Clinical trial NCT02704429: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pemphigus Vulgaris
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2016-03-10
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Percentage of Participants With Treatment-emergent Adverse Events
timeFrame: Part A: until 24 weeks and Part B: until 28 weeks
measure: 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
timeFrame: 4 weeks
Secondary outcomes:
measure: Percentage of Participants Able to Achieve Control of Disease Activity (CDA) Without Corticosteroids Within 4 Weeks
timeFrame: 4 weeks
measure: Percentage of Participants Able to Achieve a Complete Response (CR) Without Corticosteroids
timeFrame: Part A: 12 weeks treatment and Part B: 24 weeks treatment
measure: Percentage of Participants Able to Achieve Complete Remission (CR) Without the Need for Doses of Prednisone or Prednisolone of Greater Than 0.5mg/kg
timeFrame: Part A: 12 weeks treatment and Part B: 24 weeks treatment
measure: Time to Control of Disease Activity (CDA)
timeFrame: Part A: until 24 weeks and Part B: until 28 weeks
measure: Time to End of Consolidation Phase (ECP)
timeFrame: Part A: until 24 weeks and Part B: until 28 weeks
measure: Time to Complete Remission (CR)
timeFrame: Part A: until 24 weeks and Part B: until 28 weeks
measure: Time to Relapse After PRN1008 Treatment Discontinuation
timeFrame: Part A: until 24 weeks and Part B: until 28 weeks
measure: Cumulative Corticosteroid Usage
timeFrame: Part A: until 24 weeks and Part B: until 28 weeks
measure: Percentage Change From Baseline in Pemphigus Disease Area Index (PDAI) Total Activity Scores
timeFrame: Part A: until 24 weeks and Part B: until 28 weeks
measure: Change From Baseline in Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) Total Activity Score
timeFrame: Part A: until 24 weeks and Part B: until 28 weeks
measure: Change From Baseline in Autoimmune Bullous Diseases Quality of Life (ABQOL)
timeFrame: Part A: until 24 weeks and Part B: until 28 weeks
measure: Change From Baseline in Treatment of Autoimmune Bullous Diseases Quality of Life (TABQOL) Scores
timeFrame: Part A: until 24 weeks and Part B: until 28 weeks
measure: Change From Baseline in Appetite (SNAQ Score)
timeFrame: Part A: until 24 weeks and Part B: until 28 weeks
Other outcomes:
Locations:
city: Kogarah
country: Australia
facility: Premier Specialists
state: New South Wales
city: East Melbourne
country: Australia
facility: Sinclair Dermatology
state: Victoria
city: Melbourne
country: Australia
facility: Royal Melbourne, Dermatology Office
state: Victoria
city: Osijek
country: Croatia
facility: Clinical Hospital Osijek
city: Zagreb
country: Croatia
facility: Klinichki Bolnicki Centar Zagreb
city: Bobigny
country: France
facility: Hôpital Avicenne
state: Siene-Saint Denis
city: Rouen
country: France
facility: Rouen University Hospital
city: Ioánnina
country: Greece
facility: University General Hospital of Ioannina
state: Ioannina
city: Larissa
country: Greece
facility: University Hospital of Larissa
state: Thessaly
city: Athens
country: Greece
facility: Hospital of Venereal and Skin Diseases A.Syggros
city: Thessaloniki
country: Greece
facility: Papageorgiou General Hospital of Thessaloniki
city: Ramat-Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: