- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02704429
A Study of PRN1008 in Adult Patients With Pemphigus Vulgaris
An Open-Label, Phase 2, Pilot Study Investigating the Safety, Clinical Activity, Pharmacokinetics, and Pharmacodynamics of Oral Treatment With the BTK Inhibitor PRN1008 in Patients With Newly Diagnosed or Relapsing Pemphigus Vulgaris
Study Overview
Detailed Description
Primary Objectives:
To evaluate the safety of PRN1008 in patients with pemphigus vulgaris (PV)
To evaluate the clinical activity of PRN1008 in patients with PV, per criteria in the European Academy of Dermatology and Venereology (EADV) 2014 Pemphigus S2 Guideline (Hertl et al. 2015)
Secondary Objectives
To evaluate the pharmacokinetics (PK) and the pharmacodynamics (PD) of multiple doses of PRN1008 in patients with PV
To evaluate the relationship of PK and PD to each other and to efficacy and safety in this patient population
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
New South Wales
-
Kogarah, New South Wales, Australia, 2217
- Premier Specialists
-
-
Victoria
-
East Melbourne, Victoria, Australia, 3002
- Sinclair Dermatology
-
Melbourne, Victoria, Australia, 3050
- Royal Melbourne, Dermatology Office
-
-
-
-
-
Osijek, Croatia, 31000
- Clinical Hospital Osijek
-
Zagreb, Croatia, 10 000
- Klinichki Bolnicki Centar Zagreb
-
-
-
-
-
Rouen, France, 76038
- Rouen university hospital
-
-
Siene-Saint Denis
-
Bobigny, Siene-Saint Denis, France, 93009
- Hopital Avicenne
-
-
-
-
-
Athens, Greece, 16121
- Hospital of Venereal and Skin Diseases A.Syggros
-
Thessaloniki, Greece, 56429
- Papageorgiou General Hospital of Thessaloniki
-
-
Ioannina
-
Ioánnina, Ioannina, Greece, 45500
- University General Hospital of Ioannina
-
-
Thessaly
-
Larissa, Thessaly, Greece, 41110
- University Hospital of Larissa
-
-
-
-
-
Ramat-Gan, Israel, 52621
- Chaim Sheba Medical Center
-
Tel Aviv, Israel, 64239
- Tel Aviv Sourasky Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Male or female patients, aged 18 to 80 years old, with biopsy-proven, mild-moderate PV (PDAI 8 to 45) in Part A and mild to severe PV in Part B (PDAI 8 to 60) that are either:
- newly diagnosed patients (i.e. naïve to an effective induction treatment regimen) for whom an initial period of PRN1008 monotherapy is judged clinically acceptable, or
- relapsing patients, for whom an initial period of PRN1008 monotherapy, or combination therapy with any of low dose corticosteroid, ie.0.5 mg/kg of prednis(ol)one per day
Exclusion Criteria:
- Pregnant or lactating women
- A history of malignancy of any type, other than surgically excised non-melanoma skin cancers or in situ cervical cancer within 5 years before the day of dosing
- Use of immunologic response modifiers with the following periods prior to Day 1: 1 week: cyclophosphamide; 4 weeks: intravenous immunoglobulin, Kinaret (anakinra) and Enbrel (etanercept); 12 weeks: Remicade (infliximab), Humira (adalimumab), Simponi (golimumab), Orencia (abatacept), Actemra (tocilizumab), Cimzia (certolizumab), Cosentyx (secukinumab), plasmapheresis; 6 months: Rituxan/MabThera (rituximab), ofatumumab, any other anti-CD20 antibody, other long acting biologics
- More than 0.5 mg/kg of prednis(ol)one per day ("low dose corticosteroids") within the two weeks prior to Day 1
- Use of proton pump inhibitor drugs such as omeprazole and esomeprazole
- Has received any investigational drug (or is currently using an investigational device) within the 30 days before receiving the first dose of study medication, or at least 5 times the respective elimination half-life time (whichever is longer)
- History of drug abuse within the precious 12 months
- Alcoholism or excessive alcohol use, defined as regular consumption of more than approximately 3 standard drinks per day
- Refractory nausea and vomiting, malabsorption, external biliary shunt, significant bowel resection that would preclude adequate study drug absorption
- History of anorexia nervosa or periods of three months or more of low body weight in the past 5 years
- Donation of a unit or more of blood or blood products within 4 weeks prior to Day 1
- History of solid organ transplant
- History of epilepsy or other forms of seizures in the last 5 years
- Positive for screening for human immunodeficiency virus, hepatitis B (surface and core antibodies unrelated to vaccination), or hepatitis C (anti-HCV antibody confirmed with Hep C RNA)
- History of active or latent tuberculosis (TB) infection (must test negative using the QuantiFERON test to be eligible)
- History of serious infections requiring intravenous (by catheter that delivers antibiotics into your blood) treatment
- Live vaccine within 28 days prior to baseline or plan to receive one during the study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: PRN1008
Part A: Open-label PRN1008, 12 weeks; 12 weeks follow-up; Part B: Open-label PRN1008, 24 weeks; 4 weeks follow-up
|
Part A dosing was initiated administering 400 mg BID. Intrapatient dose adjustments (reductions and increases) were permitted based upon tolerability and clinical response with the maximum dose allowed up to 600 mg BID for 12 weeks. Part B initial dosing was 400 mg QD for 2 weeks with dose escalation to 400 mg BID at the discretion of the Investigator for the purposes of investigating dose response and identifying the minimal efficacious dose of rilzabrutinib for 24 weeks.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Treatment-emergent Adverse Events
Time Frame: Part A: until 24 weeks and Part B: until 28 weeks
|
Treatment-emergent adverse events (TEAEs) including clinically significant changes in physical examination, laboratory tests, and vital signs.
