Download PDF

Clinical Trial Results:
A 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

Summary
EudraCT number	2020-004703-14
Trial protocol	HU PL IT
Global end of trial date	26 Jun 2023

Results information
Results version number	v1(current)
This version publication date	06 Jul 2024
First version publication date	06 Jul 2024
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

ACT16404

ISRCTN number

US NCT number

NCT04781816

WHO universal trial number (UTN)

U1111-1246-6784

Sponsor organisation name

Sanofi aventis recherche & développement

Sponsor organisation address

1 avenue Pierre Brossolette, Chilly-Mazarin, France, 91385

Public contact

Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com

Scientific contact

Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

21 Aug 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

26 Jun 2023

Was the trial ended prematurely?

Main objective of the trial

To assess the efficacy of SAR443122 in cutaneous lupus erythematosus (CLE).

Protection of trial subjects

Participants were fully informed of all pertinent aspects of clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the participant and considering the local culture. During the course of the trail, participants were provided with individual participant cards indicating the nature of the trial the participant is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.

Background therapy

Evidence for comparator

Actual start date of recruitment

01 Apr 2021

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 4

Country: Number of subjects enrolled

Australia: 1

Country: Number of subjects enrolled

Canada: 4

Country: Number of subjects enrolled

Chile: 13

Country: Number of subjects enrolled

Czechia: 6

Country: Number of subjects enrolled

Spain: 9

Country: Number of subjects enrolled

United Kingdom: 2

Country: Number of subjects enrolled

Hungary: 3

Country: Number of subjects enrolled

India: 5

Country: Number of subjects enrolled

Italy: 4

Country: Number of subjects enrolled

Mexico: 12

Country: Number of subjects enrolled

Poland: 2

Country: Number of subjects enrolled

Russian Federation: 7

Country: Number of subjects enrolled

Ukraine: 3

Country: Number of subjects enrolled

United States: 3

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

The study was conducted at 50 centers in 15 countries. A total of 132 participants were screened from 01 April 2021 to 01 March 2023, of which 54 were screen failures. Screen failures were mainly due to not meeting the eligibility criteria.

Screening details

A total of 78 participants were randomized in a ratio of 1:1 to either SAR443122 or placebo arm. The randomization was stratified by subtype of CLE (discoid lupus erythematosus [DLE] or subacute cutaneous lupus erythematosus [SCLE]), baseline use of hydroxychloroquine/chloroquine (HCQ/CQ) and by region.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants received placebo matched to SAR443122 orally twice a day (BID) for 12 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Placebo matched to SAR443122 was administered orally BID for 12 weeks.

SAR443122

Arm description

Participants received SAR443122 300 mg orally BID for 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Eclitasertib

Investigational medicinal product code

Other name

DNL758

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

SAR443122 300 mg was administered orally BID for 12 weeks.

Number of subjects in period 1	Placebo	SAR443122
Started	40	38
Completed	38	35
Not completed	2	3
Adverse event, non-fatal	-	1
Not Related to Coronavirus Disease 2019	1	1
Withdrawal by Subject	1	1

Baseline characteristics

Top of page

Reporting group title

Placebo

Reporting group description

Participants received placebo matched to SAR443122 orally twice a day (BID) for 12 weeks.

Reporting group title

SAR443122

Reporting group description

Participants received SAR443122 300 mg orally BID for 12 weeks.

Reporting group values	Placebo	SAR443122	Total
Number of subjects	40	38	78
Age categorical
Units: Subjects
Age Continuous
Units: years
arithmetic mean (standard deviation)	46.3 ( 9.8 )	45.6 ( 10.7 )	-
Sex: Female, Male
Units:
Female	29	33	62
Male	11	5	16
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	4	3	7
Asian	4	2	6
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	1	2	3
White	31	30	61
More than one race	0	1	1
Unknown or Not Reported	0	0	0

End points

Top of page

Reporting group title

Placebo

Reporting group description

Participants received placebo matched to SAR443122 orally twice a day (BID) for 12 weeks.

Reporting group title

SAR443122

Reporting group description

Participants received SAR443122 300 mg orally BID for 12 weeks.

Primary: Percent Change From Baseline in Cutaneous Erythematosus Disease Area and Severity Index – Activity (CLASI-A) Sub-Score at Week 12

Top of page

End point title

Percent Change From Baseline in Cutaneous Erythematosus Disease Area and Severity Index – Activity (CLASI-A) Sub-Score at Week 12

End point description

The CLASI is a clinician rated scale designed to assess the disease activity and damage in CLE in adults. It is composed of 56 items covering 2 dimensions: the disease activity (CLASI-A) and the disease damage (CLASI-D). CLASI-A disease activity covers the domains: erythema, scale/hypertrophy, recent hair loss/alopecia, and mucous membrane lesions. CLASI-A sub-score ranges for 0 to 70, where 0-9 indicates mild disease, 10-20 indicates moderate disease, and 21-70 indicates severe disease. Higher score indicates a more severe skin disease. Baseline was defined as the Day 1 assessment value. Efficacy population included all randomized participants exposed to the investigational medicinal product (IMP), with available Baseline assessment of the CLASI-A who actually received at least 1 complete dose of IMP and with at least 1 post IMP administration measurement. Only participants with data collected at Week 12 are reported.

