Clinical trial NCT03762265: A Study of PRN1008 in Patients With Pemphigus
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Pemphigus
Keywords: Pemphigus Vulgaris (PV)
Pemphigus Foliaceus (PF)
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2018-12-03
Enrollment: 131
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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).

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: From Week 29 to Week 37
measure: 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
timeFrame: From Week 29 to Week 37
Secondary outcomes:
measure: Cumulative Oral Corticosteroid Dose From Baseline to Week 37: PV mITT Population
timeFrame: Baseline to Week 37
measure: Cumulative Oral Corticosteroid Dose From Baseline to Week 37: mITT Population
timeFrame: Baseline to Week 37
measure: Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: PV mITT Population
timeFrame: Baseline to Week 37
measure: Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: mITT Population
timeFrame: Baseline to Week 37
measure: Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: PV mITT Population
timeFrame: Baseline to Week 37
measure: Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Week 37: mITT Population
timeFrame: Baseline to Week 37
measure: Percentage of Participants Who Achieved Complete Remission With a Corticosteroids Dose of <=5 mg/Day From Week 29 to Week 37: PV mITT Population
timeFrame: From Week 29 to Week 37
measure: Percentage of Participants Who Achieved Complete Remission With a Corticosteroids Dose of <=5 mg/Day From Week 29 to Week 37: mITT Population
timeFrame: From Week 29 to Week 37
measure: Percentage of Participants Who Had Pemphigus Disease Area Index (PDAI) Score <3 With a Corticosteroids Dose <=10 mg/Day From Week 29 to Week 37: PV mITT Population
timeFrame: From Week 29 to Week 37
measure: Percentage of Participants Who Had Pemphigus Disease Area Index Score <3 With a Corticosteroids Dose <=10 mg/Day From Week 29 to Week 37: mITT Population
timeFrame: From Week 29 to Week 37
measure: Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: PV mITT Population
timeFrame: Baseline to Week 61 and Baseline to Week 109
measure: Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109: mITT Population
timeFrame: Baseline to Weeks 61 and Baseline to Week 109
measure: Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Baseline to Weeks 61 and 109: PV mITT Population
timeFrame: Baseline to Week 61 and Baseline to Week 109
measure: Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Baseline to Weeks 61 and 109: mITT Population
timeFrame: Baseline to Week 61 and Baseline to Week 109
measure: Glucocorticoid Toxicity Index (GTI) - Cumulative Worsening Score (CWS) and Aggregate Improvement Score (AIS) at Week 37: PV mITT Population
timeFrame: At Week 37
measure: Glucocorticoid Toxicity Index - Cumulative Worsening Score and Aggregate Improvement Score at Week 37: mITT Population
timeFrame: At Week 37
measure: Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population
timeFrame: Baseline, Weeks 5, 13, 25, 37, 61, and 109
measure: Change From Baseline in Pemphigus Disease Area Index Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population
timeFrame: Baseline, Weeks 5, 13, 25, 37, 61, and 109
measure: Change From Baseline in Autoimmune Bullous Disease Quality of Life (ABQOL) Score at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population
timeFrame: Baseline, Weeks 5, 13, 25, 37, 61, and 109
measure: Change From Baseline in Autoimmune Bullous Disease Quality of Life Score at Weeks 5, 13, 25, 37, 61, and 109: mITT Population
timeFrame: Baseline, Weeks 5, 13, 25, 37, 61, and 109
measure: Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: PV mITT Population
timeFrame: At Weeks 5, 13, 25, 37, 61, and 109
measure: Percentage of Participants With Autoimmune Bullous Disease Quality of Life Score of Zero at Weeks 5, 13, 25, 37, 61, and 109: mITT Population
timeFrame: At Weeks 5, 13, 25, 37, 61, and 109
measure: Change From Baseline in the European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogue Scale (VAS) Scores at Weeks 5, 13, 25, 37, 61, and 109
timeFrame: Baseline, Weeks 5, 13, 25, 37, 61, and 109
measure: Change From Baseline in the European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels Score: Individual Dimension at Weeks 5, 13, 25, 37, 61, and 109
timeFrame: Baseline, Weeks 5, 13, 25, 37, 61, and 109
measure: Time to First Complete Remission With a Corticosteroids Dose <=10 mg/Day From Baseline to Weeks 61 and 109
timeFrame: Baseline to Week 61 and Baseline to Week 109
measure: Total Number of Disease Relapses/Flares From Initial Control of Disease Activity (CDA) to Week 37: PV mITT Population
timeFrame: From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
measure: Total Number of Disease Relapses/Flares From Initial Control of Disease Activity to Week 37: mITT Population
timeFrame: From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
measure: Time to Initial Relapse/Flare From Initial Control of Disease Activity to Week 37: PV mITT Population
timeFrame: From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
measure: Time to Initial Relapse/Flare From Initial Control of Disease Activity to Week 37: mITT Population
timeFrame: From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
measure: Percentage of Participants With 3 or More New Lesions Within 1 Month That do Not Heal Spontaneously Within 1 Week, or With Extension of Established Lesions at Week 37: PV mITT Population
timeFrame: At Week 37
measure: Percentage of Participants With 3 or More New Lesions Within 1 Month That do Not Heal Spontaneously Within 1 Week, or With Extension of Established Lesions at Week 37: mITT Population
timeFrame: At Week 37
measure: Percentage of Participants With at Least One Disease Relapse/Flare From Initial Control of Disease Activity to Week 37: PV mITT Population
timeFrame: From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
measure: Percentage of Participants With at Least One Disease Relapse/Flare From Initial Control of Disease Activity to Week 37: mITT Population
timeFrame: From initial CDA up to Week 37 (i.e., during any time from Baseline up to Week 37)
measure: Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Week 37 to Week 61: PV mITT Population
