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Proof of Concept Study of SAR443122 in Patients With Cutaneous Lupus Erythematosus (CLEan)

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ClinicalTrials.gov Identifier: NCT04781816
Recruitment Status : Recruiting
First Posted : March 4, 2021
Last Update Posted : April 14, 2021
Sponsor:
Information provided by (Responsible Party):
Sanofi

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

Condition or disease Intervention/treatment Phase
Cutaneous Lupus Erythematosus Drug: SAR443122 Drug: Placebo Phase 2

Detailed 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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 88 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : April 1, 2021
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: SAR443122
SAR443122 for 12 weeks
Drug: SAR443122
Pharmaceutical form: Capsule Route of administration: Oral

Placebo Comparator: Placebo
Matching placebo
Drug: Placebo
Pharmaceutical form: Capsule Route of administration: Oral




Primary Outcome Measures :
  1. Percent change from baseline in Cutaneous Erythematosus Disease Area and Severity Index activity (CLASI-A) sub-score [ Time Frame: Baseline to Week 12 ]
    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.


Secondary Outcome Measures :
  1. Proportion of patients with physician's global assessment of disease activity (PhysGA - disease activity) of 0 or 1 (disease free or almost disease free) [ Time Frame: Week 12 ]
    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".

  2. Change from baseline in patients reported daily worst itch using Peak Pruritus Numerical Rating Scale (itch-NRS) [ Time Frame: Baseline to Week 12 ]
    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.

  3. Change from baseline in patients reported daily worst pain using Peak Pain Numerical Rating Scale (Pain-NRS) [ Time Frame: Baseline to Week 12 ]
    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.

  4. Proportion of CLASI-A50 and CLASI-A75 responders [ Time Frame: Week 12 ]
    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.

  5. Change from baseline in CLASI components' score [ Time Frame: Baseline up to Week 12 ]
    Change from baseline in CLASI components' score over time

  6. Proportion of patients with the Investigator's global assessment for CLE (IGA-CLE) score of 0 or 1 (clear or almost clear) [ Time Frame: Week 12 ]
    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).

  7. Change from baseline in Modified Oral Mucositis Index (MOMI) for patients with oral lesions at baseline [ Time Frame: Baseline to Week 12 ]
    MOMI is a semi quantitative scale designed to assess oral lesions based upon the severity of the lesions and the number of sites involved, including the intensity score for erythema, ranging from 0 to 3 and the score for ulcerations based on area of ulceration.

  8. Change from baseline in the Oral Health Impact Profile (OHIP-14) for patients with oral lesions at baseline [ Time Frame: Baseline to Week 12 ]
    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.

  9. Change from baseline in SKINDEX-29+3 total score [ Time Frame: Baseline to Week 12 ]
    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.

  10. Total number of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) [ Time Frame: Screening up to end of study (Week 16) ]
  11. Percent of TEAEs, SAEs and AESIs [ Time Frame: Screening up to end of study (Week 16) ]
  12. Percent of potentially clinically significant abnormalities (PCSAs) [ Time Frame: Screening up to end of study (Week 16) ]
    Percent of potentially clinically significant abnormalities (PCSAs) in laboratory tests, electrocardiogram (ECG) or vital signs through end of study

  13. SAR443122 plasma concentration [ Time Frame: Day 1, Day 57 and Day 85 ]
  14. Assessment of pharmacokinetic (PK) parameter: Cmax [ Time Frame: Day 1, Day 57 and Day 85 ]
    Maximum plasma concentration

  15. Assessment of PK parameter: tmax [ Time Frame: Day 1, Day 57 and Day 85 ]
    Time to reach Cmax

  16. Assessment of PK parameter: AUC0-tau [ Time Frame: Day 1, Day 57 and Day 85 ]
    Area under the plasma concentration - time curve over the dosing interval

  17. Assessment of PK parameter: t1/2z [ Time Frame: Day 1, Day 57 and Day 85 ]
    Elimination half-life



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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 Frederica formulation) 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04781816


Contacts
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Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext option 6 Contact-US@sanofi.com

Locations
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Australia
Investigational Site Number 0360001 Recruiting
Camberwell, Australia, 3124
Investigational Site Number 0360002 Recruiting
East Melbourne, Australia, 3002
Canada
Investigational Site Number 1240002 Recruiting
Sherbrooke, Canada, J1L 0H8
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT04781816    
Other Study ID Numbers: ACT16404
2020-004703-14 ( EudraCT Number )
U1111-1246-6784 ( Other Identifier: UTN )
First Posted: March 4, 2021    Key Record Dates
Last Update Posted: April 14, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Lupus Erythematosus, Systemic
Lupus Erythematosus, Cutaneous
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Skin Diseases