End point type

Primary

End point timeframe

Baseline (Day 1) and Week 12

End point values	Placebo	SAR443122
Number of subjects analysed	35	35
Units: percent change
least squares mean (standard error)	-37.05 ( 5.31 )	-42.76 ( 5.42 )

SAR443122 Versus Placebo

Statistical analysis description

Analysis was performed using mixed model with repeated measurements (MMRM) including fixed effects for baseline CLASI-A, post-baseline visit, geographical region, disease subtype, baseline use of CQ/HCQ, intervention group, visit-by- intervention group interaction, and visit-by-baseline-CLASI-A interaction.

Comparison groups

Placebo v SAR443122

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Least Square Mean Difference

Point estimate

-5.7

Confidence interval

level

90%

sides

2-sided

lower limit

-18.26

upper limit

6.85

Variability estimate

Standard error of the mean

Dispersion value

7.53

Secondary: Change From Baseline in Participants Reported Daily Worst Itch Using Peak Pruritus Numerical Rating Scale (Itch-NRS) at Week 12

Top of page

End point title

Change From Baseline in Participants Reported Daily Worst Itch Using Peak Pruritus Numerical Rating Scale (Itch-NRS) at Week 12

End point description

Peak Pruritus NRS (itch-NRS) is single item patient reported outcomes (PRO) tool that participants used to report intensity of their pruritus (itch) during daily recall period. Participants were asked to rate their worst itch on 0 (no itch) to 10 (worst itch imaginable) NRS by answering following question: “On a scale of 0 to 10, with 0 being ‘no itch’ and 10 being ‘worst itch imaginable’, how would you rate your itch at the worst moment during previous 24 hours?”. Total score on scale ranges from 0 (no itch) to 10 (worst itch imaginable). Higher score indicates more severe skin disease. Baseline was defined as average of daily non-missing scores obtained during the week prior to Day 1. Efficacy population included all randomized participants exposed to the IMP, with available Baseline assessment of the CLASI-A who actually received at least 1 complete dose of IMP and with at least 1 post IMP administration measurement. Only participants with data collected at Week 12 are reported.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

End point values	Placebo	SAR443122
Number of subjects analysed	40	36
Units: score on a scale
least squares mean (standard error)	-0.62 ( 0.37 )	-2.16 ( 0.39 )

No statistical analyses for this end point

Secondary: 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

Top of page

End point title

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

End point description

The PhysGA- disease activity is a 5 point-Lickert scale instrument designed to assess physician-reported disease activity. The investigators were asked the following question “How active would you say your patient's cutaneous lupus erythematosus is currently?” The total score on scale ranges from 0 (not active at all) to 4 (extremely active). Higher score indicates a more severe skin disease. Efficacy population included all randomized participants exposed to the IMP, with available Baseline assessment of the CLASI-A who actually received at least 1 complete dose of IMP and with at least 1 post IMP administration measurement.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	SAR443122
Number of subjects analysed	40	38
Units: percentage of participants
number (not applicable)	32.5	44.74

No statistical analyses for this end point

Secondary: Percentage of CLASI-A50 and CLASI-A75 Responders at Week 12

Top of page

End point title

Percentage of CLASI-A50 and CLASI-A75 Responders at Week 12

End point description

The CLASI is a clinician rated scale designed to assess the disease activity and damage in CLE in adults. It is composed of 56 items covering 2 dimensions: the disease activity (CLASI-A) and the disease damage (CLASI-D). CLASI-A disease activity covers the domains: erythema, scale/hypertrophy, recent hair loss/alopecia, and mucous membrane lesions. CLASI-A sub-score ranges for 0 to 70, where 0-9 indicates mild disease, 10-20 indicates moderate disease, and 21-70 indicates severe disease. Higher score indicates a more severe skin disease. The CLASI-A50/75 responder was defined as a participant who achieved a decrease by at least 50%/75% of CLASI-A sub-score from baseline. Efficacy population included all randomized participants exposed to the IMP, with available Baseline assessment of the CLASI-A who actually received at least 1 complete dose of IMP and with at least 1 post IMP administration measurement.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	SAR443122
Number of subjects analysed	40	38
Units: percentage of responders
number (not applicable)
CLASI-A50	45	44.74
CLASI-A75	10	23.68

