A Study of PRN1008 in Adult Patients With Pemphigus Vulgaris
Condition: Pemphigus Vulgaris
MeSH terms: Pemphigus
Intervention: PRN1008
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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
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
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

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.
    

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