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

NCT06647069 | Recruiting Phase 1 DMC

• 3 other identifiers: DR-0201-AIM-001DR0201AIM001U1111-1328-5055
• Study Type: interventional
• Target: 62
• Locations: 4 countries
• Sites: 8

Brief Summary

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.

Conditions

Systemic Lupus Erythematosus (SLE); Rheumatoid Arthritis (RA)

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Assessment of pharmacokinetic (PK) parameters: AUC0-t

  Baseline to Week 20

• Assessment of pharmacokinetic (PK) parameters: Cmax

  Baseline to Week 20

• Assessment of pharmacokinetic (PK) parameters: Ctrough

  Baseline to Week 20

• Incidence of anti-drug antibodies (ADAs)

  Baseline to Week 16

Study Arms (1)

SAR448501 dose escalation

EXPERIMENTAL

SAR448501 will be administered for up to 71 days. Different cohorts with up to 7 dose levels will be included.

Drug: SAR448501

Interventions

SAR448501 DRUG

Bispecific antibody

Also known as: DR-0201

SAR448501 dose escalation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (8)

Investigational Site Number : 001-203

Brisbane, Queensland, 4151, Australia

RECRUITING

Investigational Site Number : 001-201

Melbourne, Victoria, 3004, Australia

RECRUITING

Investigational Site Number : 001-402

Mostar, 88000, Bosnia and Herzegovina

RECRUITING

Investigational Site Number : 001-401

Sarajevo, 71000, Bosnia and Herzegovina

RECRUITING

Investigational Site Number : 001-301

Auckland, 0622, New Zealand

RECRUITING

Investigational Site Number : 001-801

Pretoria, 0002, South Africa

RECRUITING

Investigational Site Number : 001-803

Pretoria, 0184, South Africa

RECRUITING

Investigational Site Number : 001-804

Vereeniging, 1935, South Africa

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Central Study Contacts

Trial Transparency email recommended (Toll free for US & Canada)

CONTACT

800-633-1610; Contact-US@sanofi.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2024
• First Posted: October 17, 2024
• Study Start: March 27, 2025
• Primary Completion (Estimated): June 25, 2029
• Study Completion (Estimated): June 25, 2029
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

ZA (3); BO (2); NZ (1); AU (2)