A Study to Evaluate the Safety and Activity of SAR448501/DR-0201 in Patients With Autoimmune Rheumatic Diseases
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-75
SponsorSanofi
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
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
Disqualifiers
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.
Trial design
Design model
Sequential
Treatments tested in this trial
SAR448501
DrugBispecific antibody
Treatment groups
62 Participants
are divided into 1 treatment groupGroup A: SAR448501 dose escalationExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Incidence of treatment-emergent adverse events (TEAEs)
Time frame
Baseline to Week 52 (End of Study (EOS))2
Incidence of potentially clinically significant abnormalities (PCSAs)
PCSAs include laboratory parameters; vital signs; and ECG parameters including heart rate, PR, QRS, QT, QTcF.
Time frame
Baseline to Week 52 (EOS)Secondary outcomes
1
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)
Time frame
Baseline to Week 202
Assessment of pharmacokinetic (PK) parameters: Cmax
Maximum observed plasma concentration
Time frame
Baseline to Week 203
Assessment of pharmacokinetic (PK) parameters: Ctrough
Concentration observed before treatment administration during repeated dosing
Time frame
Baseline to Week 204
Incidence of anti-drug antibodies (ADAs)
Incidence of ADAs against SAR448501/DR-0201
Time frame
Baseline to Week 16 Source ClinicalTrials.gov