Phase 2, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of daxdilimab in patients with active, proliferative lupus nephritis (LN).
Approximately 210 participants will be randomized to receive daxdilimab or placebo administered subcutaneously through Week 52 in addition to their standard of care background therapy (mycophenolate mofetil (MMF) and corticosteroids). At Week 64, all participants will be assigned to a quarterly dosing maintenance regimen of either daxdilimab or placebo based upon pre-defined renal response observed by Week 52. The maximum trial duration per participant is approximately 116 weeks including a 4-week screening period, the 104 weeks for the treatment period where participants will receive daxdilimab or placebo, and approximately 8 weeks for the follow-up period. Safety evaluations will be performed regularly throughout the course of the study. Acquired from Horizon in 2024.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
19
Daxdilimab will be administered subcutaneously as two injections for each dose. Other Names: HZN-7734
Daxdilimab will be administered subcutaneously as two injections for each dose. Other Names: HZN-7734
Placebo will be administered subcutaneously as two injections for each dose.
Percentage of Participants Who Achieved CRR at Week 48 Through Week 52
CRR was defined as meeting all of the following: * Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m\^2 or no worse than 15% below Baseline * 24-hour urine protein to creatinine ratio (UPCR) ≤ 0.5 mg/mg * No discontinuation of trial intervention or use of restricted medication beyond the protocol-allowed threshold before assessment
Time frame: Week 48 to Week 52
Percentage of Participants Who Achieved Overall Renal Response (ORR) at Week 48 Through Week 52
CRR was defined as meeting all of the following: * EGFR ≥ 60 mL/min/1.73 m\^2 or no worse than 15% below Baseline * 24-hour UPCR ≤ 0.5 mg/mg * No discontinuation of trial intervention or use of restricted medication beyond the protocol-allowed threshold before assessment Partial renal response (PRR) was defined as meeting all of the following: * EGFR ≥ 60 mL/min/1.73 m\^2 or no worse than 15% below Baseline * Improvement in 24-hour UPCR: * For participants with a Baseline UPCR ≤ 3.0 mg/mg: \< 1.0 mg/mg * For participants with a Baseline UPCR \> 3.0 mg/mg: \> 50% improvement from baseline and ≤ 3.0 mg/mg * No discontinuation of trial intervention or use of restricted medication beyond the protocol-allowed threshold before assessment
Time frame: Week 48 to Week 52
Change From Baseline in eGFR at Week 52
Change over time in the levels of eGRF present in the blood.
Time frame: Baseline and Week 52
Proportion of Participants Achieving a Decrease in Daily Oral Corticosteroid (OCS) Dose of ≤ 2.5 mg Prednisone-Equivalent by Week 24 Maintained Through Week 52
Sustained reduction of OCS dose: * Prednisone-equivalent dose ≤ 2.5 mg/day by Week 24 and not exceeding this dose through Week 52 and * No discontinuation of trial intervention or use of restricted medication beyond the protocol-allowed threshold before assessment
Time frame: Week 24 to Week 52
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Serum Concentration of Daxdilimab
Levels of daxdilimab present in the blood serum at different time points.
Time frame: Week 0 pre-dose, and 6 hours post-dose; Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, and Week 36
Number of Participants With Detectable Anti-Drug Antibodies (ADA) Against Daxdilimab
Assessed via blood test at multiple time points throughout the duration of the study.
Time frame: Up to approximately 36 weeks
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
An AE was any untoward medical occurrence in a participant or clinical subject who was administered a pharmaceutical product, which may or may not have been causally related to the treatment. A serious AE (SAE) was any AE resulting in death, life-threatening situations, inpatient hospitalization or its prolongation, persistent/significant disability/incapacity, congenital abnormality/birth defect, or other significant medical events that may have jeopardized the participant or required medical/surgical intervention to prevent the outcomes listed above. Treatment-emergent AEs of special interest (AESI) included hypersensitivity reactions (e.g., anaphylaxis), severe viral infections/reactivations (Common Terminology for Adverse Events \[CTCAE\] Grade 3+), herpes zoster, opportunistic infections, and malignancies.
Time frame: Up to approximately 36 weeks