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.
• 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.