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

Phase 1

• Conditions: Pemphigus: Pemphigus Vulgaris; MedDRA version: 20.0Level: LLTClassification code 10052802Term: Pemphigus vulgarisSystem Organ Class: 100000004858; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2015-003564-37-HR
• Lead Sponsor: Principia Biopharma Australia Pty Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-07-06
• Study Completion: 2020-01-10
• Last Update Posted: 21 December 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

1.Male or female patients, aged 18 to 80 years old, with biopsy proven (positive direct immunofluorescence and appearance on H&E microscopy), mild-moderate PV in Part A (PDAI 8 to 45) and mild-severe PV in Part B (PDAI 8 to 60)
2.Newly diagnosed or relapsing patients for whom an initial period of PRN1008 monotherapy or combination therapy with low-dose corticosteroids (=0.5 mg/kg of prednis[ol]one or equivalent), is judged clinically acceptable, provided tapering of the corticosteroid treatment regimen is anticipated with good clinical response to PRN1008
3.BMI > 17.5 and < 40 kg/m2 Part A only
4.Adequate hematologic, hepatic, and renal function (absolute neutrophil count = 1.5 X 109/L, Hgb > 9 g/dL, platelet count = 100 X 109/L, AST/ALT = 1.5 x ULN, albumin = 3 g/dL, creatinine = ULN (Part A) and creatinine = 1.5 x ULN (Part B)
5.Female patients who are of reproductive potential must agree for the duration of active treatment in the study to use an effective means of contraception (hormonal contraception methods that inhibits ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal ligation, vasectomized partner, condoms, or sexual abstinence). Unless surgically sterile, postmenopausal females should have menopause confirmed by FSH testing.
6.Able to provide written informed consent and agreeable to the schedule of assessments
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1.Previous use of a BTK inhibitor. Patients enrolled in a previous version of this protocol who are still in their 12-week active treatment period with PRN1008 are eligible to continue treatment, initially with their current dose level, under this amended protocol for an additional 12 weeks, i.e. 24 weeks total, following review and signature of the EC approved patient’s consent.Patients who completed Part A and did not discontinue the study due to a medical condition that might compromise safety assessments or for a PRN1008 related adverse event may be screened for entry under Part B.
2.Pregnant or lactating women
3.ECG findings of QTc > 450 msec (males) or > 470 msec (females), poorly controlled atrial fibrillation (i.e. symptomatic patients or a ventricular rate above 100 beats/min on ECG), or other clinically significant abnormalities
4.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
5.Use of immunologic response modifiers with the following periods prior to Day 1: as concomitant therapy, other immunologic response modifiers not detailed in this exclusion apart from corticosteroids; 1 week: cyclophosphamide; 4 weeks: IVIG, Kinaret (anakinra) and Enbrel (etanercept); 12 weeks: Remicade (infliximab), Humira (adalimumab), Simponi (golimumab), Orencia (abatercept), Actemra (tocilizumab), Cimzia (certolizumab), Cosentyx (secukinumab), plasmapheresis; 6 months: Rituxan/MabThera (rituximab), ofatumumab, any other anti-CD20 antibody, other long-acting biologics
6.More than 0.5 mg/kg of prednis(ol)one per day (low-dose corticosteroids”) within the two weeks prior to Day 1
7.Use of proton pump inhibitor drugs such as omeprazole and esomeprazole (it is acceptable to change patient to H2 receptor blocking drugs prior to the first dose of PRN1008)
8.Concomitant use of known strong-to-moderate inducers or inhibitors of CYP3A (Appendix 2) within 3 days or 5 half-lives (whichever is longer) of study drug dosing
9.Use of CYP3A-sensitive substrate drugs (Appendix 3) with a narrow therapeutic index within 3 days or 5 half-lives (whichever is longer) of study drug dosing including, but not limited to, alfentanil, astemizole, cisapride, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, or terfenadine
10.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)
11.History of drug abuse within the previous 12 months
12.Alcoholism or excessive alcohol use, defined as regular consumption of more than approximately 3 standard drinks per day
13.Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate study drug absorption
14.History of anorexia nervosa or periods of three months or more of low body weight (BMI < 17.5) in the past 5 years
15.Donation of a unit or more of blood or blood products within 4 weeks prior to Day 1
16.History of solid organ transplant
17.History of epilepsy or other forms of seizure in the last 5 years
18.Positive for screening for HIV, hepatitis B (surface and core antibodies unrelated to vaccination), or hepatitis C (anti-HCV antibody confirmed with Hep C RNA)
19.Positive interferon-gamma release ass

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified