A Study to Evaluate the Safety and Activity of SAR448501/DR-0201 in Patients With Autoimmune Rheumatic Diseases

A Phase 1, Open-label, Multiple Ascending Dose Basket Study to Evaluate the Safety and Activity of SAR448501/DR-0201 in Patients With Select Autoimmune Rheumatic Diseases

This is an open-label, multi-ascending dose (MAD) phase 1 study, with dose expansion at selected doses, in adult patients with select autoimmune rheumatic diseases including systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). The purpose of the study is to identify possible optimal dose(s) by assessing the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary clinical response of SAR448501/DR-0201.

The study duration per participant will be a minimum of approximately 13 months, including a screening period of up to 28 days, a treatment period of 71 days, and a follow-up period of 42 weeks. If necessary, participants will continue to have visits after End of Study (EOS) every 4 weeks until peripheral blood B cells return to at least 80% of either the lower limit of normal (LLN) or the participant's baseline value.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus (SLE); Rheumatoid Arthritis (RA)
• Intervention / Treatment: Drug: SAR448501

• Study Type: Interventional
• Enrollment (Estimated): 62
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free for US & Canada); Phone Number: option 6 800-633-1610; Email: contact-us@sanofi.com

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia, 4151
      • Recruiting
      • Investigational Site Number : 001-203
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • Investigational Site Number : 001-201
• Bosnia and Herzegovina
  • Sarajevo, Bosnia and Herzegovina, 71000
    • Recruiting
    • Investigational Site Number : 001-401
• New Zealand
  • Auckland, New Zealand, 0622
    • Recruiting
    • Investigational Site Number : 001-301
• South Africa
  • Pretoria, South Africa, 0002
    • Recruiting
    • Investigational Site Number : 001-801
  • Pretoria, South Africa, 0184
    • Recruiting
    • Investigational Site Number : 001-803
  • Vereeniging, South Africa, 1935
    • Recruiting
    • Investigational Site Number : 001-804

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of SLE and/or RA. American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria should be used.
• Contraception during the study intervention period and for at least 140 days after the last administration of study intervention: Male participants must agree to refrain from donating or cryopreserving sperm, and either be abstinent or use contraception/barrier. Female participants must use of a highly effective contraceptive measure for all females of childbearing potential. Females of childbearing potential need to have a negative serum pregnancy test within 7 days prior to the first dose.

• Specific to Systemic Lupus Erythematosus (SLE):

  • Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) score ≥8 at screening with at least 4 points from clinical features at screening.
  • At least 1 British Isles Lupus Assessment (BILAG) A score or 1 BILAG B score at screening
  • Positive ANA (titer ≥1:80) as documented in the participant's medical history
  • Positive for any of the following as documented in the participant's medical history: antidsDNA, anti-Ro (anti-SS-A), anti-La (anti-SS-B), or anti-Sm antibodies
  • Inadequate response to systemic glucocorticoids and to at least 1 therapy other than antimalarials for at least 12 weeks including: cyclophosphamide, mycophenolate mofetil or its derivatives, belimumab, azathioprine, anifrolumab, methotrexate, rituximab, obinutuzumab, cyclosporin, tacrolimus, or voclosporin.

• Specific to Rheumatoid Arthritis (RA):

  -- Moderate-to-severe disease activity as defined by a 28-joint disease activity score using C reactive protein (DAS28-CRP) >3.2 at screening.

• Inadequate response or intolerance to at least 2 disease-modifying antirheumatic drugs (DMARDs, at least 1 biologic [bDMARD] or targeted synthetic [tsDMARD]) after a minimum of 12 weeks treatment duration.
• At least 6 tender joints at screening.
• At least 6 swollen joints at screening.
• Methotrexate (MTX) for at least 12 consecutive weeks, and at a stable dose of ≤25 mg/week oral or SC since at least 4 weeks prior to randomization, OR - in case of MTX intolerance - conventional DMARDs at a stable dose for at least 28 days.
• If taking MTX, compliant with folic acid 1 mg daily or 5 mg weekly or greater in combination with MTX.

Exclusion Criteria:

• Severe manifestation of the selected autoimmune rheumatic diseases under study that could impact participant safety, or is likely to require interventions that will affect investigational drug PD.
• Receipt of super-high potency (eg, clobetasol propionate, betamethasone dipropionate) or high potency (eg, fluocinonide, methylprednisolone aceponate) topical corticosteroids within 28 days prior to screening, had dose changes in other topical corticosteroids within 14 days prior to Day 1, or had dose changes in nonsteroidal topical immunosuppressants within 28 days prior to Day 1.
• Received dose changes of mycophenolate mofetil, methotrexate, leflunomide, calcineurin inhibitors, JAK inhibitors, or azathioprine within 28 days prior to Day 1.
• Receipt of any of the following medications within 6 months of Day 1: cyclophosphamide, leflunomide >20 mg/day, abatacept.
• Receipt of any mAb or experimental immunomodulator within 28 days or 5 published half-lives prior to Day 1, whichever is longer.
• Receipt of rituximab or other B cell depleting biologics within 6 months of Day 1.
• Receipt of rituximab or other B cell depleting biologics without return of CD19 or CD20 count to above the LLN.
• Receipt of alemtuzumab, bone marrow transplantation, stem cell transplantation, total lymphoid irradiation, CAR-T or T cell vaccination therapy.
• Known history of a primary immunodeficiency or an underlying condition such as known human immunodeficiency virus (HIV) infection, positive result for HIV infection, splenectomy, or any underlying condition that predisposes the participant to infection.
• History of a hypersensitivity reaction or anaphylaxis to a previous mAb or human immunoglobulin therapy.
• Active infection or a history of serious infections as defined in the protocol.
• Surgery within 28 days prior to Day 1.
• 12-lead ECG parameters after 10 minutes resting in supine position NOT in the defined normal ranges.
• Evidence of significant, uncontrolled concurrent disease that could affect compliance with the study (eg, chronic obstructive pulmonary disease).
• Diagnosis or history of malignant disease within 5 years prior to baseline, with the exceptions of basal cell or squamous epithelial carcinomas of the skin that have been resected or cervical carcinoma in situ, with no evidence of recurrence within the 5 years prior to baseline.
• High dose of antimalarial or a change in dose within 28 days prior to Day 1.
• Receipt of systemic corticosteroids >20 mg/day (prednisone or equivalent) or had dose changes of systemic corticosteroids within 28 days prior to Day 1.
• Documented liver disease including documented diagnosis of cirrhosis.
• Participants with a history of hypercoagulation event or thrombosis (such as venous thromboembolism, pulmonary embolism, or stroke), or participants who have known hypercoagulation risk factors (including antiphospholipid syndrome), or participants currently on anticoagulation will be excluded.

• Specific to SLE:

  • 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 at screening.
  • Known biopsy-proven diagnosis of lupus nephritis (any class) or otherwise unexplained proteinuria (0.5g protein/24h; or urine protein/creatinine ratio >0.5g/g) at screening.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAR448501 dose escalation; SAR448501 will be administered for up to 71 days. Different cohorts with up to 7 dose levels will be included.	Drug: SAR448501; Bispecific antibody; Other Names: DR-0201

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events (TEAEs)		Baseline to Week 52 (End of Study (EOS))
Incidence of potentially clinically significant abnormalities (PCSAs)	PCSAs include laboratory parameters; vital signs; and ECG parameters including heart rate, PR, QRS, QT, QTcF.	Baseline to Week 52 (EOS)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of pharmacokinetic (PK) parameters: AUC0-t	Area under the plasma concentration versus time curve calculated using the trapezoidal method during a dosing interval (t)	Baseline to Week 20
Assessment of pharmacokinetic (PK) parameters: Cmax	Maximum observed plasma concentration	Baseline to Week 20
Assessment of pharmacokinetic (PK) parameters: Ctrough	Concentration observed before treatment administration during repeated dosing	Baseline to Week 20
Incidence of anti-drug antibodies (ADAs)	Incidence of ADAs against SAR448501/DR-0201	Baseline to Week 16

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2025
• Primary Completion (Estimated): June 25, 2029
• Study Completion (Estimated): June 25, 2029

Study Registration Dates

• First Submitted: October 16, 2024
• First Submitted That Met QC Criteria: October 16, 2024
• First Posted (Actual): October 17, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid
• Other Study ID Numbers: DR-0201-AIM-001; DR0201AIM001 (Other Identifier: Sanofi Identifier); U1111-1328-5055 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No