Study of Safety, Efficacy and Tolerability of Secukinumab Versus Placebo, in Combination With SoC Therapy, in Patients With Active Lupus Nephritis
- Registration Number
- NCT04181762
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
This was a pivotal, randomized, double-blind, placebo-controlled trial evaluating at Week 52 the efficacy and safety of secukinumab versus placebo in patients with active lupus nephritis (ISN/RPS Class III or IV, with or without co-existing class V features) also receiving background standard of care therapy (SoC).
- Detailed Description
The study consisted of the following parts:
* Screening (up to 42 days/6 weeks)
* Run-in period (optional): For subjects who received Mycophenolic acid (MPA) as SoC induction therapy as per investigator's decision and who were not already on MPA at Screening, MPA dosing was initiated during a run-in period before Randomization (for up to 4 weeks prior to the first dose of secukinumab)
* Treatment Period: Duration of 104 weeks of treatment with secukinumab/placebo in addition to SoC treatment (with last dose given at Week 100)
* Secukinumab dosing was started with initial dosing of 300 mg s.c. injections at Baseline, Weeks 1, 2, 3, and 4, followed by dosing every 4 weeks
* Follow-up period: Duration of 8 weeks (last visit performed 12 weeks after last dose of study medication) for all except for subjects entering extension study CAIN457Q12301E1 (NCT05232864).
A total of 275 subjects were enrolled and were randomized to secukinumab 300 mg (n = 137) or placebo (n = 138) until study termination. Recruitment in this study was stopped on 26-May-2023. The CAIN457Q12301 study was terminated early by Novartis due to futile results from interim analysis 1 (IA1). There was no safety related reasons for early termination or concerns for the subjects in the study. The decision was made to terminate both the core and the related extension study in view of treatment futility of the core study.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 275
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description secukinumab secukinumab A blinded, weekly, subcutaneous (s.c.) secukinumab 300 mg loading regimen was administered for the first 4 weeks followed by a monthly maintenance dose in all randomized subjects thereafter. placebo Placebo A blinded, weekly, subcutaneous (s.c.) matching placebo loading regimen was administered for the first 4 weeks followed by a monthly maintenance dose in all randomized subjects thereafter.
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving Complete Renal Response (CRR) at Week 52 Baseline, Week 52 Complete Renal Response (CRR) is a composite endpoint defined as:
* Estimated Glomerular Filtration Rate (eGFR) \>= 60 mL/min/1.73 m\^2 or no less than 85% of core Baseline values and
* 24-hour Urine-to-Protein Creatinine Ratio (UPCR) =\< 0.5mg/mg
* No treatment discontinuation before Week 52
* The subject did not receive more than 10 mg/day prednisone or equivalent for \>= 3 consecutive days or for \>= 7 days in total during Week 44 through Week 52.
Non-responder imputation (NRI) was used for participants who did not have the required data to compute responses at Week 52 or who had discontinued study treatment before Week 52. A logistic regression model was used for the analysis of this endpoint.
- Secondary Outcome Measures
Name Time Method Change From Baseline in 24-hour Urine Protein-to Creatinine Ratio (UPCR) Baseline, Week 52 Urine Protein-to-Creatinine Ratio (UPCR) was determined by a central laboratory by dividing the protein concentration by the creatinine concentration as measured in the urine collected (24-hour urine collection sample).
Percentage of Participants Achieving Partial Renal Response (PRR) at Week 52 Baseline, Week 52 Partial Renal Response (PRR) is a composite endpoint defined as:
* \>= 50% reduction in 24-hour Urine-to-Protein Creatinine Ratio (UPCR) to sub-nephrotic levels (=\< 3 mg/mg) and
* Estimated Glomerular Filtration Rate (eGFR) \>= 60 mL/min/1.73 m\^2 or no less than 85% of BaselineAverage Daily Dose of Oral Corticosteroids Week 16 to Week 52 Average daily dose of oral corticosteroids doses was used to assess efficacy of secukinumab compared to placebo in the averaged daily dose of oral corticosteroids administered between Week 16 and Week 52.
Percentage of Participants Achieving Partial Renal Response (PRR) at Week 24 Baseline, Week 24 Partial Renal Response (PRR) is a composite endpoint defined as:
* \>= 50% reduction in 24-hour Urine-to-Protein Creatinine Ratio (UPCR) to sub-nephrotic levels (=\< 3 mg/mg) and
* Estimated Glomerular Filtration Rate (eGFR) \>= 60 mL/min/1.73 m\^2 or no less than 85% of BaselineIncidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52 Baseline to Week 52 Time to achieve Complete Renal Response (CRR) up to week 52 was evaluated by 4-week interval by using Kaplan-Meier estimates. Participants who did not achieve CRR were censored at the date of their last non-missing CRR result (including participants who completed week 52 without achieving CRR).
* Subjects at risk = Subjects who did not achieve CRR and were not censored before or at the start of the specified interval. Participants had an event when achieving CRR.
* Incidence rate (%) = (number of subjects with event/number of subjects at risk) x 100.Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52 Baseline to Week 52 Time to achieve Partial Renal Response (PRR) up to week 52 was evaluated by 4-week interval by using Kaplan-Meier estimates. Participants who did not achieve PRR were censored at the date of their last non-missing PRR result (including participants who completed week 52 without achieving PRR). Participants had event when achieving PRR.
* Subjects at risk = Subjects who did not achieve PRR and were not censored before or at the start of the specified interval.
* Incidence rate (%) = (number of subjects with event/ number of subjects at risk) x 100.Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52 Baseline to Week 52 Time to achieve first morning void Urine Protein-to-Creatinine Ratio (UPCR) \<= 0.5 mg/mg up to week 52 was evaluated by 4-week interval by using Kaplan-Meier estimates. Participants who did not achieve UCPR were censored at the date of their last non-missing UCPR result (including participants who completed week 52 without achieving UCPR). Participants had event when achieving UCPR.
* Subjects at risk = Subjects who did not achieve UCPR and were not censored before or at the start of the specified interval.
* Incidence rate (%) = (number of subjects with event/ number of subjects at risk) x 100.Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Mean Change From Baseline up to Week 52 Baseline, Week 12, Week 24, Week 36, Week 52 The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the past week. The purpose of the FACIT-Fatigue in this study was to assess the impact of fatigue on subjects with lupus nephritis (LN). The level of fatigue was measured on a 5-point Likert scale (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much) based on their experience of fatigue during the past 2 weeks. The scale score is computed by summing the item scores, after reversing those items that are worded in the negative direction. FACIT-Fatigue scale score range from 0 to 52, where higher scores represent less fatigue.
Short Form Health Survey (SF-36) Version 2 (Acute Form) Mean Change From Baseline in Physical Component Score (PCS) up to Week 52 Baseline, Week 12, Week 24, Week 36, Week 52 The SF-36 questionnaire consists of eight scales yielding two summary measures: physical and mental health. The physical health measure includes four scales of physical functioning (10 items), role-physical (4 items), bodily pain (2 items), and general health (5 items). The mental health measure is composed of vitality (4 items), social functioning (2 items), role-emotional (3 items), and mental health (5 items). In this trial, SF-36-PCS responder (improvement of \>= 2.5 points) were evaluated. Responses to items allow for direct calculation of scale scores, while the physical component summary (PCS) scores are computed from weighted scale scores. For all scales and summary measures, higher scores indicate better health outcomes (PCS scores range 0 to 100).
Lupus Quality of Life (LupusQoL) Physical Health Score Mean Change From Baseline up to Week 52 Baseline, Week 12, Week 24, Week 36, Week 52 The LupusQoL is a disease-specific, 34-item, self-report questionnaire designed to measure the health-related quality of life (HRQoL) of subjects with SLE within 8 domains (i.e., physical health (8 items), emotional health (6 items), body image (5 items), pain (3 items), planning (3 items), fatigue (4 items), intimate relationships (2 items), and burden to others (3 items)). Responses are based on a 5-point Likert scale where 0 (all of the time) to 4 (never). Each domain of the LupusQoL was scored separately. Transformed scores range from 0 (worst HRQoL) to 100 (best HRQoL).
Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) From first dose of study treatment up to approximately 2 years The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
Percentage of Participants With Complete Renal Response (CRR) at Week 104 Within Those Who Had Achieved CRR at Week 52 in the Secukinumab Group Week 52 to Week 104 The percentage of participants with maintained renal response (CRR) at Week 104 in the secukinumab group was evaluated
Percentage of Participants With Improved or Maintained Response (PRR or CRR) at Week 104 in Those Who Had Achieved at Least PRR at Week 52 in the Secukinumab Group Week 52 to Week 104 The percentage of participants with improved or maintained renal response (CRR) at Week 104 in the secukinumab group was evaluated
Trial Locations
- Locations (9)
University Of Alabama
🇺🇸Birmingham, Alabama, United States
Kaiser Permanente Fontana
🇺🇸Fontana, California, United States
University of California LA
🇺🇸Los Angeles, California, United States
Arthritis and Rheum Dise Spec
🇺🇸Aventura, Florida, United States
Integral Rheumatology and Immunology Specialists IRIS
🇺🇸Plantation, Florida, United States
Piedmont Heart Institute
🇺🇸Atlanta, Georgia, United States
Beth Israel Deaconess Hospital
🇺🇸Boston, Massachusetts, United States
Ahmed Arif Medical Research Center
🇺🇸Grand Blanc, Michigan, United States
Novartis Investigative Site
🇻🇳Ho Chi Minh, Vietnam