A Randomized, Double-blind 2-arm, Followed by an Open-label 1-arm, NEPTUNUS Extension Study to Assess the Long-term Safety and Efficacy of Ianalumab in Patients With Sjogrens Syndrome. (NEPTUNUS-Ext)

Novartis

Status and phase: Active, not recruiting; Phase 3

Conditions: Sjogrens Syndrome

Treatments: Other: Placebo; Drug: Ianalumab (VAY736)

Study type: Interventional

Funder types: Industry

Identifiers

NCT05985915

CVAY736A2301E1

2022-502966-26 (EudraCT Number)

Details and patient eligibility

About

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]).

Full 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.

Enrollment: 612 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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 exclusion criteria in Section 5.2 for details).

2. Plans for administration of live vaccines during the study period.

3. Pregnant or nursing (breastfeeding) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human Chorionic Gonadotropin (hCG) laboratory test.

4. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, from menarche until becoming post-menopausal, unless they have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral salpingectomy at least six weeks before taking study treatment. In the case of oophorectomy alone, the reproductive status of the woman needs to have been confirmed by follow-up hormone level assessment. Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., hormonal profile confirming menopause and/or age-appropriate history of vasomotor symptoms).

   WOCBP are excluded unless they are using highly effective methods of contraception (failure rate < 1% per year) while taking study treatment during dosing and for 6 months after stopping of investigational drug. Highly effective contraception methods include:

   • Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post- ovulation methods) and withdrawal are not acceptable methods of contraception.
   • Bilateral tubal occlusion or bilateral tubal ligation (at least six weeks before taking study treatment).
   • Sterilization (vasectomy) of male partner (s) of the female participant at least 6 months prior to screening provided partner(s) has(have) received medical confirmation of surgical process.
   • Use of hormonal contraception methods:
   • Combined (estrogen and progestogen-containing) hormonal contraception associated with inhibition of ovulation; oral, intravaginal or transdermal.
   • Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable or implantable.
   • Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS) In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.

   Contraception should be used in accordance with locally approved prescribing information of concomitant medications administered.

   If local regulations are more stringent than the contraception methods listed above, local regulations apply and will be described in the informed consent form (ICF).

5. United States (and other countries, if male contraception is locally required): Sexually active males, unless they agree to use barrier protection during intercourse with a woman of child-bearing potential, while taking study treatment. As condom use alone has a reported failure rate exceeding 1% per year, it is recommended that female partners of male study participants use a second method of birth control. Although ianalumab is not teratogenic and/or genotoxic, and not transferred to semen, male contraception is required, as requested by FDA.

Globally, for all sexually active males, contraception should be used in accordance with the locally approved prescribing information of concomitant medications administered.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

612 participants in 2 patient groups

Ianalumab Monthly

Experimental group

Description:

Ianalumab 300 mg s.c. monthly during initial double-blind treatment period. Open-label treatment and receive ianalumab 300 mg monthly.

Treatment:

Drug: Ianalumab (VAY736)

Ianalumab 3 Monthly

Experimental group

Description:

Ianalumab 300 mg s.c. every three months and placebo once monthly between doses during initial double-blind treatment period. Open-label treatment and receive ianalumab 300 mg monthly.

Treatment:

Drug: Ianalumab (VAY736)

Other: Placebo