Proof of Concept Study of SAR443122 in Patients With Cutaneous Lupus Erythematosus

Cutaneous Lupus Erythematosus Clinical Trial

— CLEan  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04781816
• Other study ID #: ACT16404
• Secondary ID: 2020-004703-14U1
• Status: Completed
• Phase: Phase 2
• Start date: April 1, 2021
• Est. completion date: June 26, 2023

Study information

• Verified date: June 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

Total study duration per participant will be 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: June 26, 2023
• Est. primary completion date: May 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 is 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 is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Cutaneous Lupus Erythematosus
• Lupus Erythematosus, Cutaneous
• Lupus Erythematosus, Systemic

Intervention

Drug:
• SAR443122
Pharmaceutical form: Capsule Route of administration: Oral
• Placebo
Pharmaceutical form: Capsule Route of administration: Oral

Locations

Country	Name	City	State
Argentina	Investigational Site Number :0320001	Caba	Buenos Aires
Argentina	Investigational Site Number :0320002	Caba	Buenos Aires
Argentina	Investigational Site Number :0320003	Caba	Buenos Aires
Argentina	Investigational Site Number :0320005	Mendoza
Argentina	Investigational Site Number :0320004	Rosario	Santa Fe
Australia	Investigational Site Number :0360001	Camberwell	Victoria
Australia	Investigational Site Number :0360002	East Melbourne	Victoria
Canada	Investigational Site Number :1240001	London	Ontario
Canada	Investigational Site Number :1240002	Sherbrooke	Quebec
Canada	Investigational Site Number :1240005	Toronto	Ontario
Chile	Investigational Site Number :1520006	Osorno	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520001	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520002	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520003	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520007	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520009	Valdivia	Los Ríos
Czechia	Investigational Site Number :2030002	Brno
Czechia	Investigational Site Number :2030004	Nachod
Czechia	Investigational Site Number :2030006	Pardubice
Czechia	Investigational Site Number :2030005	Praha 6
Hungary	Investigational Site Number :3480001	Budapest
Hungary	Investigational Site Number :3480002	Szeged
India	Investigational Site Number :3560002	India
India	Investigational Site Number :3560003	Nagpur
India	Investigational Site Number :3560004	Nashik
India	Investigational Site Number :3560001	Secunderabad
Italy	Investigational Site Number :3800001	Genova
Italy	Investigational Site Number :3800002	Milano
Mexico	Investigational Site Number :4840003	Benito Juarez
Mexico	Investigational Site Number :4840004	Chihuahua
Mexico	Investigational Site Number :4840001	Monterrey	Nuevo León
Mexico	Investigational Site Number :4840002	Veracruz
Poland	Investigational Site Number :6160002	Gdansk	Pomorskie
Poland	Investigational Site Number :6160007	Katowice	Slaskie
Poland	Investigational Site Number :6160006	Krakow	Malopolskie
Poland	Investigational Site Number :6160004	Lublin	Lubelskie
Russian Federation	Investigational Site Number :6430004	Krasnodar
Russian Federation	Investigational Site Number :6430002	Moscow
Russian Federation	Investigational Site Number :6430005	Moscow
Russian Federation	Investigational Site Number :6430001	St-Petersburg
Russian Federation	Investigational Site Number :6430003	Stavropol
Spain	Investigational Site Number :7240002	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number :7240006	Barcelona
Spain	Investigational Site Number :7240007	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number :7240001	Hospitalet de Llobregat	Catalunya [Cataluña]
Spain	Investigational Site Number :7240004	Madrid	Madrid, Comunidad De
Ukraine	Investigational Site Number :8040001	Ivano-Frankivsk
Ukraine	Investigational Site Number :8040002	Kyiv
United Kingdom	Investigational Site Number :8260002	London
United Kingdom	Investigational Site Number :8260003	London	London, City Of
United States	DJL Clinical Research, PLLC-Site Number:8400003	Charlotte	North Carolina
United States	ClinOhio Research Services-Site Number:8400007	Columbus	Ohio
United States	GNP Research-Site Number:8400008	Cooper City	Florida
United States	Prolato Clinical Research Center-Site Number:8400010	Houston	Texas
United States	Millennium Clinical Trials-Site Number:8400001	Thousand Oaks	California