timeFrame: From Week 37 to Week 61
measure: Cumulative Duration of Complete Remission With a Corticosteroids Dose <=10 mg/Day From Week 37 to Week 61: mITT Population
timeFrame: From Week 37 to Week 61
measure: Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Week 37 to Week 61: PV mITT Population
timeFrame: From Week 37 to Week 61
measure: Cumulative Duration of Complete Remission With a Corticosteroids Dose = 0 mg/Day From Week 37 to Week 61: mITT Population
timeFrame: From Week 37 to Week 61
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: BT Period: From Day 1 of Week 1 to Week 37, OLE Period: from Week 37 to Week 61 and LTE Period: from Week 61 up to 4 weeks after the last dose at Week 109 (i.e., up to Week 113)
measure: Pharmacokinetics (PK): Plasma Concentration of Rilzabrutinib
timeFrame: Pre-dose and 2 hours post-dose on Day 1
measure: Pharmacodynamics (PD): Change From Baseline in Antibody Levels - Anti-desmoglein 1 (Anti-dsg 1) and Anti-desmoglein 3 (Anti-dsg 3) at Weeks 13, 25, 37, 49, 61, 73, 85, 97, and 109: PV mITT Population
timeFrame: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, and 109
measure: Pharmacodynamics: Change From Baseline in Antibody Levels - Anti-desmoglein 1 (Anti-dsg 1) and Anti-desmoglein 3 (Anti-dsg 3) at Weeks 13, 25, 37, 49, 61, 73, 85, 97 and 109: mITT Population
timeFrame: Baseline, Weeks 13, 25, 37, 49, 61, 73, 85, 97, and 109
Other outcomes:
Locations:
city: Boca Raton
country: United States
facility: Central Recruiting (Principia Biopharma)
state: Florida
city: Coral Gables
country: United States
facility: Central Recruiting (Principia Biopharma)
state: Florida
city: Atlanta
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facility: Central Recruiting (Principia Biopharma)
state: Georgia
city: Ann Arbor
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state: Michigan
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state: Michigan
city: Rochester
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state: Minnesota
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state: New Mexico
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state: New York
city: New York
country: United States
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state: New York
city: Chapel Hill
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state: North Carolina
city: Durham
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state: North Carolina
city: Cleveland
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state: Ohio
city: Austin
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state: Texas
city: Murray
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state: Utah
city: Buenos Aires
country: Argentina
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city: Buenos Aires
country: Argentina
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city: San Nicolás
country: Argentina
facility: Central Recruiting (Principia Biopharma)
city: Fremantle
country: Australia
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state: Western Australia
city: Melbourne
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city: Sydney
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city: Campinas
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city: Pleven
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country: Italy
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city: Catania
country: Italy
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city: Florence
country: Italy
facility: Central Recruiting (Principia Biopharma)
city: Milan
country: Italy
facility: Central Recruiting (Principia Biopharma)
city: Padova
country: Italy
facility: Central Recruiting (Principia Biopharma)
city: Parma
country: Italy
facility: Central Recruiting (Principia Biopharma)
city: Rome
country: Italy
facility: Central Recruiting (Principia Biopharma)
city: Torino
country: Italy
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city: Gdańsk
country: Poland
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city: Kraków
country: Poland
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city: Lublin
country: Poland
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city: Warsaw
country: Poland
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city: Wroclaw
country: Poland
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city: Wrocław
country: Poland
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city: Belgrade
country: Serbia
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city: Novi Sad
country: Serbia
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city: Barcelona
country: Spain
facility: Central Recruiting (Principia Biopharma)
city: Barcelona
country: Spain
facility: Central Recruiting (Principia Biopharma)
city: Barcelona
country: Spain
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city: Córdoba
country: Spain
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city: Madrid
country: Spain
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city: Pamplona
country: Spain
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city: Dalin
country: Taiwan
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city: Kaohsiung
country: Taiwan
facility: Central Recruiting (Principia Biopharma)
city: Taipei
country: Taiwan
facility: Central Recruiting (Principia Biopharma)
city: Fatih
country: Turkey
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city: Istanbul
country: Turkey
facility: Central Recruiting (Principia Biopharma)
city: Istanbul
country: Turkey
facility: Central Recruiting (Principia Biopharma)
city: Konyaaltı
country: Turkey
facility: Central Recruiting (Principia Biopharma)
city: Merkez
country: Turkey
facility: Central Recruiting (Principia Biopharma)
city: Dnipro
country: Ukraine
facility: Central Recruiting (Principia Biopharma)
city: Dnipro
country: Ukraine
facility: Central Recruiting (Principia Biopharma)
city: Kyiv
country: Ukraine
facility: Central Recruiting (Principia Biopharma)
city: Lviv
country: Ukraine
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city: Zaporizhzhya
country: Ukraine
facility: Central Recruiting (Principia Biopharma)
city: London
country: United Kingdom
facility: Central Recruiting (Principia Biopharma)
Study officials:
References: