Back to resultsA Study of PRN1008 in Adult Patients With Pemphigus Vulgaris
Primary Purpose
Pemphigus Vulgaris
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
PRN1008
Sponsored by
About this trial
This is an interventional treatment trial for Pemphigus Vulgaris
Eligibility Criteria
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 (≤ 10 mg/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
- Use of >10 mg per day of oral prednisolone per day within 2 weeks prior to Day 1 (inhaled and mucosal [for symptomatic treatment of oral lesions] corticosteroids are allowed)
- 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 there months or more of low body weight (BMI<17.5)
- 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
Sites / Locations
- Premier Specialists
- Sinclair Dermatology
- Royal Melbourne, Dermatology Office
- Clinical Hospital Osijek
- Klinichki Bolnicki Centar Zagreb
- Hôpital Avicenne
- Rouen University Hospital
- University General Hospital of Ioannina
- University Hospital of Larissa
- Hospital of Venereal and Skin Diseases A.Syggros
- Papageorgiou General Hospital of Thessaloniki
- Chaim Sheba Medical Center
- Tel Aviv Sourasky Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PRN1008
Arm Description
Part A: Open-label PRN1008, 12 weeks; 12 weeks follow-up; Part B: Open-label PRN1008, 24 weeks; 4 weeks follow-up
Outcomes
Primary Outcome Measures
Percentage of Participants With Treatment-emergent Adverse Events
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.
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
CDA was defined as the time at which new lesions cease to form and established lesions begin to heal.
Secondary Outcome Measures
Percentage of Participants Able to Achieve Control of Disease Activity (CDA) Without Corticosteroids Within 4 Weeks
CDA was defined as the time at which new lesions cease to form and established lesions begin to heal.
Percentage of Participants Able to Achieve a Complete Response (CR) Without Corticosteroids
CR was defined as complete healing of all lesions and the absence of new lesions.
Percentage of Participants Able to Achieve Complete Remission (CR) Without the Need for Doses of Prednisone or Prednisolone of Greater Than 0.5mg/kg
CR was defined as complete healing of all lesions and the absence of new lesions.
Time to Control of Disease Activity (CDA)
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.
Time to End of Consolidation Phase (ECP)
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.
Time to Complete Remission (CR)
CR was defined as complete healing of all lesions and the absence of new lesions.
Time to Relapse After PRN1008 Treatment Discontinuation
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.
Cumulative Corticosteroid Usage
Cumulative corticosteroid usage
Percentage Change From Baseline in Pemphigus Disease Area Index (PDAI) Total Activity Scores
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.
Change From Baseline in Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) Total Activity Score
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.
Change From Baseline in Autoimmune Bullous Diseases Quality of Life (ABQOL)
ABQOL score ranged from 0 to 68 points representing disease activity (higher scores mean a worse outcome).
Change From Baseline in Treatment of Autoimmune Bullous Diseases Quality of Life (TABQOL) Scores
TABQOL score ranged from 0 to 68 points representing disease activity (higher scores mean a worse outcome).
Change From Baseline in Appetite (SNAQ Score)
Simplified Nutritional Appetite Questionnaire (SNAQ) score ranged from 0 to 20 points representing disease activity (higher scores mean a better outcome).
Full Information
NCT ID
NCT02704429
First Posted
February 24, 2016
Last Updated
January 18, 2023
Sponsor
Principia Biopharma, a Sanofi Company
Collaborators
Principia Biopharma Australia Pty Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT02704429
Brief Title
A Study of PRN1008 in Adult Patients With Pemphigus Vulgaris
Official Title
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 Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
January 22, 2016 (Actual)
Primary Completion Date
December 18, 2019 (Actual)
Study Completion Date
January 10, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Principia Biopharma, a Sanofi Company
Collaborators
Principia Biopharma Australia Pty Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Open-label cohort study in adult patients with newly diagnosed or relapsing pemphigus vulgaris, with intra-patient dose-adjustment based on clinical response and BTK occupancy, and with conventional immunosuppressive "rescue treatment", if indicated. The duration of therapy in Part A will be 12 weeks, followed by 12 weeks of follow up. The extension phase, Part B includes 24 weeks of therapy, followed by 4 weeks of follow-up.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pemphigus Vulgaris
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Part A with 12 weeks treatment and 12 weeks follow-up. Part B with 24 weeks treatment and 4 weeks follow-up.
Masking
None (Open Label)
Masking Description
Open Label
Allocation
N/A
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PRN1008
Arm Type
Experimental
Arm Description
Part A: Open-label PRN1008, 12 weeks; 12 weeks follow-up; Part B: Open-label PRN1008, 24 weeks; 4 weeks follow-up
Intervention Type
Drug
Intervention Name(s)
PRN1008
Other Intervention Name(s)
BTK inhibitor, Rilzabrutinib
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Participants With Treatment-emergent Adverse Events
Description
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.