No statistical analyses for this end point

Secondary: Change From Baseline in CLASI Components' Score Over Time

Top of page

End point title

Change From Baseline in CLASI Components' Score Over Time

End point description

CLASI is clinician rated scale composed of 56 items covering disease activity(CLASI-A);disease damage(CLASI-D). CLASI-A disease activity covers erythema, scale/hypertrophy, recent hair loss/alopecia, mucous membrane lesions. Sub-score ranges 0-70 (0-9=mild disease,10-20=moderate disease,21-70=severe disease). CLASI-D disease damage covers dyspigmentation,scarring/atrophy/panniculitis,clinically judged scarring of scalp(including scarring alopecia). Scale ranges 0(absence of disease damage) to 56(severe disease damage) using parameters of dyspigmentation and scarring. For CLASI-A and CLASI-D, higher score=more severe skin disease. Baseline=Day 1 assessment value. Efficacy population=all randomized participants exposed to IMP, with available Baseline assessment of CLASI-A who actually received at least 1 complete dose of IMP and with at least 1 post IMP administration measurement. Only participants with data collected at Weeks 4, 8, 12, and 16 for each specified category are reported.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Weeks 4, 8, 12, and 16

End point values	Placebo	SAR443122
Number of subjects analysed	40	38
Units: score on a scale
arithmetic mean (standard deviation)
Erythema: Weeks 4 (n=40, 37)	-2.33 ( 3.24 )	-2.14 ( 3.02 )
Erythema: Weeks 8 (n=38, 36)	-3.37 ( 4.48 )	-3.42 ( 3.80 )
Erythema: Weeks 12 (n=35, 35)	-4.97 ( 4.89 )	-4.17 ( 4.15 )
Erythema: Weeks 16 (n=34, 33)	-5.09 ( 4.00 )	-4.18 ( 4.38 )
Scale/Hypertrophy: Week 4 (n=40, 37)	-0.83 ( 1.32 )	-1.86 ( 2.47 )
Scale/Hypertrophy: Week 8 (n=38, 36)	-1.34 ( 2.34 )	-2.72 ( 3.19 )
Scale/Hypertrophy: Week 12 (n=35, 35)	-2.03 ( 2.99 )	-3.17 ( 3.34 )
Scale/Hypertrophy: Week 16 (n=34, 33)	-2.12 ( 2.58 )	-3.30 ( 3.54 )
Scarring/Atrophy/Panniculitis: Week 4 (n=40, 37)	-0.13 ( 0.88 )	-0.16 ( 0.83 )
Scarring/Atrophy/Panniculitis: Week 8 (n=38, 36)	-0.08 ( 1.08 )	-0.25 ( 0.87 )
Scarring/Atrophy/Panniculitis: Week 12 (n=35, 35)	-0.06 ( 1.37 )	-0.06 ( 1.26 )
Scarring/Atrophy/Panniculitis: Week 16 (n=34, 33)	-0.24 ( 1.48 )	-0.18 ( 1.26 )

No statistical analyses for this end point

Secondary: Change From Baseline in Participants Reported Daily Worst Pain Using Peak Pain Numerical Rating Scale (Pain-NRS) at Week 12

Top of page

End point title

Change From Baseline in Participants Reported Daily Worst Pain Using Peak Pain Numerical Rating Scale (Pain-NRS) at Week 12

End point description

Peak Pain NRS (Pain-NRS) is single item PRO tool that participants used to report intensity of their CLE-related pain (skin, oral, genital) during daily recall period. Participants were asked to rate their worst pain on 0 (no pain) to 10 (worst pain imaginable) NRS by answering following question: “On a scale of 0 to 10, with 0 being ‘no pain’ and 10 being ‘worst pain imaginable’, how would you rate your pain at worst moment due to your lupus during previous 24 hours?”. Total score on scale ranges from 0 (no pain) to 10 (worst pain imaginable). Higher score indicates more severe skin disease. Baseline was defined as average of daily non-missing scores obtained during week prior to Day 1. Efficacy population included all randomized participants exposed to IMP, with available Baseline assessment of the CLASI-A who actually received at least 1 complete dose of IMP and with at least 1 post IMP administration measurement. Only participants with data collected at Week 12 are reported.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

End point values	Placebo	SAR443122
Number of subjects analysed	40	36
Units: score on a scale
least squares mean (standard error)	-0.93 ( 0.32 )	-1.72 ( 0.34 )

No statistical analyses for this end point

Secondary: 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

Top of page

End point title

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

End point description

IGA-CLE is a clinician reported outcome (ClinRO) that allows for clinicians to assess overall disease activity of CLE using 5-point scale: 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe). Severity of CLE is determined by descriptions of combination of 3 plaque characteristics: erythema, scale, elevation. Erythema is primary characteristic that influenced the rating, with other characteristics considered secondarily. Telangiectatic change is not considered in rating. The assessment did not require presence of all 4 characteristics, severity was averaged over observed characteristics. Total score on scale ranges from 0 to 4. Higher score indicates a more severe skin disease. Efficacy population included all randomized participants exposed to IMP, with available Baseline assessment of the CLASI-A who actually received at least 1 complete dose of IMP and with at least 1 post IMP administration measurement. Only participants with data collected at Week 12 are reported.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	SAR443122
Number of subjects analysed	38	34
Units: percentage of participants
number (not applicable)	15.79	26.47

No statistical analyses for this end point

Secondary: Change From Baseline to Week 12 in the Oral Health Impact Profile 14-Item Version (OHIP-14) for Participants With Oral Lesions at Baseline

Top of page

End point title

Change From Baseline to Week 12 in the Oral Health Impact Profile 14-Item Version (OHIP-14) for Participants With Oral Lesions at Baseline

End point description

OHIP-14 is PRO questionnaire composed of 14 items that assess 7 dimensions. Each of 14 items has set of possible answers distributed in Likert scale(0 =never,1=hardly ever,2=occasionally,3=fairly often,4=very often)which represents frequency that individual perceives impact of oral health on 7 dimensions:functional limitation(2 items),physical pain(2 items),psychological discomfort(2 items),physical disability(2 items),psychological disability(2 items),social disability(2 items),handicap(2 items).OHIP-14 scores range 0-56 and calculated by summing the ordinal values for 14 items.Domain scores ranges 0-8.Higher OHIP-14 scores=worse oral-health-related quality of life. Baseline=Day 1 assessment value.Efficacy population=all randomized participants exposed to the IMP,with available Baseline assessment of the CLASI-A who actually received at least 1 complete dose of IMP and with at least 1 post IMP administration measurement.Only participants with data collected at Week 12 are reported.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

End point values	Placebo	SAR443122
Number of subjects analysed	10	13
Units: score on a scale
arithmetic mean (standard deviation)	-2.90 ( 7.68 )	-0.15 ( 4.79 )

No statistical analyses for this end point

Secondary: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events of Special Interest (AESIs)

Top of page

End point title

Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events of Special Interest (AESIs)

End point description

An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were defined as adverse events that occurred from the time of the first IMP administration up to the end of study visit. Serious adverse events (SAE): Any AE that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. An AESI: an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor’s product or program, for which ongoing monitoring and immediate notification by Investigator to Sponsor was required. Safety population included all randomized participants exposed to the IMP (regardless of the amount of treatment administered).

End point type

Secondary

End point timeframe

From first dose of study treatment (Day 1) up to end of study (Week 16)

End point values	Placebo	SAR443122
Number of subjects analysed	40	38
Units: participants
Any TEAE	18	22
Any TESAE	1	0
Any AESI	1	2

No statistical analyses for this end point

Secondary: Change From Baseline in SKINDEX-29+3 Total Score at Week 12

Top of page

End point title

Change From Baseline in SKINDEX-29+3 Total Score at Week 12

End point description

Skindex 29+3 is PRO measure designed to assess effects of skin disease on participants’ health-related quality of life in adults.It contains following domains:emotions(10 items),symptoms(7 items), functioning(12 items),lupus-specific issues(3 questions),and 1 item about treatment that is not part of the total score. Recall period is during the past week. Each item is rated on 5-point Likert scale (never, rarely, sometimes, often, all the time). These responses are then transformed to linear scale (0-100) in 25-point increments, where 100=maximal disability. Total score is average of participants' responses to items in given domain, ranging from 0-100, where higher scores indicate a greater impact on health-related quality of life. Baseline=Day 1 assessment value. Efficacy population=all randomized participants exposed to IMP, with available Baseline assessment of the CLASI-A who actually received at least 1 complete dose of IMP and with at least 1 post IMP administration measurement.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

End point values	Placebo	SAR443122
Number of subjects analysed	40	38
Units: score on a scale
least squares mean (standard error)	-9.09 ( 2.31 )	-11.09 ( 2.35 )

No statistical analyses for this end point

Secondary: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Parameters

Top of page

End point title

Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Parameters

End point description

PCSA values were defined as abnormal values considered medically important by the Sponsor, according to predefined criteria/thresholds based on literature reviews and defined by the Sponsor. Criteria for PCSA: Hemoglobin (Hb) ≤ 115 grams per liter (g/L) (Male [M]) or ≤ 95 g/L (Female [F]), ≥ 185 g/L (M) or ≥ 165 g/L (F), decrease from baseline ≥ 20 g/L; Platelets <100 x 10^9 per liter (/L) or ≥ 700 x 10^9/L; Erythrocytes ≥ 6 x 10^12/L; Leukocytes < 3 x 10^9/L (Non-Black [NB]); < 2 x 10^9/L (Black[B]); or ≥ 16 x 10^9/L; Neutrophils < 1.5 x 10^9/L (NB); < 1 x 10^9/L (B); Lymphocytes > 4 x 10^9/L; Monocytes > 0.7 x 10^9/L; Basophils > 0.1 x 10^9/L; Eosinophils > 0.5 x 10^9/L or > upper limit of normal range (ULN) (if ULN ≥ 0.5 x 10^9/L). Safety population included all randomized participants exposed to the IMP (regardless of the amount of treatment administered).

End point type

Secondary

End point timeframe

From first dose of study treatment (Day 1) up to end of study (Week 16)

End point values	Placebo	SAR443122
Number of subjects analysed	40	38
Units: participants
Hb: ≤ 115 g/L (M); ≤ 95 g/L (F)	0	1
Hb: ≥ 185 g/L (M); ≥ 165 g/L (F)	0	0
Decrease from baseline ≥ 20 g/L	0	0
Platelets < 100 x 10^9/L	0	0
Platelets ≥ 700 x 10^9/L	0	0
Erythrocytes ≥ 6 x 10^12/L	0	0
Leukocytes < 3 x 10^9/L (NB); < 2 x 10^9/L (B)	3	0
Leukocytes ≥ 16 x 10^9/L	0	0
Neutrophils < 1.5 x 10^9/L (NB); < 1 x 10^9/L (B)	3	0
Lymphocytes > 4 x 10^9/L	0	0
Monocytes > 0.7 x 10^9/L	1	3
Basophils > 0.1 x 10^9/L	6	5
Eosinophils > 0.5 x 10^9/L or > ULN	1	1

No statistical analyses for this end point

Secondary: Number of Participants With PCSA in Clinical Chemistry

Top of page

End point title

Number of Participants With PCSA in Clinical Chemistry

End point description

PCSA values were defined as abnormal values considered medically important by Sponsor, according to predefined criteria/thresholds based on literature reviews and defined by Sponsor. Criteria for PCSA:Glucose≤3.9 millimoles per liter(mmol/L) and <lower limit of normal range(LLN) or ≥11.1 mmol/L(unfasted);≥7 mmol/L(fasted);Creatine Kinase>3 ULN;Sodium≤129 mmol/L or ≥160 mmol/L; Potassium<3 mmol/L or ≥5.5 mmol/L;Creatinine≥150 micromoles per liter(μmol/L)(Adults) or ≥30% change from baseline or ≥100% change from baseline;Creatinine Clearance≥60-<90 milliliters per minute(mL/min)(mild decrease in glomerular filtration rate[GFR]) or ≥30-<60 mL/min(moderate decrease in GFR) or ≥15-<30 mL/min(severe decrease in GFR) or <15 mL/min(end stage renal disease);Alanine Aminotransferase>3ULN or >5ULN;Aspartate Aminotransferase>3ULN or>5ULN;Alkaline Phosphatase>1.5ULN;Total Bilirubin>1.5ULN.Safety population=all randomized participants exposed to IMP(regardless of amount of treatment administered).

End point type

Secondary

End point timeframe

From first dose of study treatment (Day 1) up to end of study (Week 16)

End point values	Placebo	SAR443122
Number of subjects analysed	40	38
Units: participants
Glucose ≤ 3.9 mmol/L and < LLN	4	1
Glucose ≥11.1 mmol/L(unfasted); ≥7mmol/L(fasted)	1	3
Creatine Kinase > 3 ULN	0	0
Sodium ≤ 129 mmol/L	0	0
Sodium ≥ 160 mmol/L	0	0
Potassium < 3 mmol/L	0	0
Potassium ≥ 5.5 mmol/L	2	0
Creatinine ≥ 150 μmol/L (Adults)	0	0
Creatinine ≥ 30% change from baseline	2	1
Creatinine ≥ 100% change from baseline	0	0
Creatinine Clearance ≥ 60 - < 90 mL/min	10	8
Creatinine Clearance ≥ 30 - < 60 mL/min	0	0
Creatinine Clearance ≥ 15 - < 30 mL/min	0	0
Creatinine Clearance < 15 mL/min	0	0
Alanine Aminotransferase > 3 ULN	1	2
Alanine Aminotransferase > 5 ULN	0	0
Aspartate Aminotransferase > 3 ULN	1	0
Aspartate Aminotransferase > 5 ULN	0	0
Alkaline Phosphatase > 1.5 ULN	5	0
Total Bilirubin > 1.5 ULN	0	0

No statistical analyses for this end point

Secondary: Number of Participants With PCSA in Electrocardiogram (ECG)

Top of page

End point title

Number of Participants With PCSA in Electrocardiogram (ECG)

End point description

PCSA values were defined as abnormal values considered medically important by the Sponsor, according to predefined criteria/thresholds based on literature reviews and defined by the Sponsor. Criteria for PCSA: Heart Rate (HR) < 50 beats/min (bpm) or < 50 bpm and decrease from baseline ≥ 20 bpm or < 40 bpm or > 90 bpm; PR Interval > 200 milliseconds (msec) or > 200 msec and increase from baseline ≥ 25% or > 220 msec; QRS Interval > 110 msec or 110 msec and increase from baseline ≥ 25% or > 120 msec; QT Interval > 500 msec; corrected QT (QTc) Interval > 450 msec or > 480 msec or increase from baseline [30-60] msec or increase from baseline > 60 msec. Safety population included all randomized participants exposed to the IMP (regardless of the amount of treatment administered). Only participants with data collected for each specified category at Week 16 are reported.

