NCT03762265|TerminatedPhase 3ResultsFDA Drug

Study Stopped

Sponsor decision based on lack of efficacy

A Study of PRN1008 in Patients With Pemphigus

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial to Evaluate the Efficacy and Safety of Oral BTK Inhibitor Rilzabrutinib (PRN1008) in Moderate to Severe Pemphigus

Principia Biopharma, a Sanofi Company ClinicalTrials.gov

Compare

3 other identifiers

EFC17092PRN1008-0122018-002261-19

Study Type

interventional

Target

131

Locations

19 countries

Sites

Timeline

RegisteredDec 2018

StartedJan 2019

CompletionDec 2021

Brief Summary

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.

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

131

participants targeted

Target at P25-P50 for phase_3

Timeline

Completed

Started Jan 2019

Typical duration for phase_3

Geographic Reach

19 countries

88 active sites

Status

terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

2.9 years study duration

First Submitted

Initial submission to the registry

November 29, 2018

Completed

4 days until next milestone

First Posted

Study publicly available on registry

December 3, 2018

Completed

1 month until next milestone

Study Start

First participant enrolled

January 8, 2019

Completed

2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 30, 2021

Completed

5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 17, 2021

Completed

9 months until next milestone

Results Posted

Study results publicly available

September 21, 2022

Completed

Last Updated

August 2, 2023

Status Verified

July 1, 2023

Enrollment Period

2.6 years

First QC Date

November 29, 2018

Results QC Date

July 13, 2022

Last Update Submit

July 21, 2023

Conditions

Pemphigus

Keywords

Pemphigus Vulgaris (PV)Pemphigus Foliaceus (PF)

Outcome Measures

Primary Outcomes (2)

Percentage of Participants Who Achieved Complete Remission (CR) With a Corticosteroids Dose of Less Than or Equal to (<=) 10 mg/Day From Week 29 to Week 37: Pemphigus Vulgaris Participants in Modified Intent-to-Treat (PV mITT) Population
Complete remission was defined as absence of new and established lesions and was intended to mean "no disease activity" for 2 consecutive weeks, with Pemphigus Disease Area Index (PDAI) activity score =0 and CS dose \<=10 mg. PDAI score weighted for number and size of lesions with score of 0 (absent) to 10 given for skin (12 body locations), scalp and mucous membrane showing disease activity (erosions/blisters or new erythema). PDAI total score ranged from 0 to 250 points representing disease activity (120 points for skin activity; 10 points for scalp activity; 120 points for mucosal activity). Higher score indicated more disease activity. In this outcome measure (OM), percentage of participants who achieved CR while on a daily corticosteroids dose of \<=10 mg/day were reported.
From Week 29 to Week 37
Percentage of Participants Who Achieved Complete Remission With a Corticosteroids Dose of <=10 mg/Day From Week 29 to Week 37: Modified Intent-to-Treat (mITT) Population
Complete remission was defined as absence of new and established lesions and was intended to mean "no disease activity" for 2 consecutive weeks, with PDAI activity score =0 and CS dose \<=10 mg. PDAI score weighted for number and size of lesions with score of 0 (absent) to 10 given for skin (12 body locations), scalp and mucous membrane showing disease activity (erosions/blisters or new erythema). PDAI total score ranged from 0 to 250 points representing disease activity (120 points for skin activity; 10 points for scalp activity; 120 points for mucosal activity). Higher score indicated more disease activity. In this OM, percentage of participants who achieved CR while on a daily corticosteroids dose of \<=10 mg/day were reported.
From Week 29 to Week 37

Secondary Outcomes (41)

Cumulative Oral Corticosteroid Dose From Baseline to Week 37: PV mITT Population
Baseline to Week 37
Cumulative Oral Corticosteroid Dose From Baseline to Week 37: mITT Population
Baseline to Week 37
Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: PV mITT Population
Baseline to Week 37
Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: mITT Population
Baseline to Week 37
Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: PV mITT Population
Baseline to Week 37
+36 more secondary outcomes

Study Arms (2)

Placebo Then Rilzabrutinib

PLACEBO COMPARATOR

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.

Drug: RilzabrutinibDrug: Placebo

Rilzabrutinib Then Rilzabrutinib

EXPERIMENTAL

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.

Drug: Rilzabrutinib

Interventions

RilzabrutinibDRUG

Pharmaceutical form: Tablet Route of administration: Oral

Placebo Then RilzabrutinibRilzabrutinib Then Rilzabrutinib

PlaceboDRUG

Pharmaceutical form: Tablet Route of administration: Oral

Placebo Then Rilzabrutinib

Eligibility Criteria

Age18 Years - 80 Years

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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.

You may not qualify if:

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.

Contact the study team to confirm eligibility.