A Study of PRN1008 in Patients With Pemphigus

Principia Biopharma

Status and phase: Terminated; Phase 3

Conditions: Pemphigus

Treatments: Drug: Rilzabrutinib; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03762265

2018-002261-19 (EudraCT Number)

PRN1008-012 (Other Identifier)

EFC17092

Details and patient eligibility

About

This was a Phase 3 randomized, parallel-group, double-blind, placebo-controlled trial (blinded treatment [BT] period) followed by an open-label extension [OLE] period intended to evaluate the efficacy and safety of oral PRN1008 in moderate to severe pemphigus. After completing the open-label extension period, eligible participants might continue in a long term extension (LTE) Period of 48 weeks.

Full description

A total of 131 male or female participants with newly diagnosed or relapsing moderate to severe pemphigus (pemphigus vulgaris [PV] or pemphigus foliaceus [PF]) were enrolled in the trial worldwide.

The trial would last 68 weeks (approximately 17 months) for each participant. For participants eligible to enroll in the LTE, the trial might last up to 116 weeks.

Participants were randomized at Day 1, using a 1:1 ratio to receive PRN1008 or placebo twice per day, by relapsing/newly diagnosed disease history (newly diagnosed defined as within 6 months of screening).

Enrollment: 131 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female participants, 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.
• Positive circulating anti-desmoglein 1 (anti-dsg1) or 3 autoantibody titer.
• At screening, pemphigus disease area index score of at least 9 points for relapsing participants or at least 15 points for newly diagnosed participants.
• Adequate hematologic, hepatic, and renal function.
• Effective means of contraception.

Exclusion criteria

• Suspected paraneoplastic pemphigus and other forms of pemphigus that were not PV or PF.
• Previous use of a Bruton tyrosine kinase inhibitor.
• Pregnant or lactating women.
• Electrocardiogram clinically significant abnormalities.
• 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.
• Use of immunologic response modifiers as concomitant medication and with the washout period.
• Use of proton pump inhibitor drugs such as omeprazole and esomeprazole within 3 days of Day 1.
• Concomitant use of known strong-to-moderate inducers or inhibitors of cytochrome P450 3A (CYP3A) within 3 days or 5 half-lives (whichever is longer) of Day 1
• Use of CYP3A-sensitive substrate drugs.
• Had received any investigational drug within the 30 days before Day 1.
• History of drug abuse within the previous 12 months.
• Alcoholism or excessive alcohol use.
• Any other clinically significant disease, condition or medical history that, in the opinion of the Investigator, would interfere with participant safety, trial evaluations, and/or trial procedures.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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131 participants in 2 patient groups, including a placebo group

Placebo Then Rilzabrutinib

Placebo Comparator group

Description:

In BT period, participants received placebo orally twice daily (BID) up to 37 weeks along with sponsor-provided corticosteroids (CS). After at least two weeks of control of disease activity (CDA; no new lesions and established lesions begin to heal), based on protocol-specified clinical criteria, investigators could decrease the CS dose to a minimum of 5 milligrams (mg) prednisone/prednisolone per day from Week 29 to Week 37. Post completion of BT period, eligible participants received rilzabrutinib 400 mg BID up to Week 61 in OLE period and those who were eligible after OLE period completion, continued the same treatment until Week 109 in LTE period according to protocol-specified criteria.

Treatment:

Drug: Rilzabrutinib

Drug: Placebo

Rilzabrutinib Then Rilzabrutinib

Experimental group

Description:

In BT period, participants received rilzabrutinib 400 mg orally BID up to 37 weeks along with sponsor-provided CS. After at least two weeks of CDA (no new lesions and established lesions begin to heal), based on protocol-specified clinical criteria, investigators could decrease the CS dose to a minimum of 5 mg prednisone/prednisolone per day from Week 29 to Week 37. Post completion of BT period, eligible participants received rilzabrutinib 400 mg BID up to Week 61 in OLE period and those who were eligible after OLE period completion, continued the same treatment until Week 109 in LTE period according to protocol-specified criteria.

Treatment:

Drug: Rilzabrutinib