End point type

Secondary

End point timeframe

From first dose of study treatment (Day 1) up to end of study (Week 16)

End point values	Placebo	SAR443122
Number of subjects analysed	36	36
Units: participants
HR < 50 bpm	2	1
HR < 50 bpm and decrease from baseline ≥ 20 bpm	0	0
HR < 40 bpm	0	0
HR > 90 bpm	2	1
PR Interval > 200 msec	2	0
PR Interval >200 msec;increase from baseline ≥25%	0	0
PR Interval > 220 msec	0	0
QRS Interval > 110 msec	0	2
QRS Interval >110 msec;increase from baseline≥25%	0	0
QRS Interval > 120 msec	0	0
QT Interval > 500 msec	1	0
QTc Interval > 450 msec	1	1
QTc Interval > 480 msec	0	0
QTc Interval: Increase from baseline [30-60] msec	4	0
QTc Interval: Increase from baseline > 60 msec	0	0

No statistical analyses for this end point

Secondary: Number of Participants With PCSA in Urinalysis

Top of page

End point title

Number of Participants With PCSA in Urinalysis

End point description

PCSA values were defined as abnormal values considered medically important by the Sponsor, according to predefined criteria/thresholds based on literature reviews and defined by the Sponsor. Criteria for PCSA: pH ≤ 4.6 or ≥ 8. Safety population included all randomized participants exposed to the IMP (regardless of the amount of treatment administered). Only participants with data collected for each specified category at Week 16 are reported.

End point type

Secondary

End point timeframe

From first dose of study treatment (Day 1) up to end of study (Week 16)

End point values	Placebo	SAR443122
Number of subjects analysed	40	38
Units: participants
pH ≤ 4.6 (n=39, 38)	0	0
pH ≥ 8 (n=39, 38)	0	0

No statistical analyses for this end point

Secondary: Number of Participants With PCSA in Vital Signs

Top of page

End point title

Number of Participants With PCSA in Vital Signs

End point description

PCSA values were defined as abnormal values considered medically important by the Sponsor, according to predefined criteria/thresholds based on literature reviews and defined by the Sponsor. Criteria for PCSA: Diastolic Blood Pressure (DBP) ≤ 45 millimeters of mercury (mmHg) and decrease from baseline ≥ 10 mmHg or ≥ 110 mmHg and increase from baseline ≥ 10 mmHg; Pulse Rate (PR) ≤ 50 bpm and decrease from baseline ≥ 20 bpm or ≥ 120 bpm and increase from baseline ≥ 20 bpm; Systolic Blood Pressure (SBP) ≤ 95 mmHg and decrease from baseline ≥ 20 mmHg or ≥ 160 mmHg and increase from baseline ≥ 20 mmHg; Weight ≥ 5% decrease from baseline or ≥ 5% increase from baseline. Safety population included all randomized participants exposed to the IMP (regardless of the amount of treatment administered). Only participants with data collected for each specified category at Week 16 are reported.

End point type

Secondary

End point timeframe

From first dose of study treatment (Day 1) up to end of study (Week 16)

End point values	Placebo	SAR443122
Number of subjects analysed	40	38
Units: participants
DBP≤45 mmHg;decrease from baseline≥10mmHg(n=40,38)	0	1
DBP≥110mmHg;increase from baseline≥10mmHg(n=40,38)	0	0
PR≤50 bpm; decrease from baseline≥20 bpm(n=40,38)	0	0
PR≥120 bpm; increase from baseline≥20 bpm(n=40,38)	0	0
SBP≤95 mmHg;decrease from baseline≥20mmHg(n=40,38)	0	1
SBP≥160mmHg;increase from baseline≥20mmHg(n=40,38)	0	0
Weight ≥ 5% decrease from baseline (n=38,38)	3	5
Weight ≥ 5% increase from baseline (n=38,38)	1	2

No statistical analyses for this end point

Secondary: Maximum Plasma Concentration (Cmax) of SAR443122

Top of page

End point title

Maximum Plasma Concentration (Cmax) of SAR443122 ^[1]

End point description

Blood samples were collected at the specified timepoints. Cmax was assessed by a Bayesian analysis using the population PK model. PK population included all randomized and treated participants for whom the PK data are considered interpretable. Participants with data collected at Day 1, 57, and 85 are reported.

End point type

Secondary

End point 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

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only participants in the SAR443122 arm were analyzed in this endpoint.