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Chile,  Czechia,  Hungary,  India,  Italy,  Mexico,  Poland,  Russian Federation,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change from baseline in Cutaneous Erythematosus Disease Area and Severity Index activity (CLASI-A) sub-score	The Cutaneous Erythematosus Disease Area and Severity Index (CLASI) is a clinician rated scale composed of 56 items designed to assess the disease activity and damage in CLE in adults. The disease activity (CLASI-A) sub-score ranges from 0 to 70: 0-9 indicating mild disease, 10-20 indicating moderate disease, and 21-70 indicating severe disease.	Baseline to Week 12
Secondary	Proportion of patients with physician's global assessment of disease activity (PhysGA - disease activity) of 0 or 1 (disease free or almost disease free)	The PhysGA-disease activity is a 5 point-Lickert scale instrument designed to assess physician-reported disease activity ranging from "Not active at all" to "Extremely active".	Week 12
Secondary	Change from baseline in patients reported daily worst itch using Peak Pruritus Numerical Rating Scale (itch-NRS)	The itch-NRS is a single item patient-reported outcome (PRO) tool that patients will use to report the intensity of their pruritus (itch) during a daily recall period. Patients will be asked to rate their worst itch on a 0 ("No itch") to 10 ("Worst itch imaginable") NRS.	Baseline to Week 12
Secondary	Change from baseline in patients reported daily worst pain using Peak Pain Numerical Rating Scale (Pain-NRS)	The Pain-NRS is a single item PRO tool that patients will use to report the intensity of their CLE-related pain (skin, oral, genital) during a daily recall period. Patients will be asked to rate their worst pain on a 0 ("No pain") to 10 ("Worst pain imaginable") NRS.	Baseline to Week 12
Secondary	Proportion of CLASI-A50 and CLASI-A75 responders	The CLASI-A50/75 response is defined as a patient achieved a decrease by at least 50%/75% of CLASI-A sub-score from baseline.	Week 12
Secondary	Change from baseline in CLASI components' score	Change from baseline in CLASI components' score over time	Baseline up to Week 12
Secondary	Proportion of patients with the Investigator's global assessment for CLE (IGA-CLE) score of 0 or 1 (clear or almost clear)	The IGA-CLE is a clinician reported outcome that allows for clinicians to assess the overall disease activity of CLE using a 5-point scale from 0 (clear) to 4 (severe).	Week 12
Secondary	Change from baseline in the Oral Health Impact Profile (OHIP-14) for patients with oral lesions at baseline	OHIP-14 is a PRO questionnaire measures people's perception of dysfunction, discomfort and disability attributed to oral conditions in adults. It is composed of 14 items that assess seven different dimensions. The OHIP-14 scores can range from 0 to 56 and higher OHIP-14 scores indicate worse oral-health-related quality of life.	Baseline to Week 12
Secondary	Change from baseline in SKINDEX-29+3 total score	Skindex-29 is a PRO measure designed to assess the effects of skin disease on patients' health-related quality of life in adults. It contains 29 items, distributed across 3 domains. Individual items are scored from 0 to100 in 25-point increments with 100 representing maximal disability. The Skindex 29+3 includes a fourth subscale (3 questions) to assess lupus-specific issues.	Baseline to Week 12
Secondary	Total number of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and adverse events of special interest (AESIs)		Screening up to end of study (Week 16)
Secondary	Percent of TEAEs, SAEs and AESIs		Screening up to end of study (Week 16)
Secondary	Percent of potentially clinically significant abnormalities (PCSAs)	Percent of potentially clinically significant abnormalities (PCSAs) in laboratory tests, electrocardiogram (ECG) or vital signs through end of study	Screening up to end of study (Week 16)
Secondary	SAR443122 plasma concentration		Day 1, Day 57 and Day 85
Secondary	Assessment of pharmacokinetic (PK) parameter: Cmax	Maximum plasma concentration	Day 1, Day 57 and Day 85
Secondary	Assessment of PK parameter: tmax	Time to reach Cmax	Day 1, Day 57 and Day 85
Secondary	Assessment of PK parameter: AUC0-tau	Area under the plasma concentration - time curve over the dosing interval	Day 1, Day 57 and Day 85
Secondary	Assessment of PK parameter: t1/2z	Elimination half-life	Day 1, Day 57 and Day 85

External Links

•   ACT16404 Cutaneous Lupus Erythematosus website