An Open-label Extension Study to Assess the Efficacy and Safety of Ianalumab With or Without Study Treatment Withdrawal in Adult Participants With Lupus Nephritis Who Have Completed Study Treatment in the CVAY736K12301 Core Study (SIRIUS-LN Extension)
Overview
- Phase
- Phase 3
- Intervention
- Ianalumab
- Conditions
- Lupus Nephritis
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 315
- Locations
- 26
- Primary Endpoint
- For cohort 1: Incidence of renal flare, escalation of immunosuppressive medication, or death
- Status
- Recruiting
- Last Updated
- last month
Overview
Brief Summary
The purpose of this 2-year extension study is the evaluation of the efficacy and safety
- after study treatment withdrawal in patients with lupus nephritis (LN) who achieved response (complete renal response [CRR] or partial renal response [PRR]) on double-blind treatment at the end of the SIRIUS-LN core study, and
- of open-label ianalumab 300 mg treatment in patients who, at the end of the SIRIUS-LN core study, were either already receiving ianalumab open-label treatment or did not meet CRR/PRR criteria on double-blind treatment at the end of the SIRIUS-LN core study.
Detailed Description
The SIRIUS-LN extension study is a 2-year open-label extension study for participants who have completed the treatment periods (blinded Treatment Period-1 and blinded Treatment Period-2) of the SIRIUS-LN core study on double-blind or open-label study treatment. Investigators will use their clinical judgment to decide if it is beneficial for participants to continue with the extension study. In this extension study participants who achieve CRR or PRR status at Week 140 will be withdrawn from study treatment and will maintain the SoC medication as required. These 2 additional years in the extension study will allow to measure sustained remission, flares and safety off-study treatment. However, in the event of renal flares during the extension study, these participants who withdraw study treatment will have the option to receive open-label ianalumab.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed informed consent prior to participation in the extension study.
- •Participants must have participated in the SIRIUS-LN core study and must have completed the entire treatment up to Week 144 on double-blind or open label study treatment.
Exclusion Criteria
- •Use of prohibited therapies
- •Pregnant or nursing (lactating) women.
Arms & Interventions
Open-Label Ianalumab (cohort 2)
(Cohort 2): Open-Label Ianalumab group: Participants who received blinded study treatment throughout the core study and did not achieve CRR or PRR at Week 140 of the core study, or who had switched to open-label ianalumab during the core study, will be eligible or will continue to receive open-label ianalumab in the extension study.
Intervention: Ianalumab
Study Treatment Withdrawal (cohort 1)
(Cohort 1): Study Treatment-Withdrawal group. Participants who received blinded study treatment in the core study and achieve CRR or PRR at Week 140 in the core study will enter the extension study and discontinue study treatment while maintaining standard of care (SoC) medication, as required. If renal flare criteria are met, participants will be eligible to receive open-label ianalumab.
Outcomes
Primary Outcomes
For cohort 1: Incidence of renal flare, escalation of immunosuppressive medication, or death
Time Frame: Between Week 144E1 and Week 248
Cohort 1: To estimate the incidence of renal flare, escalation of immunosuppressive medication, or death following study treatment withdrawal in participants who completed the SIRIUS-LN core study on double-blind treatment and achieved CRR or PRR at Week 140 of the core study
Cohort 2: Number of participants with Treatment Emergent Adverse Events (TEAE) as assessed by CTAE v4.0
Time Frame: From the start of treatment in the SIRIUS-LN core study to EOS (up to week 352) of the extension study
Cohort 2: To assess the safety and tolerability of ianalumab for participants who, at the end of the SIRIUS-LN core study, were either already receiving ianalumab open-label treatment or did not meet CRR/PRR criteria on double-blind treatment at the end of the SIRIUS-LN core study
Cohort 2: Number of participants with Serious Adverse Events (SAE) as assessed by CTCAE v4.0
Time Frame: From the start of treatment in the SIRIUS-LN core study to EOS (up to week 352) of the extension study
Cohort 2: Incidence of SAEs, from the start of treatment in the SIRIUS-LN core study to EOS (up to week 352) of the extension study
Cohort 2: Number of participants with clinically significant abnormal vital signs
Time Frame: From the start of treatment in the SIRIUS-LN core study to EOS (up to week 352) of the extension study
Cohort 2: Analysis of the vital sign measurements using summary statistics for the change from baseline for each post-baseline visit will be performed
Cohort 2: Number of participants with clinically significant laboratory evaluations.
Time Frame: From the start of treatment in the SIRIUS-LN core study to EOS (up to week 352) of the extension study
Cohort 2: The summary of laboratory evaluations will be presented for two groups of laboratory tests (hematology and serum chemistry). Descriptive summary statistics for the change from baseline to each study visit will be presented. These descriptive summaries will be presented by test group, laboratory test and treatment group.
Secondary Outcomes
- Cohort 1: Number of participants with Treatment Emergent Adverse Events (TEAE) as assessed by CTCAE v4.0(From the start of treatment in the SIRIUS-LN core study up to EOS (week 248) of the extension study)
- Cohort 2: Incidence and titer of anti-ianalumab antibodies in serum (ADA assay)(from Week 144E1 up to Week 248)
- Cohort 2: Ianalumab concentration in serum using a validated ELISA(from Week 144E1 up to Week 248)
- Cohort 1: Number of participants with Serious Adverse Events (SAE) as assessed by CTAE v4.0(From the start of treatment in the SIRIUS-LN core study up to EOS (week 248) of the extension study)
- Cohort 1: Number of participants with clinically significant abnormal vital signs(From the start of treatment in the SIRIUS-LN core study up to EOS (week 248) of the extension study)
- Cohort 1: Number of participants with clinically significant abnormal laboratory evaluations(From the start of treatment in the SIRIUS-LN core study up to EOS (week 248) of the extension study)