A Study of PRN1008 in Adult Patients With Pemphigus Vulgaris

• ClinicalTrials.gov Identifier: NCT02704429
• Recruitment Status: Completed
• First Posted: March 10, 2016
• Last Update Posted: December 8, 2020
• Sponsor: Principia Biopharma, a Sanofi Company
• Collaborator: Principia Biopharma Australia Pty Ltd.
• Information provided by (Responsible Party): Principia Biopharma, a Sanofi Company

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.

Condition or disease	Intervention/treatment	Phase
Pemphigus Vulgaris	Drug: PRN1008	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 42 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention 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
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: January 22, 2016
• Actual Primary Completion Date: December 2019
• Actual Study Completion Date: January 10, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: PRN1008; Part A: Open-label PRN1008, 12 weeks; 12 week follow up; Part B: Open-label PRN1008, 24 weeks;4 weeks follow up	Drug: PRN1008; Part A: PRN1008, oral dose, 12 weeks; Part B: PRN1008, oral dose 24 weeks; Other Name: BTK inhibitor

Outcome Measures

Primary Outcome Measures :

1. Incidence of treatment-emergent adverse events [ Time Frame: Part A: 24 week treatment ]
   The incidence of treatment-emergent adverse events (TEAEs), including clinically significant changes in physical examination, laboratory tests, and vital signs.
2. Control of disease activity at 4 weeks [ Time Frame: 4 weeks treatment ]
   The proportion of subjects 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.

Secondary Outcome Measures :

1. Time to control of disease activity (CDA) [ Time Frame: Part A: 12 week treatment; 12 week follow up and Part B: 24 week treatment, 4 week follow-up ]
   Time to control of disease activity (CDA) defined in EADV 2015 Pemphigus S2 Guideline
2. Time to end of consolidation phase [ Time Frame: Part A: 12 week treatment; 12 week follow up and Part B: 24 week treatment, 4 week follow-up ]
   Time to end of consolidation phase as defined in EADV 2015 Pemphigus S2 Guideline
3. Time to complete response [ Time Frame: Part A: 12 week treatment; 12 week follow up and Part B: 24 week treatment, 4 week follow-up ]
   Time to complete response as defined in EADV 2015 Pemphigus S2 Guideline
4. Time to relapse after PRN1008 treatment discontinuation [ Time Frame: Part A: 12 week follow up and Part B: 4 week follow-up ]
   Time to relapse after PRN1008 treatment discontinuation
5. Cumulative corticosteroid usage [ Time Frame: Part A: 12 week treatment; 12 week follow up and Part B: 24 week treatment, 4 week follow-up ]
   Cumulative corticosteroid usage

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Australia, New South Wales

Premier Specialists

Kogarah, New South Wales, Australia, 2217

Australia, Victoria

Sinclair Dermatology

East Melbourne, Victoria, Australia, 3002

Royal Melbourne, Dermatology Office

Melbourne, Victoria, Australia, 3050

Croatia

Clinical Hospital Osijek

Osijek, Croatia, 31000

Klinichki Bolnicki Centar Zagreb

Zagreb, Croatia, 10 000

France

Hôpital Avicenne

Bobigny, Siene-Saint Denis, France, 93009

Rouen University Hospital

Rouen, France, 76038

Greece

University General Hospital of Ioannina

Ioánnina, Ioannina, Greece, 45500

University Hospital of Larissa

Larissa, Thessaly, Greece, 41110

Hospital of Venereal and Skin Diseases A.Syggros

Athens, Greece, 16121

Papageorgiou General Hospital of Thessaloniki

Thessaloniki, Greece, 56429

Israel

Chaim Sheba Medical Center

Ramat-Gan, Israel, 52621

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel, 64239

Sponsors and Collaborators

Principia Biopharma, a Sanofi Company

Principia Biopharma Australia Pty Ltd.

Investigators

• Study Director: Dolca Thomas, MD; Principia Biopharma

More Information

• Responsible Party: Principia Biopharma, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT02704429
• Other Study ID Numbers: PRN1008-005
• First Posted: March 10, 2016
• Last Update Posted: December 8, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Pemphigus; Skin Diseases, Vesiculobullous; Skin Diseases; Autoimmune Diseases; Immune System Diseases