Sjogrens Syndrome
Conditions
Keywords
Sjogrens Syndrome, ianalumab, VAY736, NEPTUNUS
Brief summary
The purpose of this study is to measure the long-term safety and tolerability of ianalumab in participants with Sjögren's syndrome who have previously completed treatment from one of two NEPTUNUS 1 year core studies (CVAY736A2301 \[NCT05350072\] or CVAY736A2302 \[NCT05349214\]).
Detailed description
This is a multicenter, randomized, double-blind, followed by an open-label, phase 3 study to assess the long-term safety and tolerability of of 300 mg ianalumab s.c. injection in participants with Sjögren's syndrome who have taken part in and completed one of two NEPTUNUS core studies, NEPTUNUS-1 (CVAY736A2301) or NEPTUNUS-2 (CVAY736A2302). There will be no screening period in this trial. From Week 48 of the NEPTUNUS core study, participants will be given the opportunity to consent to this extension study. Eligible participants will enter the double blind treatment period and receive ianalumab 300 mg either monthly or every three months, consistent with their prior treatment assignment. Participants previously randomized to placebo in the core studies will be randomized 1:1 to receive ianalumab 300 mg monthly or every three months, starting at Week 60. Participants assigned to every three month dosing will receive monthly placebo injections between active doses to maintain blinding. The study treatment is ianalumab 300 mg in a 2 mL pre-filled syringe (PFS) in needle safety device for injection or ianalumab via 2 mL autoinjector (AI). An AI is a device constituent of a single integral, or single entity, drug-device combination product, with drug primary mode of action. Participants already enrolled into the study (before AI approval and implementation) will continue receiving the treatment via PFS and will not be switched to AI. All participants, including those previously on ianalumab 300 mg every three months or monthly in the double-blind treatment period will switch to open-label treatment and receive ianalumab 300 mg monthly. The treatment duration including both double-blind and open-label treatment periods will be 6 years. After the treatment period, all participants will enter a follow-up period to be monitored for at least 20 weeks and then a conditional (if B-cell recovery criteria have not been met) follow-up period. The total post treatment follow-up period is up to 2 years. The total duration of this extension study will be up to 8 years.
Interventions
DRUGIanalumab (VAY736)
Ianalumab 300 mg / 2 mL, PFS or AI, monthly or every 3 months, solution for injection for subcutaneous use
OTHERPlacebo
Placebo 0 mg/2 mL PFS or AI, once monthly between doses of Ianalumab 3 monthly , solution for injection for subcutaneous Use
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent prior to participation in the extension study. 2. Participants must have participated in either one of the two NEPTUNUS core studies, CVAY736A2301 or CVAY736A2302, and must have completed the entire treatment up to Week 48 without treatment discontinuation in core NEPTUNUS studies. 3. In the judgement of the Investigator, participants must be expected to clinically benefit from continued ianalumab therapy.
Exclusion criteria
1. Use of therapies excluded by the NEPTUNUS-1 and NEPTUNUS-2 study protocols (see NEPTUNUS studies protocols
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment-emergent AEs (TEAEs)/SAEs | Week 52 to Week 464 | Assessment of safety and tolerability of ianalumab (VAY736) in patients with active Sjogrens syndrome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants achieving ≥ 5 points reduction from baseline in ESSDAI | Over time up to Week 360 | EULAR Sjogren's syndrome disease activity index (ESSDAI) is a validated clinical disease outcome measure for Sjogrens that will be used in the study The instrument contains 12 organ-specific domains contributing to assessment of disease activity. For each domain, features of disease activity are scored by a clinician in 3 or 4 (Level 0=No disease activity to Level 3= high disease activity) levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score. The maximum possible score is 123.To calculate ESSDAI, all 12 organ domains must be individually assessed by a trained assessor (study Investigator) at every scheduled timepoint. This is to evaluate the long-term efficacy of VAY736 300 mg administered monthly or every 3 months. |
| Percentage of participants achieving ≥2.3 points reduction from baseline in ESSPRI among participants with baseline ESSPRI ≥3 score over time | Over time up to Week 360 | The EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) questionnaire consists of three items to be given an activity level score between 0-10: pain (joint and/or muscle pain), fatigue and dryness (0 = no symptom at all and 10 = worst symptom imaginable ESSPRI is an established disease outcome measure for Sjogrens. It consists of three domains of dryness, pain and fatigue. The participant will assess severity of symptoms they experience on a single 0-10 numerical scale for each of the three domains. The ESSPRI score is defined as a mean of scores from the three scales: (dryness + pain + fatigue) /3. |
| Percentage of participants achieving ≥2.0 points reduction from baseline in SSSD among participants with baseline SSSD ≥3 | Over time up to Week 360 | The Sjogrens Syndrome Symptom Diary (SSSD) questionnaire consists of five (six for females) questions about symptoms of Sjögren's syndrome, each question given a score of 0-10 (0=no symptoms, 10=worst possible symptoms) where patient choose the one response that best describes how severe the symptom was at its worst in the PAST 24 HOURS. It includes six symptom items (eye dryness, mouth dryness, skin dryness, physical fatigue, muscle and/or joint pain, genital dryness), and applies a recall period of 24 hrs. The aim of the SSSD is to establish patient reported endpoints for the treatment of Sjogrens syndrome. Participants will complete the diary daily for 7 days prior to the scheduled dosing. |
| Pre-dose Ianalumab serum concentrations | pre-dose at Week 48 (from core study) and Week 64 | To show comparability of ianalumab Ctrough between 2x 1 mL PFS (from the NEPTUNUS core studies) and 1x 2 mL PFS for participants on continuous monthly treatment. |
| On-treatment Ianalumab serum concentrations | During treatment (from Week 52 to Week 204) and follow-up (From Week 208 to Week 304) | To further assess the pharmacokinetics of ianalumab. |
| B-cell count measurement | Week 52 to Week 304 | To assess impact of long-term treatment on B-cell depletion. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czechia, France, Germany, Greece, Guatemala, Hungary, India, Israel, Italy, Japan, Lithuania, Mexico, Poland, Portugal, Romania, Singapore, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed