Efficacy and Safety of SAR441344 in the Treatment of Systemic Lupus Erythematosus (APATURA)

• ClinicalTrials.gov Identifier: NCT05039840
• Recruitment Status: Recruiting
• First Posted: September 10, 2021
• Last Update Posted: October 21, 2021
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Tracking Information

• First Submitted Date: September 1, 2021
• First Posted Date: September 10, 2021
• Last Update Posted Date: October 21, 2021
• Estimated Study Start Date: October 2021
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 1, 2021)

Percentage of participants who achieved a Systemic Lupus Erythematosus Responder Index (SRI-4) response at Week 24. [ Time Frame: At Week 24 ]

A composite endpoint, with SRI-4 response requiring a ≥ 4-point improvement (reduction) from baseline in Hybrid Safety of Estrogens in Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index (hSELENA-SLEDAI), no new British Isles Lupus Assessment Group (BILAG-2004) A organ domain scores, or ≥ 2 new BILAG-2004 B organ domain scores compared with baseline, no worsening from baseline in lupus disease activity, and no permanent discontinuation of study drug or use of new or increased medication for SLE other than defined per protocol.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 1, 2021)

• Percentage of participants who achieved an SRI-4 response in prespecified biomarker (BM) subgroups at Week 24 [ Time Frame: At Week 24 ]
• Percentage of participants who achieved a BILAG-based Composite Lupus Assessment (BICLA) response in prespecified BM subgroups at Week 24 [ Time Frame: At Week 24 ]
• Percentage of participants who achieved a BICLA response at Week 24 [ Time Frame: At Week 24 ]
• Percentage of participants whose prednisone dose was ≤ 7.5 mg at Week 16 and maintained through Week 24 in the subgroup with baseline prednisone ≥10 mg/day [ Time Frame: Until Week 24 ]
• Total cumulative corticosteroid dose over 24 weeks [ Time Frame: Until Week 24 ]
• Percentage of participants achieving an SRI-4 response at week 24 with sustained reduction of oral corticosteroids [ Time Frame: At Week 24 ]
• Percent change from baseline in percentage in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-A at Week 24 in the subgroup of participants with baseline CLASI-A score ≥8 [ Time Frame: At Week 24 ]
• Percentage of participants with ≥50% improvement in CLASI-A at Week 24 in the subgroup of participants with baseline CLASI-A score ≥8 [ Time Frame: At Week 24 ]
• Percentage of participants with ≥50% improvement in the number of tender and swollen joints at Week 24 (among participants with at least 4 joints affected at baseline) [ Time Frame: At Week 24 ]
• Incidence of treatment-emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs) from Baseline to Week 36 End of Study (EoS) [ Time Frame: Until Week 36 ]
• Incidence of study investigational medicinal product permanent discontinuations and study withdrawals due to TEAEs from Baseline to Week 36 (EoS) [ Time Frame: Until Week 36 ]
• Participants with medically significant changes in vital signs, electrocardiogram (ECG), and/or laboratory evaluation [ Time Frame: Until Week 36 ]
• Measurement of anti-drug antibodies (ADA) (before administration at Week 0, 4, 8, 12, 16, 20, 24 and after treatment discontinuation at Week 36) [ Time Frame: Until Week 36 ]
• SAR441344 concentrations over time [ Time Frame: Until Week 36 ]
• Pharmacokinetic parameters: maximum concentration (Cmax) [ Time Frame: Until Week 36 ]
• Pharmacokinetic parameters: time to Cmax (tmax) [ Time Frame: Until Week 36 ]
• Pharmacokinetic parameters: area under the curve over the dosing interval (AUC0-tau) [ Time Frame: Until Week 36 ]
• Pharmacokinetic parameters: terminal half-life (t1/2z). [ Time Frame: Until Week 36 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of SAR441344 in the Treatment of Systemic Lupus Erythematosus
• Official Title: Efficacy and Safety of SAR441344 in the Treatment of Systemic Lupus Erythematosus: A Randomized, Double Blind, Placebo-controlled, Phase 2, Proof of Concept Study

