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A Study of PRN1008 in Adult Patients With Pemphigus Vulgaris

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02704429
Recruitment Status : Active, not recruiting
First Posted : March 10, 2016
Last Update Posted : January 13, 2020
Sponsor:
Collaborator:
Principia Biopharma Australia Pty Ltd.
Information provided by (Responsible Party):
Principia Biopharma Inc.

Tracking Information
First Submitted Date  ICMJE February 24, 2016
First Posted Date  ICMJE March 10, 2016
Last Update Posted Date January 13, 2020
Study Start Date  ICMJE February 2016
Actual Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 29, 2018)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 4, 2016)
  • Incidence of treatment-emergent adverse events at 12 weeks [ Time Frame: 12 weeks treatment ]
    The incidence of treatment-emergent adverse events (TEAEs), including clinically significant changes in physical examination, laboratory tests, and vital signs.
  • 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.
Change History Complete list of historical versions of study NCT02704429 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 29, 2018)
  • 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
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: March 4, 2016)
  • Time to control of disease activity (CDA) [ Time Frame: 12 week treatment; 12 week follow up ]
    Time to control of disease activity (CDA) as defined in European Academy of Dermatology and Venereology (EADV) 2015 Pemphigus S2 Guideline
  • Time to end of consolidation phase [ Time Frame: 12 week treatment; 12 week follow up ]
    Time to end of consolidation phase as defined in European Academy of Dermatology and Venereology (EADV) 2015 Pemphigus S2 Guideline
  • Time to complete remission [ Time Frame: 12 week treatment; 12 week follow up ]
    Time to complete remission as defined in European Academy of Dermatology2015 Pemphigus S2 Guideline
  • Time to relapse after PRN1008 treatment discontinuation [ Time Frame: 12 week treatment; 12 week follow up ]
    Time to relapse after PRN1008 treatment discontinuation as defined in European Academy of Dermatology and Venereology (EADV) 2015 Pemphigus S2 Guideline
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of PRN1008 in Adult Patients With Pemphigus Vulgaris
Official Title  ICMJE 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
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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE Pemphigus Vulgaris
Intervention  ICMJE Drug: PRN1008
Part A: PRN1008, oral dose, 12 weeks; Part B: PRN1008, oral dose 24 weeks
Other Name: BTK inhibitor
Study Arms  ICMJE Experimental: PRN1008
Part A: Open-label PRN1008, 12 weeks; 12 week follow up; Part B: Open-label PRN1008, 24 weeks;4 weeks follow up
Intervention: Drug: PRN1008
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 11, 2019)
42
Original Estimated Enrollment  ICMJE
 (submitted: March 4, 2016)
25
Estimated Study Completion Date  ICMJE January 2020
Actual Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Croatia,   France,   Greece,   Israel
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02704429
Other Study ID Numbers  ICMJE PRN1008-005
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Principia Biopharma Inc.
Study Sponsor  ICMJE Principia Biopharma Inc.
Collaborators  ICMJE Principia Biopharma Australia Pty Ltd.
Investigators  ICMJE
Study Director: Dolca Thomas, MD Principia Biopharma
PRS Account Principia Biopharma Inc.
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP