Clinical trial NCT04781816: Proof of Concept Study of SAR443122 in Patients With Cutaneous Lupus Erythematosus
Official title: Randomized, Double-blind, Placebo Controlled, Proof of Concept Study Assessing the Efficacy and Safety of the RIPK1-inhibitor SAR443122 in Patients With Moderate to Severe Subacute or Discoid/Chronic Cutaneous Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cutaneous Lupus Erythematosus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-03-04
Enrollment: 78
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: Primary Objective:

* Assess the efficacy of SAR443122 in cutaneous lupus erythematosus (CLE)

Secondary Objectives:

* Assess the effect of SAR443122 on the physician's global assessment of disease activity (PhysGA - disease activity)
* Assess the effect of SAR443122 on CLE induced itch and overall pain
* Assess the effect of SAR443122 on the proportion of disease activity responders compared to placebo
* Assess the effect of SAR443122 on the CLASI components score
* Assess the effect of SAR443122 on the Investigator's global assessment for CLE (IGA-CLE)
* Assess oral cavities for patients with oral lesions
* Assess the disease specific quality of life (QoL)
* Assess the safety and tolerability of SAR443122 in patients with CLE
* Assess the pharmacokinetics (PK) exposure of SAR443122 in patients with CLE

Detailed description: Total study duration per participant was up 20 weeks including:

* A screening period of up to 4 weeks
* A treatment period of 12 weeks
* A post treatment follow-up period of 4 weeks

Eligibility criteria: Inclusion criteria :

* Participants with cutaneous lupus erythematosus either in the form of discoid/chronic cutaneous lupus erythematosus or subacute cutaneous lupus erythematosus for at least 3 months before Screening.
* Participants with histologically confirmed and documented diagnosis within one year prior to Screening or during Screening period prior to randomization.
* Active cutaneous lupus erythematosus skin lesions and a Cutaneous Erythematosus.
* Disease Area and Severity Index activity (CLASI-A) ≥10 both at Screening and Baseline.
* Participant who was candidate for systemic treatment per Investigator's judgement.

Exclusion criteria:

* Systemic lupus erythematosus according to the 2012 SLICC criteria with major organ involvement.
* Suspected or proven drug induced lupus erythematosus, including patients with positive antihistone autoantibody tests.
* Autoimmune disease(s) other than systemic lupus erythematosus.
* Active skin diseases that may interfere with the study or study assessments.
* Exclusion related to tuberculosis, non-tuberculous mycobacterial infections, HIV, HBV, HCV, Herpes zoster, COVID-19 and other recurrent or recent serious infections.
* Prolonged QTcF ≥ 450 ms (by Fridericia formula) or clinically significant findings on electrocardiogram (ECG).
* Cannot avoid excessive UV exposure 4 weeks prior to baseline and during the study. Routine sun exposure through work are permitted but requires the use of sun block to sun exposed areas for at least 4 weeks prior to baseline and during the study.
* Concomitant treatment with topical immunosuppressants beyond a stable regimen of low to medium potency topical corticosteroids and/or topical calcineurin inhibitors during the study and two weeks before baseline visit.
* Initiation and/or changes in dosage of chloroquine/hydroxychloroquine within 12 weeks prior to Screening visit (or during Screening period) and/or the dose exceeding 2.3 mg/kg/day for chloroquine or 400 mg/day for hydroxychloroquine.
* Systemic treatments for cutaneous or systemic lupus erythematosus or immunosuppressive therapy for autoimmune disease other than the study medication.
* Systemic corticosteroids treatment \<4 weeks before baseline visit.
* Live vaccine(s) within 1 month prior to Screening, or plans to receive such vaccines during the study.
* Laboratory abnormalities at the Screening visit.

The above information was not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Percent Change From Baseline in Cutaneous Erythematosus Disease Area and Severity Index - Activity (CLASI-A) Sub-Score at Week 12
timeFrame: Baseline (Day 1) and Week 12
Secondary outcomes:
measure: Percentage of Participants With Physician's Global Assessment of Disease Activity (PhysGA- Disease Activity) of 0 or 1 (Disease Free or Almost Disease Free) at Week 12
timeFrame: Week 12
measure: Change From Baseline in Participants Reported Daily Worst Itch Using Peak Pruritus Numerical Rating Scale (Itch-NRS) at Week 12
timeFrame: Baseline (Day 1) and Week 12
measure: Change From Baseline in Participants Reported Daily Worst Pain Using Peak Pain Numerical Rating Scale (Pain-NRS) at Week 12
timeFrame: Baseline (Day 1) and Week 12
measure: Percentage of CLASI-A50 and CLASI-A75 Responders at Week 12
timeFrame: Week 12
measure: Change From Baseline in CLASI Components' Score Over Time
timeFrame: Baseline (Day 1) and Weeks 4, 8, 12, and 16
measure: Percentage of Participants With Investigator's Global Assessment of Cutaneous Lupus Erythematosus (IGA-CLE) Score of 0 or 1 (Clear Or Almost Clear) at Week 12
timeFrame: Week 12
measure: Change From Baseline to Week 12 in the Oral Health Impact Profile 14-Item Version (OHIP-14) for Participants With Oral Lesions at Baseline
timeFrame: Baseline (Day 1) and Week 12
measure: Change From Baseline in SKINDEX-29+3 Total Score at Week 12
timeFrame: Baseline (Day 1) and Week 12
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events of Special Interest (AESIs)
timeFrame: From first dose of study treatment (Day 1) up to end of study (Week 16)
measure: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Parameters
timeFrame: From first dose of study treatment (Day 1) up to end of study (Week 16)
measure: Number of Participants With PCSA in Clinical Chemistry
timeFrame: From first dose of study treatment (Day 1) up to end of study (Week 16)
measure: Number of Participants With PCSA in Urinalysis
timeFrame: From first dose of study treatment (Day 1) up to end of study (Week 16)
measure: Number of Participants With PCSA in Electrocardiogram (ECG)
timeFrame: From first dose of study treatment (Day 1) up to end of study (Week 16)
measure: Number of Participants With PCSA in Vital Signs
timeFrame: From first dose of study treatment (Day 1) up to end of study (Week 16)
measure: Maximum Plasma Concentration (Cmax) of SAR443122
timeFrame: 2-5 hours post first morning dose on Days 1, 57, and 85; 1 hour before morning dose on Days 57 and 85; 7-10 hours after morning dose on Day 57
measure: Time to Reach Maximum Plasma Concentration (Tmax) of SAR443122
timeFrame: 2-5 hours post first morning dose on Days 1, 57, and 85; 1 hour before morning dose on Days 57 and 85; 7-10 hours after morning dose on Day 57
measure: Area Under the Curve From Time 0 to 12 Hours (AUC0-12) of SAR443122
timeFrame: 2-5 hours post first morning dose on Days 1, 57, and 85; 1 hour before morning dose on Days 57 and 85; 7-10 hours after morning dose on Day 57
measure: Terminal Elimination Half-Life (t1/2z) of SAR443122
timeFrame: 1 hour before morning dose and 2-5 hours post first morning dose on Day 85
Other outcomes:
Locations:
city: Cooper City
country: United States
facility: GNP Research Site Number : 8400008
state: Florida
city: Charlotte
country: United States
facility: DJL Clinical Research, PLLC Site Number : 8400003
state: North Carolina
city: Columbus
country: United States
facility: ClinOhio Research Services Site Number : 8400007
state: Ohio
city: Houston
country: United States
facility: Prolato Clinical Research Center Site Number : 8400010
state: Texas
city: Caba
country: Argentina
facility: Investigational Site Number : 0320002
state: Buenos Aires
city: Caba
country: Argentina
facility: Investigational Site Number : 0320003
state: Buenos Aires
city: Caba
country: Argentina
facility: Investigational Site Number : 0320001
state: Buenos Aires
city: Rosario
country: Argentina
facility: Investigational Site Number : 0320004
state: Santa Fe
city: Mendoza
country: Argentina
facility: Investigational Site Number : 0320005
city: Camberwell
country: Australia
facility: Investigational Site Number : 0360001
state: Victoria
city: East Melbourne
country: Australia
facility: Investigational Site Number : 0360002
state: Victoria
city: London
country: Canada
facility: Investigational Site Number : 1240001
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number : 1240005
state: Ontario
city: Sherbrooke
country: Canada
facility: Investigational Site Number : 1240002
state: Quebec
city: Valdivia
country: Chile
facility: Investigational Site Number : 1520009
state: Los Ríos
city: Osorno
country: Chile
facility: Investigational Site Number : 1520006
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520007
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520003
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520001
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520002
state: Reg Metropolitana De Santiago
city: Brno
country: Czechia
facility: Investigational Site Number : 2030002
city: Nachod
country: Czechia
facility: Investigational Site Number : 2030004
city: Pardubice
country: Czechia
facility: Investigational Site Number : 2030006
city: Praha 6
country: Czechia
facility: Investigational Site Number : 2030005
city: Budapest
country: Hungary
facility: Investigational Site Number : 3480001
city: Szeged
country: Hungary
facility: Investigational Site Number : 3480002
city: Chandigarh
country: India
facility: Investigational Site Number : 3560002
city: Nagpur
country: India
facility: Investigational Site Number : 3560003
city: Nashik
country: India
facility: Investigational Site Number : 3560004
city: Genova
country: Italy
facility: Investigational Site Number : 3800001
city: Milano
country: Italy
facility: Investigational Site Number : 3800002
city: Benito Juarez
country: Mexico
facility: Investigational Site Number : 4840003
city: Chihuahua
country: Mexico
facility: Investigational Site Number : 4840004
city: Monterrey, Nuevo León
country: Mexico
facility: Investigational Site Number : 4840001
city: Veracruz
country: Mexico
facility: Investigational Site Number : 4840002
city: Lublin
country: Poland
facility: Investigational Site Number : 6160004
state: Lubelskie
city: Krakow
country: Poland
facility: Investigational Site Number : 6160006
state: Malopolskie
city: Katowice
country: Poland
facility: Investigational Site Number : 6160007
state: Slaskie
city: Krasnodar
country: Russian Federation
facility: Investigational Site Number : 6430004
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430005
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430002
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number : 6430001
city: Stavropol
country: Russian Federation
facility: Investigational Site Number : 6430003
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240002
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240007
state: Barcelona [Barcelona]
city: Hospitalet de Llobregat
country: Spain
facility: Investigational Site Number : 7240001
state: Barcelona [Barcelona]
city: Madrid
country: Spain
facility: Investigational Site Number : 7240004
state: Madrid, Comunidad De
city: Ivano-Frankivsk
country: Ukraine
facility: Investigational Site Number : 8040001
city: Kyiv
country: Ukraine
facility: Investigational Site Number : 8040002
city: London
country: United Kingdom
facility: Investigational Site Number : 8260003
state: London, City Of
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: