A study to evaluate the efficacy and safety of PRN1008 in patients with pemphigus
- Conditions
- pemphigus vulgaris [PV] or pemphigus foliaceus [PF]MedDRA version: 20.0Level: LLTClassification code 10052802Term: Pemphigus vulgarisSystem Organ Class: 100000004858MedDRA version: 21.0Level: LLTClassification code 10057054Term: Pemphigus foliaceousSystem Organ Class: 100000004858Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]
- Registration Number
- EUCTR2018-002261-19-BG
- Lead Sponsor
- Principia Biopharma
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 120
1. Male or female patients, aged 18 to 80 years old with moderate to severe, newly diagnosed or relapsing PV or PF, with a clinical presentation and histopathology consistent with PV or PF.
2. Positive circulating anti-dsg1 or 3 autoantibody titer
3. At screening PDAI score of at least 9 points for relapsing patients (> 6 months since diagnosis) or at least 15 points for newly diagnosed patients (diagnosed = 6 months prior to Screening)
4. Adequate hematologic, hepatic, and renal function (absolute neutrophil count = 1.5 × 109/L, hemoglobin (Hgb) > 9 g/dL, platelet count = 100 × 109/L, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) = 1.5 × upper limit of normal (ULN), albumin = 3 g/dL, creatinine = 1.5 × ULN
5. Female patients who are of reproductive potential must agree for the duration of the study to use an effective means of contraception (e.g., hormonal contraception methods that inhibit ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal ligation, vasectomized partner or condoms). Unless surgically sterile, postmenopausal females should have menopause confirmed by follicle-stimulating hormone (FSH) testing. For females considered not to have reproductive potential: any woman of age =55 years with amenorrhea for > than 1 year, will be considered as having confirmed menopause and FSH or pregnancy testing will not be needed. Postmenopausal females <55 years of age (defined as amenorrhea >1 year) must have menopause confirmed by lelvated FSH levels at screening. Surgically sterile females do not require any further confirmation of menopause and will not be considered to have reproductive potential.
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 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
1. Suspected paraneoplastic pemphigus and other forms of pemphigus that are not pemphigus vulgaris or pemphigus foliaceus
2. Previous use of a Bruton’s tyrosine kinase (BTK) inhibitor
3. Pregnant or lactating women
4. Electrocardiogram (ECG) findings of QT corrected for heart rate (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
5. A history of malignancy of any type within 5 years before Day 1, other than surgically excised non-melanoma skin cancers or in situ cervical cancer
6. Use of immunologic response modifiers as concomitant medication and with the following washout periods:
A) stop at least 2 weeks prior to Screening: mycophenolate mofetil, azathioprine, methotrexate, cyclosporine, dapsone, intravenous immunoglobulin (IVIG), Kinaret (anakinra), Enbrel (etanercept) or any other immunosuppressant not mentioned in this exclusion criterion;
B) 12 weeks prior to Screening: Remicade (infliximab), Humira (adalimumab), Simponi (golimumab), Orencia (abatercept), Actemra (tocilizumab), Cimzia (certolizumab), Cosentyx (secukinumab), plasmapheresis;
C) 6 months prior to Screening (or shorter if there is documented B cell reconstitution for anti-CD20 drugs): antiCD20 drugs such as rituximab, ofatumumab, other long-acting biologics
7. Use of proton pump inhibitor drugs such as omeprazole and esomeprazole within 3 days of Day 1(It is acceptable to change patient to H2 receptor blocking drugs prior to Day 1.)
8. Concomitant use of known strong-to-moderate inducers or inhibitors of CYP3A within 3 days or 5 half-lives (whichever is longer) of Day 1 (Appendix 8)
9. Use of CYP3A-sensitive substrate drugs with a narrow therapeutic index within 3 days or 5 half-lives (whichever is longer) of Day 1 and for the remainder of the trial including, but not limited to alfentanil, astemizole, cisapride, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus (topical or oral), or terfenadine
10. Has received any investigational drug (or is currently using an investigational device) within the 30 days before Day 1, 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 PRN1008/placebo 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 at Screening for human immunodeficiency virus (HIV), hepatitis B (surface and core antibodies unrelated to vaccination, surface antigen), or hepatitis C (anti-HCV antibody confirmed with Hep C RNA)
17. Positive interferon-gamma release assay (IGRA) (e.g., T-spot TB test, QuantiFERON®-TB Gold or QuantiFERON®-TB Gold Plus (QFTPlus)) at Screening. Unless the patient has latent TB and all of the
following 3 conditions are true:
a. Chest X-ray does not show evidence suggestive of active tuberculosis (TB) disease
b. There are no clinical signs and symptoms of pulmonary and/or extrapulmonary TB disease
c. Documented receipt of one of the following prophylactic treatment regimens:
- oral daily
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method