A Pilot Study Investigating the Safety, Clinical Activity, Drug Levels, and Effects on PRN 1008 in Patients with Newly Diagnosed or Relapsing Pemphigus Vulgaris

Phase 1

• Conditions: MedDRA version: 18.1Level: LLTClassification code 10052802Term: Pemphigus vulgarisSystem Organ Class: 100000004858; Therapeutic area: Diseases [C] - Immune System Diseases [C20]; Pemphigus: Pemphigus Vulgaris

• Registration Number: EUCTR2015-003564-37-GR
• 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: 2016-01-13
• Last Update Posted: 30 March 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

1 Male or female patients, aged 18 to 80 years old, with biopsy-proven, mild-moderate PV (PDAI 15 to 45) 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), azathioprine, mycophenylate mofetil, sulfasalazine and dapsone, is judged clinically acceptable, provided cessation of azathioprine, mycophenylate mofetil, sulfasalazine, and dapsone within two to four weeks is anticipated
2. BMI >17.5 and <40 kg/m2
3. Adequate hematologic, hepatic, and renal function (absolute neutrophil count =1.5 X 10^9/L, Hgb > 9 g/dL, platelet count =100 X 10^9/L, AST/ALT = 1.5 x ULN, albumin =3 g/dL, creatinine = ULN
4. Female patients or female partners of a male patient who are of reproductive potential must agree for the duration of the study to use an effective means of contraception (e.g., diaphragm plus spermicide, condoms, or oral contraceptive). Unless surgically sterile, postmenopausal females should have menopause confirmed by FSH testing.
5. Male patients must agree to use a condom during sexual intercourse with female partners who are of reproductive potential for the duration of PRN1008 treatment and for 12 weeks thereafter (i.e. during the entire period of follow up)
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Previous use of a BTK inhibitor
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: 1 week: cyclophosphamide; 4 weeks: Kinaret (anakinra) and Enbrel (etanercept); 12 weeks: Remicade (infliximab), Humira (adalimumab), Simponi (golimumab), Orencia (abatercept), Actemra (tocilizumab), Cimzia (certolizumab), Cosentyx (secukinumab), IVIG, plasmapheresis; 6 months: Rituxan/MabThera (rituximab), ofatumumab, any other anti-CD20 antibody
6. Use of >10 mg per day of oral prednisolone for more than 1 week within 4 weeks prior to Day 1 (inhaled and mucosal [for symptomatic treatment of oral lesions] corticosteroids are allowed)
7. Use of proton pump inhibitor drugs such as omeprazole, 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 within 7 days or 5 half-lives (whichever is longer) of study drug dosing
9. Use of CYP3A-sensitive substrate drugs with a narrow therapeutic index within 7 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 14 standard drinks per week
13. Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate study drug absorption
14. Donation of a unit or more of blood or blood products within 4 weeks prior to Day 1
15. History of solid organ transplant
16. 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)
17. History of active or latent tuberculosis (TB) infection (subjects must also test negative using the QuantiFERON® test to be eligible for the study)
18. Any other clinically significant disease, condition, or medical history that, in the opinion of the Investigator, would interfere with subject safety, study evaluations, and/or study procedures

Study & Design

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