A study to test if increasing doses of the drug INCB050465 is safe and well tolerated in patients with Pemphigus Vulgaris

Phase 1

Conditions: Pemphigus vulgaris
MedDRA version: 20.0 Level: LLT Classification code 10052802 Term: Pemphigus vulgaris System Organ Class: 100000004858
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2018-002146-37-FR

Lead Sponsor: Incyte Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Not specified

Target Recruitment: 18

Inclusion Criteria

1.Men and women aged 18 to 80 years at the time of consent.

2.Clinically documented and confirmed diagnosis of pemphigus vulgaris:
a)Minimum of 6 months of pemphigus vulgaris diagnosis
b)Positive for anti-DSG1 or DSG-3
c)PDAI score of 8 to 45 points
d)Have active skin, scalp, or mucosal lesions

3.Participants who have disease progression after treatment with standard therapies that are known to confer clinical benefit, or who are intolerant to treatment. There is no limit to the number of prior treatment regimens.

4.Willingness to avoid pregnancy or fathering children based on the criteria below.
a)Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 90 days after the last dose of study drug and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the participants and their understanding confirmed.
b)Women of childbearing potential must have a negative serum pregnancy test at screening and before the first dose on Day 1 and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed.
c)Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR postmenopausal, defined as = 12 months of amenorrhea before screening, confirmed by FSH levels at screening) are eligible.

5.If required, willing to receive PJP prophylaxis during the study period.
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 9
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 9

Exclusion Criteria

1.Pregnant or breast-feeding female.

2.Participants with pemphigus vulgaris who are treatment-naive.

3.Use of the following medications within the following periods before baseline:
a) 2Weeks:
i)Potent systemic CYP3A4 inhibitors and inducers or fluconazole. Note: Topical agents with limited systemic availability are permitted. Recommend to consult with medical monitors.
ii)Topical treatment of pemphigus vulgaris lesions that may affect the disease assessment activities (eg, corticosteroids or tacrolimus/pimecrolimus).
b)4 weeks: Systemic immunosuppressive (eg, cyclophosphamide and methotrexate), etanercept, anakinra, prednisone > 0.5 mg/kg per day (or oral corticosteroid equivalent dose).
c)12 weeks or 5 half-lives (whichever is longer): infliximab, adalimumab, golimumab, abatacept, tocilizumab, certolizumab, secukinumab, IVIG, plasmapheresis, or any other biologic or experimental treatment.
d)12 months: Anti-CD20 monoclonal antibody, for example, rituximab and ofatumumab.

4.Evidence or history of clinically significant infection or medical condition including the following:
a)Any other active skin disease or condition (eg, bacterial, fungal, or viral infection) that may interfere with the course, severity, or assessments of pemphigus vulgaris.
b)Chronic or ongoing infectious disease requiring long-term systemic treatment, including but not limited to chronic renal infection or chronic pulmonary infection with bronchiectasis.
c)Active systemic viral infection or any active viral infection that, based on the investigator's clinical assessment, makes the participant an unsuitable candidate for the study.
d)Positive test result for TB from the QuantiFERON®-TB Gold test or T-SPOT.TB test at screening (or, if 2 indeterminate tests, then as evaluated by a purified protein derivative test with a result of < 5 mm of induration within 3 months of screening).
e)A history of active TB (treated or untreated) or history of untreated latent TB.
f)Positive serology test results for HIV, HBsAg, HBV core antibody, or HCV (HCV antibody with positive HCV-RNA) at screening.
g)Received live vaccine within 4 weeks before baseline or planning to receive live vaccine during the course of the study or within 4 weeks after EOT.
h)Prolonged QT interval corrected for heart rate using Fridericia's formula (QTcF), defined as > 470 milliseconds for male and > 480 milliseconds for females.
i)History of malignancy within 5 years before baseline, other than a successfully treated nonmetastatic neoplasms (eg, cutaneous squamous cell carcinoma, basal cell carcinoma, localized carcinoma in situ of the cervix, or melanoma in situ)
j)History of solid organ transplant.
k)Any serious illness or medical, physical, or psychiatric condition(s) that, in the opinion of the investigator, would pose a significant risk to the participant or interfere with the interpretation of safety, efficacy, or pharmacodynamic data.

5)Participants with laboratory values at screening, defined in Table 6 in Protocol

6)Known or suspected allergy to INCB050465 or any component of the study drug.

7)Known history of

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the safety and tolerability of INCB050465 in participants with pemphigus vulgaris. ;Secondary Objective: To determine the systemic exposure to INCB050465. ;Primary end point(s): Frequency, duration, and severity of AEs, clinical laboratory test results, vital signs results, ECGs, and physical examination findings.;Timepoint(s) of evaluation of this end point: Throughout the study

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Assessment of Cmax, tmax, Cmin, AUC0-t, and CL/F.;Timepoint(s) of evaluation of this end point: Day 1, week 2, week 6

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