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

Plain English Summary

A Study to Evaluate the Safety and Activity of SAR448501/DR-0201 in Patients With Autoimmune Rheumatic Diseases is a Phase 1 clinical trial sponsored by Sanofi studying Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA). This study tests the safety and effectiveness of a new drug called SAR448501/DR-0201. It is for adults with certain autoimmune rheumatic diseases, specifically Systemic Lupus Erythematosus (SLE) or Rheumatoid Arthritis (RA). Participants will receive the study drug, and their health will be closely monitored. The study involves regular visits over approximately 13 months. Alternative treatments include existing medications for SLE and RA, such as other disease-modifying drugs and biologics. The trial aims to enroll 62 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults diagnosed with Systemic Lupus Erythematosus (SLE) or Rheumatoid Arthritis (RA) can join. Patients must have active disease that has not responded well to at least one previous treatment. Specific disease activity scores and antibody levels are required for eligibility. Individuals with severe disease manifestations, recent use of certain medications, active infections, or a history of certain cancers may not be eligible. This trial is studying Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure how safe the drug is by tracking any side effects and unexpected health issues that arise during the study. The specific primary outcome measures are: Incidence of treatment-emergent adverse events (TEAEs) (Baseline to Week 52 (End of Study (EOS))); Incidence of potentially clinically significant abnormalities (PCSAs) (Baseline to Week 52 (EOS)). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial is important because it explores a new treatment option for patients with autoimmune rheumatic diseases like lupus and rheumatoid arthritis who have not responded to existing therapies. This research targets Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), where improved treatment options are needed.

Investor Insight

This Phase 1 trial is an early step to assess a new drug, indicating potential for future treatments in the autoimmune disease market, which is substantial. Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the study drug, potential side effects, and how it might interact with your current medications. Participation involves regular clinic visits for drug administration, blood tests, and health assessments over about 13 months. You will need to use effective contraception during the study and for a period afterward. This trial is currently recruiting participants. The trial is being conducted at 8 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 62 participants

Interventions

• DRUG: SAR448501 — Bispecific antibody

Primary Outcomes

• Incidence of treatment-emergent adverse events (TEAEs) (Baseline to Week 52 (End of Study (EOS)))
• Incidence of potentially clinically significant abnormalities (PCSAs) (Baseline to Week 52 (EOS))

Secondary Outcomes

• 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)

Full Eligibility Criteria

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.
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Trial Locations

• Investigational Site Number : 001-203, Brisbane, Queensland, Australia
• Investigational Site Number : 001-201, Melbourne, Victoria, Australia
• Investigational Site Number : 001-402, Mostar, Bosnia and Herzegovina
• Investigational Site Number : 001-401, Sarajevo, Bosnia and Herzegovina
• Investigational Site Number : 001-301, Auckland, New Zealand
• Investigational Site Number : 001-801, Pretoria, South Africa
• Investigational Site Number : 001-803, Pretoria, South Africa
• Investigational Site Number : 001-804, Vereeniging, South Africa

Frequently Asked Questions

Related Conditions

• Systemic Lupus Erythematosus (SLE)
• Rheumatoid Arthritis (RA)
• Autoimmune Diseases
• Immunology
• Inflammatory Diseases
• Connective Tissue Diseases
• Vasculitis
• Sjogren's Syndrome
• Scleroderma
• Polymyositis/Dermatomyositis

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