Time Frame
Part A: until 24 weeks and Part B: until 28 weeks
Title
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
Description
CDA was defined as the time at which new lesions cease to form and established lesions begin to heal.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants Able to Achieve Control of Disease Activity (CDA) Without Corticosteroids Within 4 Weeks
Description
CDA was defined as the time at which new lesions cease to form and established lesions begin to heal.
Time Frame
4 weeks
Title
Percentage of Participants Able to Achieve a Complete Response (CR) Without Corticosteroids
Description
CR was defined as complete healing of all lesions and the absence of new lesions.
Time Frame
Part A: 12 weeks treatment and Part B: 24 weeks treatment
Title
Percentage of Participants Able to Achieve Complete Remission (CR) Without the Need for Doses of Prednisone or Prednisolone of Greater Than 0.5mg/kg
Description
CR was defined as complete healing of all lesions and the absence of new lesions.
Time Frame
Part A: 12 weeks treatment and Part B: 24 weeks treatment
Title
Time to Control of Disease Activity (CDA)
Description
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.
Time Frame
Part A: until 24 weeks and Part B: until 28 weeks
Title
Time to End of Consolidation Phase (ECP)
Description
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.
Time Frame
Part A: until 24 weeks and Part B: until 28 weeks
Title
Time to Complete Remission (CR)
Description
CR was defined as complete healing of all lesions and the absence of new lesions.
Time Frame
Part A: until 24 weeks and Part B: until 28 weeks
Title
Time to Relapse After PRN1008 Treatment Discontinuation
Description
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.
Time Frame
Part A: until 24 weeks and Part B: until 28 weeks
Title
Cumulative Corticosteroid Usage
Description
Cumulative corticosteroid usage
Time Frame
Part A: until 24 weeks and Part B: until 28 weeks
Title
Percentage Change From Baseline in Pemphigus Disease Area Index (PDAI) Total Activity Scores
Description
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.
Time Frame
Part A: until 24 weeks and Part B: until 28 weeks
Title
Change From Baseline in Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) Total Activity Score
Description
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.
Time Frame
Part A: until 24 weeks and Part B: until 28 weeks
Title
Change From Baseline in Autoimmune Bullous Diseases Quality of Life (ABQOL)
Description
ABQOL score ranged from 0 to 68 points representing disease activity (higher scores mean a worse outcome).
Time Frame
Part A: until 24 weeks and Part B: until 28 weeks
Title
Change From Baseline in Treatment of Autoimmune Bullous Diseases Quality of Life (TABQOL) Scores
Description
TABQOL score ranged from 0 to 68 points representing disease activity (higher scores mean a worse outcome).
Time Frame
Part A: until 24 weeks and Part B: until 28 weeks
Title
Change From Baseline in Appetite (SNAQ Score)
Description
Simplified Nutritional Appetite Questionnaire (SNAQ) score ranged from 0 to 20 points representing disease activity (higher scores mean a better outcome).
Time Frame
Part A: until 24 weeks and Part B: until 28 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Premier Specialists
City
Kogarah
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
Facility Name
Sinclair Dermatology
City
East Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
Facility Name
Royal Melbourne, Dermatology Office
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
Clinical Hospital Osijek
City
Osijek
ZIP/Postal Code
31000
Country
Croatia
Facility Name
Klinichki Bolnicki Centar Zagreb
City
Zagreb
ZIP/Postal Code
10 000
Country
Croatia
Facility Name
Hôpital Avicenne
City
Bobigny
State/Province
Siene-Saint Denis
ZIP/Postal Code
93009
Country
France
Facility Name
Rouen University Hospital
City
Rouen
ZIP/Postal Code
76038
Country
France
Facility Name
University General Hospital of Ioannina
City
Ioánnina
State/Province
Ioannina
ZIP/Postal Code
45500
Country
Greece
Facility Name
University Hospital of Larissa
City
Larissa
State/Province
Thessaly
ZIP/Postal Code
41110
Country
Greece
Facility Name
Hospital of Venereal and Skin Diseases A.Syggros
City
Athens
ZIP/Postal Code
16121
Country
Greece
Facility Name
Papageorgiou General Hospital of Thessaloniki
City
Thessaloniki
ZIP/Postal Code
56429
Country
Greece
Facility Name
Chaim Sheba Medical Center
City
Ramat-Gan
ZIP/Postal Code
52621
Country
Israel
Facility Name
Tel Aviv Sourasky Medical Center
City
Tel Aviv
ZIP/Postal Code
64239
Country
Israel
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Learn more about this trial
A Study of PRN1008 in Adult Patients With Pemphigus Vulgaris
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