End point values	SAR443122
Number of subjects analysed	36
Units: ng/mL
arithmetic mean (standard deviation)
Day 1 (n=36)	3334 ( 1365 )
Day 57 (n=33)	4875 ( 1541 )
Day 85 (n=31)	4896 ( 2013 )

No statistical analyses for this end point

Secondary: Time to Reach Maximum Plasma Concentration (tmax) of SAR443122

Top of page

End point title

Time to Reach Maximum Plasma Concentration (tmax) of SAR443122 ^[2]

End point description

Blood samples were collected at the specified timepoints. tmax was assessed by a Bayesian analysis using the population PK model. PK population included all randomized and treated participants for whom the PK data are considered interpretable. Participants with data collected at Day 1, 57, and 85 are reported. -9999 signifies that some tmax values were not calculable for participants with a low compliance, because all concentrations were below the lower limit of quantification.

End point type

Secondary

End point 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

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only participants in the SAR443122 arm were analyzed in this endpoint.

End point values	SAR443122
Number of subjects analysed	36
Units: hours
median (full range (min-max))
Day 1 (n=36)	2.80 (-9999 to 4.90)
Day 57 (n=33)	2.60 (-9999 to 4.35)
Day 85 (n=31)	2.55 (-9999 to 4.30)

No statistical analyses for this end point

Secondary: Area Under the Curve From Time 0 to 12 Hours (AUC0-12) of SAR443122

Top of page

End point title

Area Under the Curve From Time 0 to 12 Hours (AUC0-12) of SAR443122 ^[3]

End point description

Blood samples were collected at the specified timepoints. AUC0-12 was assessed by a Bayesian analysis using the population PK model. PK population included all randomized and treated participants for whom the PK data are considered interpretable. Participants with data collected at Day 1, 57, and 85 are reported.

End point type

Secondary

End point 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

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only participants in the SAR443122 arm were analyzed in this endpoint.

End point values	SAR443122
Number of subjects analysed	36
Units: nanogramhour per milliliter (ngh/mL)
arithmetic mean (standard deviation)
Day 1 (n=36)	30151 ( 14926 )
Day 57 (n=33)	40194 ( 15831 )
Day 85 (n=31)	44489 ( 19232 )

No statistical analyses for this end point

Secondary: Terminal Elimination Half-Life (t1/2z) of SAR443122

Top of page

End point title

Terminal Elimination Half-Life (t1/2z) of SAR443122 ^[4]

End point description

Blood samples were collected at the specified timepoints. t1/2z was assessed by a Bayesian analysis using the population PK model. PK population included all randomized and treated participants for whom the PK data are considered interpretable. Participants with data collected at Day 85 are reported.

End point type

Secondary

End point timeframe

1 hour before morning dose and 2-5 hours post first morning dose on Day 85

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only participants in the SAR443122 arm were analyzed in this endpoint.

End point values	SAR443122
Number of subjects analysed	36
Units: hours
arithmetic mean (standard deviation)	7.62 ( 2.28 )

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

From first dose of study treatment (Day 1) up to end of study (Week 16)

Adverse event reporting additional description

Analysis was performed on safety population.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

26.0

Reporting group title

Placebo

Reporting group description

Participants received placebo matched to SAR443122 orally BID for 12 weeks.

Reporting group title

SAR443122

Reporting group description

Participants received SAR443122 300 mg orally BID for 12 weeks.

Serious adverse events	Placebo	SAR443122
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Procedural Pain
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Placebo	SAR443122
Total subjects affected by non serious adverse events
subjects affected / exposed	18 / 40 (45.00%)	22 / 38 (57.89%)
General disorders and administration site conditions
Asthenia
subjects affected / exposed	2 / 40 (5.00%)	0 / 38 (0.00%)
occurrences all number	2	0
Fatigue
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Influenza Like Illness
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Peripheral Swelling
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Reproductive system and breast disorders
Breast Mass
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Dysmenorrhoea
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Oropharyngeal Pain
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Investigations
Alanine Aminotransferase Increased
subjects affected / exposed	1 / 40 (2.50%)	2 / 38 (5.26%)
occurrences all number	1	2
Aspartate Aminotransferase Increased
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Neutrophil Count Decreased
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Urine Protein/Creatinine Ratio Increased
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	2 / 40 (5.00%)	0 / 38 (0.00%)
occurrences all number	3	0
Procedural Pain
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Tooth Fracture
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Accidental Overdose
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Cardiac disorders
Coronary Artery Stenosis
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Nervous system disorders
Tension Headache
subjects affected / exposed	1 / 40 (2.50%)	1 / 38 (2.63%)
occurrences all number	1	1
Syncope
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Sciatica
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Headache
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Blood and lymphatic system disorders
Thrombocytopenia
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Neutropenia
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Eye disorders
Maculopathy
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Gastrointestinal disorders
Abdominal Pain Lower
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Constipation
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Odynophagia
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Nausea
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Haemorrhoids
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Diarrhoea
subjects affected / exposed	0 / 40 (0.00%)	2 / 38 (5.26%)
occurrences all number	0	2
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	0 / 40 (0.00%)	2 / 38 (5.26%)
occurrences all number	0	2
Onychoclasis
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Dry Skin
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Dermatitis Contact
subjects affected / exposed	1 / 40 (2.50%)	2 / 38 (5.26%)
occurrences all number	1	2
Dermatitis Allergic
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Cutaneous Lupus Erythematosus
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Alopecia
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	3 / 40 (7.50%)	2 / 38 (5.26%)
occurrences all number	3	2
Neck Pain
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Myalgia
subjects affected / exposed	2 / 40 (5.00%)	0 / 38 (0.00%)
occurrences all number	2	0
Muscular Weakness
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Bone Cyst
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Back Pain
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Infections and infestations
Bronchitis
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Covid-19
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Vulvovaginal Mycotic Infection
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Viral Upper Respiratory Tract Infection
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Urinary Tract Infection
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Upper Respiratory Tract Infection
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Tooth Abscess
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Tinea Pedis
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Periodontitis
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Folliculitis
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Gastroenteritis Viral
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Herpes Zoster
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Nail Infection
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Nasopharyngitis
subjects affected / exposed	1 / 40 (2.50%)	3 / 38 (7.89%)
occurrences all number	1	3
Oral Candidiasis
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Oral Herpes
subjects affected / exposed	0 / 40 (0.00%)	1 / 38 (2.63%)
occurrences all number	0	1
Metabolism and nutrition disorders
Obesity
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0
Hyperglycaemia
subjects affected / exposed	1 / 40 (2.50%)	0 / 38 (0.00%)
occurrences all number	1	0

