    • Wellington, Florida, United States, 33449
      • Independent Imaging
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
    • Honolulu, Hawaii, United States, 96814
      • Invision Imaging
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Midwest Institute for Clinical Research
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Imaging at St. Francis
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
    • Catonsville, Maryland, United States, 21228
      • Digestive Disease Associates, PA
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic- Main Campus
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Gastrointestinal Associates, PA
    • Jackson, Mississippi, United States, 39202
      • Colonnades at Baptist
  • New York
    • Rochester, New York, United States, 14623
      • BioTelemetry Research
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • The University of NC at Chapel Hill, Clinical and Translational Research Center (CTRC)
    • Chapel Hill, North Carolina, United States, 27514
      • Investigational Drug Service, University of North Carolina Hospitals
    • Chapel Hill, North Carolina, United States, 27599
      • The University of North Carolina at Chapel Hill, Biomedical Research Imaging Center (MRI Facility)
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington, LLC
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research, Inc.
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Sterling Research Group, Ltd.
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • ClinSearch
    • Chattanooga, Tennessee, United States, 37404
      • Prime Imaging (Chattanooga Outpatient Center)
  • Texas
    • Austin, Texas, United States, 78705
      • Touchstone
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine - Advanced Liver Therapies
    • Rollingwood, Texas, United States, 78746
      • Pinnacle Clinical Research
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.
    • San Antonio, Texas, United States, 78229
      • Pinnacle Clinical Research, PLLC
  • Utah
    • Layton, Utah, United States, 84041
      • Clinical Research Advantage, Inc./Wasatch Peak Family Practice
  • Virginia
    • Richmond, Virginia, United States, 23294
      • National Clinical Research - Richmond, Inc.
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body Mass Index >= 25 kg/m2
• Body Weight > 50 kg
• Liver fat (assessed via MRI-PDFF) >= 8%
• Biopsy-proven NASH - diagnosed in previous 24-months
• Presumed NASH - per Sponsor's definition
• NAFLD with minimal inflammation/fibrosis
• Features of Metabolic Syndrome

Exclusion Criteria:

• Alcohol-induced steatohepatitis or other forms of chronic liver disease
• Positive for Hepatitis B, Hepatitis C, or Human Deficiency Virus
• Severe Renal Impairment
• Contraindications for MRI

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Double-Blind, PF-05221304-matching Placebo	Drug: Placebo; Placebo
Active Comparator: PF-05221304 - 2 mg; PF-05221304 - 2 mg, once-daily	Drug: PF-05221304; PF-05221304, Experimental Drug
Active Comparator: PF-05221304 - 10 mg; PF-05221304 - 10 mg, once-daily	Drug: PF-05221304; PF-05221304, Experimental Drug
Active Comparator: PF-05221304 - 25 mg; PF-05221304 - 25 mg, once-daily	Drug: PF-05221304; PF-05221304, Experimental Drug
Active Comparator: PF-05221304 - 50 mg; PF-05221304 - 50 mg, once-daily	Drug: PF-05221304; PF-05221304, Experimental Drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Liver Fat by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI- PDFF) at Week 16	MRI-PDFF utilized a gradient echo sequence with low flip angle (FA) to minimize T1 bias, corrected T2* decay (due to iron overload) via modeling of the fat signal as a superposition of multiple frequency components from 5 different lipid types, and was applied in each of the 9 Couinaud segments. This technique improved fat quantification accuracy for the entire liver permitting quantification of small differences/changes following pharmacological intervention.	Baseline (between Day -14 and Day 1), Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Alanine Aminotransferase at Week 16	Potential improvement in liver function was denoted by reduction in alanine transaminase (ALT)	Baseline (Day 1 pre-dose), Week 16
Number of Participants With Treatment-Emergent Adverse Events	An AE was any untoward medical occurrence in a study subject administered a product or medical device. A serious AE (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Any such events with initial onset or increasing in severity after the first dose of study treatment were counted as treatment-emergent.	From first dose of study treatment (Day 1) up to Week 20
Number of Participants With Laboratory Abnormalities	Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (hemoglobin, hematocrit, erythrocytes, reticulocytes, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, prothrombin time [PT], PT/international normalized ratio, reticulocytes); chemistry (indirect bilirubin, direct bilirubin, protein, albumin, blood urea nitrogen, creatinine, creatine kinase, urate, calcium, sodium, potassium, chloride, bicarbonate, urine urobilinogen); urinalysis (pH, urine glucose, urine ketones, urine protein, urine hemoglobin, nitrites, leukocyte esterase, urine erythrocytes, urine leukocytes, urine hyaline casts, urine bilirubin, granular casts).	From first dose of study treatment (Day 1) up to Week 20
Number of Participants With Vital Signs Data Meeting Predefined Criteria	Vital signs categorical summarization criteria: 1) sitting systolic blood pressure (SBP) <90 or >180 millimeters of mercury (mmHg); 2) sitting diastolic blood pressure (DBP) <50 mmHg or >110 mmHg; 3) sitting pulse rate <40 or >120 beats per minute (bpm); 4) change from baseline (increase or decrease) in sitting DBP greater than or equal to (>=) 20 mmHg; 5) change from baseline (increase or decrease) in sitting SBP >=30 mmHg.	From first dose of study treatment (Day 1) up to Week 18
Number of Participants With 12-Lead Electrocardiogram (ECG) Data Meeting Predefined Criteria	ECG categorical summarization criteria: 1) QRS interval (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization) >=140 milliseconds (msec); 2) QRS interval >=50% change from baseline; 3) PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization) >=300 msec; 4) PR interval >=25% change when baseline is >200 msec or >=50% change when baseline is <=200 msec; 5) QT interval (time from ECG Q wave to the end of the T wave corresponding to electrical systole): absolute value of >=500 msec; 6) QTcF interval (QT corrected for heart rate using Fridericia's formula) absolute value of 450 to <480 msec; 7) QTcF interval: absolute value of 480 to <500 msec; 8) QTcF interval: absolute value >=500 msec; 9) QTcF interval: a change from baseline of 30 to <60 msec; 10) QTcF interval: a change from baseline >=60 msec.	From first dose of study treatment (Day 1) up to Week 18

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Calle RA, Amin NB, Carvajal-Gonzalez S, Ross TT, Bergman A, Aggarwal S, Crowley C, Rinaldi A, Mancuso J, Aggarwal N, Somayaji V, Inglot M, Tuthill TA, Kou K, Boucher M, Tesz G, Dullea R, Bence KK, Kim AM, Pfefferkorn JA, Esler WP. ACC inhibitor alone or co-administered with a DGAT2 inhibitor in patients with non-alcoholic fatty liver disease: two parallel, placebo-controlled, randomized phase 2a trials. Nat Med. 2021 Oct;27(10):1836-1848. doi: 10.1038/s41591-021-01489-1. Epub 2021 Oct 11.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2017
• Primary Completion (Actual): February 26, 2019
• Study Completion (Actual): March 27, 2019

Study Registration Dates

• First Submitted: August 10, 2017
• First Submitted That Met QC Criteria: August 10, 2017
• First Posted (Actual): August 14, 2017

Study Record Updates

• Last Update Posted (Actual): December 9, 2020
• Last Update Submitted That Met QC Criteria: December 7, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: NAFLD; NASH; PF-05221304; features of metabolic syndrome; Dose-Ranging Study
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: C1171002; 2017-001156-55 (EudraCT 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