Brief Summary

This is a multinational, randomized, placebo-controlled, parallel treatment, Phase 2, double-blind, 2 arm study evaluating the efficacy and safety of SAR441344 in comparison with placebo in the treatment of participants aged 18 to 70 years with active Systemic Lupus Erythematosus (SLE). Study details include:

• Study duration: 36 weeks
• Treatment duration: 24 weeks
• Visit frequency: every 2 weeks

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Systemic Lupus Erythematosus

Intervention

• Drug: SAR441344 IV
  Pharmaceutical form: solution Route of administration: Intravenous infusion
• Drug: SAR441344 SC
  Pharmaceutical form: solution Route of administration: subcutaneous injection
• Drug: Placebo IV
  Pharmaceutical form: solution Route of administration: Intravenous infusion
• Drug: Placebo SC
  Pharmaceutical form: solution Route of administration: subcutaneous injection

Study Arms

• Experimental: SAR441344
  SAR441344 intravenous (IV) loading dose followed by subcutaneous (SC) doses, 24 weeks
  Interventions:

  • Drug: SAR441344 IV
  • Drug: SAR441344 SC
• Placebo Comparator: Placebo
  Placebo IV loading dose followed by SC, 24 weeks
  Interventions:

  • Drug: Placebo IV
  • Drug: Placebo SC

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 1, 2021): 116
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2023
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of SLE for at least 6 months prior to screening by fulfilling the Revised Criteria for Classification of SLE according to the 1997 Update of the 1982 ACR criteria
• Positive antinuclear antibody (ANA) (titer ≥1:80) during screening
• Positivity for at least one serological characteristic
• Total hSELENA-SLEDAI score ≥6 (including points attributed from arthritis and rash) during screening and at randomization as confirmed by a Sponsor-selected independent reviewer(s)
• At least 1 BILAG A score or 2 BILAG B scores during screening as confirmed by a Sponsor-selected independent reviewer(s)
• Receiving at least one of the standard of care (SOC) for SLE (combination is possible)
• Body weight within 45 kg to 120 kg (inclusive) at screening
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion Criteria:

• Primary diagnosis of a rheumatic disease besides SLE or an inflammatory joint or skin disease other than SLE that could confound the disease activity assessments
• Active and severe lupus nephritis
• Active severe or unstable neuropsychiatric SLE including but not limited to seizures, psychosis, acute confusional state, transverse myelitis, central nervous system vasculitis and optic neuritis
• Known or suspected drug-induced lupus
• History, clinical evidence, suspicion or significant risk, for thromboembolic events, as well as myocardial infarction, stroke, and/or antiphospholipid syndrome and any participants requiring antithrombotic treatment
• History or current hypogammaglobulinemia
• Serious systemic viral, bacterial or fungal infection
• Participants with a history of invasive opportunistic infections, such as, but not limited to histoplasmosis, listeriosis, coccidioidomycosis, candidiasis, pneumocystis jirovecii, and aspergillosis, regardless of resolution
• Evidence of active or untreated latent tuberculosis as documented by medical history (eg, chest Xrays) and examination, and tuberculosis testing
• High dose of steroids, or a change in dose within 4 weeks prior to randomization
• High dose of antimalarial, or a change in dose within 12 weeks prior to randomization
• High dose of immunosuppressants or a change in dose within 12 weeks prior to randomization
• Use of cyclophosphamide within 3 months prior to screening
• Previous parenteral (IV), intramuscular (IM), or intra-articular steroid administration within 4 weeks prior to randomization
• Participants likely to require multiple courses of oral corticosteroid (OCS) during the study for chronic diseases other than SLE
• Administration of any live (attenuated) vaccine within 3 months prior to randomization (eg, varicella zoster vaccine, oral polio, rabies)
• Administration of any non-live vaccine (eg, seasonal influenza, COVID-19) within 4 weeks prior to randomization

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05039840
• Other Study ID Numbers: ACT17010; 2021-001567-25 ( EudraCT Number ); U1111-1266-5011 ( Registry Identifier: ICTRP )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

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/

• Responsible Party: Sanofi
• Study Sponsor: Sanofi
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: October 2021