An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment.
TEAEs were defined as AEs that developed or worsened or became serious during on-treatment phase that was defined as the time from the start of study drug up to study completion.
|
Part A: until 24 weeks and Part B: until 28 weeks
|
Percentage of Participants Who Are Able to Achieve Control of Disease Activity (CDA) Within 4 Weeks of Starting PRN1008 Treatment Without the Need for Doses of Prednisone or Prednisolone >0.5 mg/kg
Time Frame: 4 weeks
|
CDA was defined as the time at which new lesions cease to form and established lesions begin to heal.
|
4 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants Able to Achieve Control of Disease Activity (CDA) Without Corticosteroids Within 4 Weeks
Time Frame: 4 weeks
|
CDA was defined as the time at which new lesions cease to form and established lesions begin to heal.
|
4 weeks
|
Percentage of Participants Able to Achieve a Complete Response (CR) Without Corticosteroids
Time Frame: Part A: 12 weeks treatment and Part B: 24 weeks treatment
|
CR was defined as complete healing of all lesions and the absence of new lesions.
|
Part A: 12 weeks treatment and Part B: 24 weeks treatment
|
Percentage of Participants Able to Achieve Complete Remission (CR) Without the Need for Doses of Prednisone or Prednisolone of Greater Than 0.5mg/kg
Time Frame: Part A: 12 weeks treatment and Part B: 24 weeks treatment
|
CR was defined as complete healing of all lesions and the absence of new lesions.
|
Part A: 12 weeks treatment and Part B: 24 weeks treatment
|
Time to Control of Disease Activity (CDA)
Time Frame: Part A: until 24 weeks and Part B: until 28 weeks
|
CDA was defined as the time at which new lesions cease to form and established lesions begin to heal.
Kaplan-Meier estimate median time is reported.
|
Part A: until 24 weeks and Part B: until 28 weeks
|
Time to End of Consolidation Phase (ECP)
Time Frame: Part A: until 24 weeks and Part B: until 28 weeks
|
ECP was defined as the time at which no new lesions have developed for minimum of 2 weeks, and approximately 80% of existing lesions have healed.
The median time to ECP was based on Kaplan-Meier estimate which considered censoring at end of follow-up for patients who didn't have an event.
A +/-3 days window for visits at Week 3 and 5, and +/-7 days window for visits at Week 9, 13, 17, 21, 25.
|
Part A: until 24 weeks and Part B: until 28 weeks
|
Time to Complete Remission (CR)
Time Frame: Part A: until 24 weeks and Part B: until 28 weeks
|
CR was defined as complete healing of all lesions and the absence of new lesions.
|
Part A: until 24 weeks and Part B: until 28 weeks
|
Time to Relapse After PRN1008 Treatment Discontinuation
Time Frame: Part A: until 24 weeks and Part B: until 28 weeks
|
Relapse was defined as appearance of ≥3 new lesions/month that do not heal spontaneously within 1 week, or by extension of established lesions, in a patient who has achieved disease control.
The median time to relapse was based on Kaplan-Meier estimate which considered censoring at end of follow-up for patients who didn't have an event.
A +/-3 days window for visits at Week 3 and 5, and +/-7 days window for visits at Week 9, 13, 17, 21, 25.
|
Part A: until 24 weeks and Part B: until 28 weeks
|
Cumulative Corticosteroid Usage
Time Frame: Part A: until 24 weeks and Part B: until 28 weeks
|
Cumulative corticosteroid usage
|
Part A: until 24 weeks and Part B: until 28 weeks
|
Percentage Change From Baseline in Pemphigus Disease Area Index (PDAI) Total Activity Scores
Time Frame: Part A: until 24 weeks and Part B: until 28 weeks
|
The PDAI questionnaire has 2 components including activity and damage.
The activity component consists of skin, scalp and mucosa parts, and the damage component consists of skin and scalp parts.
The total activity score was used for the summary of PDAI scores.
PDAI total activity score = Total skin activity + Total scalp activity + Total mucosa activity.
PDAI Total Activity Score ranged from 0 to 250 points representing disease activity (higher scores mean a worse outcome).
