A Study of PRN1008 in Adult Patients With Pemphigus Vulgaris

NCT02704429 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: PRN1008-0052015-003564-37
• Study Type: interventional
• Target: 42
• Locations: 5 countries
• Sites: 13

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.

Conditions

Pemphigus Vulgaris

Outcome Measures

Primary Outcomes (2)

• 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.

  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

  CDA was defined as the time at which new lesions cease to form and established lesions begin to heal.

  4 weeks

Secondary Outcomes (13)

• Percentage of Participants Able to Achieve Control of Disease Activity (CDA) Without Corticosteroids Within 4 Weeks

  4 weeks

• Percentage of Participants Able to Achieve a Complete Response (CR) Without Corticosteroids

  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

  Part A: 12 weeks treatment and Part B: 24 weeks treatment

• Time to Control of Disease Activity (CDA)

  Part A: until 24 weeks and Part B: until 28 weeks

• Time to End of Consolidation Phase (ECP)

  Part A: until 24 weeks and Part B: until 28 weeks

Study Arms (1)

PRN1008

EXPERIMENTAL

Part A: Open-label PRN1008, 12 weeks; 12 weeks follow-up; Part B: Open-label PRN1008, 24 weeks; 4 weeks follow-up

Drug: PRN1008

Interventions

PRN1008 DRUG

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.

Also known as: BTK inhibitor, Rilzabrutinib

PRN1008

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Principia Biopharma, a Sanofi Company: lead

Study Sites (13)

Premier Specialists

Kogarah, New South Wales, 2217, Australia

Location

Sinclair Dermatology

East Melbourne, Victoria, 3002, Australia

Location

Royal Melbourne, Dermatology Office

Melbourne, Victoria, 3050, Australia

Location

Clinical Hospital Osijek

Osijek, 31000, Croatia

Location

Klinichki Bolnicki Centar Zagreb

Zagreb, 10 000, Croatia

Location

Hôpital Avicenne

Bobigny, Siene-Saint Denis, 93009, France

Location

Rouen University Hospital

Rouen, 76038, France

Location

University General Hospital of Ioannina

Ioannina, Ioannina, 45500, Greece

Location

University Hospital of Larissa

Larissa, Thessaly, 41110, Greece

Location

Hospital of Venereal and Skin Diseases A.Syggros

Athens, 16121, Greece

Location

Papageorgiou General Hospital of Thessaloniki

Thessaloniki, 56429, Greece

Location

Chaim Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

MeSH Terms

Conditions

Pemphigus

Condition Hierarchy (Ancestors)

Skin Diseases, Vesiculobullous; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A with 12 weeks treatment and 12 weeks follow-up. Part B with 24 weeks treatment and 4 weeks follow-up.

Study Record Dates

• First Submitted: February 24, 2016
• First Posted: March 10, 2016
• Study Start: January 22, 2016
• Primary Completion: December 18, 2019
• Study Completion: January 10, 2020
• Last Updated: February 13, 2023
• Results First Posted: February 13, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will share

Locations

GR (4); IL (2); CR (2); AU (3); FR (2)