More information

Top of page

Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A 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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percent Change From Baseline in Cutaneous Erythematosus Disease Area and Severity Index – Activity (CLASI-A) Sub-Score at Week 12

Primary: Percent Change From Baseline in Cutaneous Erythematosus Disease Area and Severity Index – Activity (CLASI-A) Sub-Score at Week 12

Secondary: Change From Baseline in Participants Reported Daily Worst Itch Using Peak Pruritus Numerical Rating Scale (Itch-NRS) at Week 12

Secondary: Change From Baseline in Participants Reported Daily Worst Itch Using Peak Pruritus Numerical Rating Scale (Itch-NRS) at Week 12

Secondary: 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

Secondary: 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

Secondary: Percentage of CLASI-A50 and CLASI-A75 Responders at Week 12

Secondary: Percentage of CLASI-A50 and CLASI-A75 Responders at Week 12

Secondary: Change From Baseline in CLASI Components' Score Over Time

Secondary: Change From Baseline in CLASI Components' Score Over Time

Secondary: Change From Baseline in Participants Reported Daily Worst Pain Using Peak Pain Numerical Rating Scale (Pain-NRS) at Week 12

Secondary: Change From Baseline in Participants Reported Daily Worst Pain Using Peak Pain Numerical Rating Scale (Pain-NRS) at Week 12

Secondary: 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

Secondary: 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

Secondary: Change From Baseline to Week 12 in the Oral Health Impact Profile 14-Item Version (OHIP-14) for Participants With Oral Lesions at Baseline

Secondary: Change From Baseline to Week 12 in the Oral Health Impact Profile 14-Item Version (OHIP-14) for Participants With Oral Lesions at Baseline

Secondary: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events of Special Interest (AESIs)

Secondary: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and Adverse Events of Special Interest (AESIs)

Secondary: Change From Baseline in SKINDEX-29+3 Total Score at Week 12

Secondary: Change From Baseline in SKINDEX-29+3 Total Score at Week 12

Secondary: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Parameters

Secondary: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Parameters

Secondary: Number of Participants With PCSA in Clinical Chemistry

Secondary: Number of Participants With PCSA in Clinical Chemistry

Secondary: Number of Participants With PCSA in Electrocardiogram (ECG)

Secondary: Number of Participants With PCSA in Electrocardiogram (ECG)

Secondary: Number of Participants With PCSA in Urinalysis

Secondary: Number of Participants With PCSA in Urinalysis

Secondary: Number of Participants With PCSA in Vital Signs

Secondary: Number of Participants With PCSA in Vital Signs

Secondary: Maximum Plasma Concentration (Cmax) of SAR443122

Secondary: Maximum Plasma Concentration (Cmax) of SAR443122

Secondary: Time to Reach Maximum Plasma Concentration (tmax) of SAR443122

Secondary: Time to Reach Maximum Plasma Concentration (tmax) of SAR443122

Secondary: Area Under the Curve From Time 0 to 12 Hours (AUC0-12) of SAR443122

Secondary: Area Under the Curve From Time 0 to 12 Hours (AUC0-12) of SAR443122

Secondary: Terminal Elimination Half-Life (t1/2z) of SAR443122

Secondary: Terminal Elimination Half-Life (t1/2z) of SAR443122

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A 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