Negative change in total activity score from baseline indicates improvement in pemphigus activity.
|
Part A: until 24 weeks and Part B: until 28 weeks
|
Change From Baseline in Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) Total Activity Score
Time Frame: Part A: until 24 weeks and Part B: until 28 weeks
|
ABSIS Total Activity Score ranged from 0 to 206 points representing disease activity (higher scores mean a worse outcome).
Negative change in total activity score from baseline indicates improvement in pemphigus activity.
|
Part A: until 24 weeks and Part B: until 28 weeks
|
Change From Baseline in Autoimmune Bullous Diseases Quality of Life (ABQOL)
Time Frame: Part A: until 24 weeks and Part B: until 28 weeks
|
ABQOL score ranged from 0 to 68 points representing disease activity (higher scores mean a worse outcome).
|
Part A: until 24 weeks and Part B: until 28 weeks
|
Change From Baseline in Treatment of Autoimmune Bullous Diseases Quality of Life (TABQOL) Scores
Time Frame: Part A: until 24 weeks and Part B: until 28 weeks
|
TABQOL score ranged from 0 to 68 points representing disease activity (higher scores mean a worse outcome).
|
Part A: until 24 weeks and Part B: until 28 weeks
|
Change From Baseline in Appetite (SNAQ Score)
Time Frame: Part A: until 24 weeks and Part B: until 28 weeks
|
Simplified Nutritional Appetite Questionnaire (SNAQ) score ranged from 0 to 20 points representing disease activity (higher scores mean a better outcome).
|
Part A: until 24 weeks and Part B: until 28 weeks
|
Collaborators and Investigators
Collaborators
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PRN1008-005
- 2015-003564-37 (EUDRACT_NUMBER)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Pemphigus Vulgaris
-
Cabaletta BioRecruitingMucosal -Dominant Pemphigus VulgarisUnited States
-
Cairo UniversityCompletedOral Pemphigus VulgarisEgypt
-
Hoffmann-La RocheAspreva PharmaceuticalsCompletedPemphigus Vulgaris (PV)Turkey, Switzerland, United States, Germany, United Kingdom, Ukraine, Israel, Canada
-
argenxCompletedPemphigus Vulgaris | Pemphigus FoliaceusUnited States, Australia, Bulgaria, China, France, Georgia, Germany, Greece, Hungary, India, Israel, Italy, Japan, Poland, Romania, Russian Federation, Serbia, Spain, Turkey, Ukraine, United Kingdom
-
National Institute of Allergy and Infectious Diseases...Rho Federal Systems Division, Inc.; Autoimmunity Centers of ExcellenceTerminatedPemphigus Vulgaris | Pemphigus FoliaceusUnited States
-
argenxCompletedPemphigus Vulgaris | Pemphigus FoliaceusGermany, Hungary, Israel, Italy, Ukraine
-
argenxActive, not recruitingPemphigus Vulgaris | Pemphigus FoliaceusUnited States, Germany, Italy, Australia, Bulgaria, China, France, Georgia, Greece, Hungary, India, Israel, Japan, Poland, Romania, Russian Federation, Serbia, Spain, Turkey, Ukraine, United Kingdom
-
Assistance Publique - Hôpitaux de ParisInstitut National de la Santé Et de la Recherche Médicale, FranceUnknownPemphigus Vulgaris | Pemphigus FoliaceusFrance
-
Alexion PharmaceuticalsTerminatedPemphigus | Pemphigus Vulgaris | Pemphigus FoliaceusUnited States
-
Kemia, IncCompleted
Clinical Trials on PRN1008
-
SanofiCompletedAtopic DermatitisNetherlands, Chile, United States, Canada, Czechia, Germany, Poland
-
Principia Biopharma, a Sanofi CompanyActive, not recruitingImmune Thrombocytopenia | Immune Thrombocytopenic PurpuraUnited States, Australia, Bulgaria, Canada, Czechia, Netherlands, Norway, United Kingdom
-
Principia Biopharma, a Sanofi CompanyRecruitingImmune ThrombocytopeniaUnited States, China, Argentina, Australia, Brazil, Canada, France, Hungary, Israel, Korea, Republic of, Mexico, Russian Federation, Singapore, Spain, Thailand, United Kingdom, Austria, Chile, Germany, Italy, Japan, Netherlands, Norway and more
-
SanofiActive, not recruitingWarm Autoimmune Hemolytic Anemia (wAIHA)United States, Austria, China, Denmark, Germany, Hungary, Italy, Spain, United Kingdom
-
SanofiCompletedAsthmaSpain, Korea, Republic of, Chile, Mexico, United Kingdom, Argentina, Bulgaria, Canada, Hungary, Poland, Romania, Turkey, Germany
-
SanofiActive, not recruitingChronic Spontaneous UrticariaChile, Taiwan, Argentina, Germany, Canada, Russian Federation, Netherlands, Korea, Republic of, Spain, Greece, Italy, Japan, Poland
-
Principia Biopharma, a Sanofi CompanyMassachusetts General HospitalActive, not recruitingImmunoglobulin G4 Related DiseaseUnited States, Canada, France, Italy, Spain