Last Update: Oct 08, 2024
A Randomized, Double-blind 2-arm NEPTUNUS Extension Study to Assess the Long-term Safety and Efficacy of Ianalumab in Patients With Sjogrens Syndrome.
ClinicalTrials.gov Identifier:
Novartis Reference Number:CVAY736A2301E1
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

The purpose of this study is to measure the long-term safety and tolerability of
ianalumab in participants with Sjogrens syndrome who have previously completed treatment
from one of two NEPTUNUS 1 year core studies (CVAY736A2301 or CVAY736A2302).

- The study treatment is ianalumab 300 mg in a 2 mL pre-filled syringe for injection.
All participants will receive ianalumab either monthly or every 3 months.

- The treatment duration will be 3 years with an additional up to 2-year safety
follow-up. The total duration of this extension study will be up to 5 years.

- The visit frequency will be monthly during both the treatment period and mandatory
follow-up, and then less frequently during the subsequent conditional follow-up

Treatment of interest: The randomized treatment (ianalumab) will be received monthly or
every 3 months. Participants assigned to treatment every 3 months will receive placebo
every month between the ianalumab doses to maintain blinding.

Number of Participants: Approximately 600 participants from the NEPTUNUS core studies
will be rolled over into the extension study.

Treatment Groups: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.

From Week 52 of the NEPTUNUS core studies (i.e., Day 1 in the extension study), eligible
participants will be assigned to either one of the treatment regimens:

- ianalumab 300 mg monthly or

- ianalumab 300 mg once every 3 months Participants receiving placebo in either of the
NEPTUNUS core studies will be randomized 1:1 to receive ianalumab 300 mg monthly or
every 3 months starting from Week 60 and participants receiving ianalumab in either
of the NEPTUNUS core studies will continue the same treatment in the extension
study.

Ianalumab will be given as a subcutaneous injection from a 2 mL pre-filled syringe.
Participants will be given the opportunity to self-inject at home on some visits after
receiving training. The primary purpose of this 3-year treatment extension study is the continued evaluation
of the safety and tolerability of treatment with ianalumab 300 mg monthly or every 3
months. An additional purpose is to explore the long-term efficacy of both dosing
regimens of ianalumab 300 mg.

The Primary Objective is to assess the long-term safety and tolerability of ianalumab in
participants with Sjogrens syndrome. Secondary objectives are as follows, To evaluate the
long-term efficacy of VAY736 300 mg administered monthly or every 3 months.

To show comparability of ianalumab Ctrough between 2x 1mL PFS (from the NEPTUNUS core
studies: CVAY736A2301 and CVAY736A2302) and 1x 2mL PFS for participants on continuous
monthly treatment.

To further assess the pharmacokinetics of ianalumab. To assess the impact of long-term
treatment on B-cell depletion. Trial Design: This is a multicenter, randomized,
double-blind, phase 3b study to assess the long-term safety and tolerability of four
treatment regimens of ianalumab in participants with Sjogrens 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 continue their assigned treatment to receive
ianalumab 300 mg either monthly or every 3 months for up to 3 additional years of
treatment beyond the 1-year core study period. 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.

Study Population: Participants with Sjogrens syndrome who have completed treatment in one
of two NEPTUNUS core studies.

Method of blinding: Double-blind Study treatment assignment method: Participants
randomized to ianalumab 300 mg monthly or every 3 months in one of the NEPTUNUS core
studies will continue their assigned treatment. Participants randomized to placebo in the
NEPTUNUS core studies will be randomized in a 1:1 ratio to either ianalumab 300 mg
monthly or every 3 months.

Participants randomized to ianalumab 300 mg every 3 months will receive placebo (a dummy
treatment) once monthly between doses.

Committees: An independent Data Monitoring Committee (DMC) will be utilized for safety
review throughout the study. A steering committee will be formed to ensure overview of
the study conduct.

Sjogrens Syndrome
Phase3
Recruiting
600
Oct 27, 2023
Jul 18, 2030
All
18 Years - 75 Years (Adult, Older Adult)

Interventions

Drug

Ianalumab (VAY736)

VAY736 300 mg /2 mL, PFS, Solution for injection for subcutaneous use
Other

Placebo

Placebo 0 mg/2 mL, PFS, Solution for injection for subcutaneous Use

Eligibility Criteria

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 (lactating) 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, unless they are using highly effective methods of
contraception 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.

- Female bilateral tubal ligation, female sterilization (have had surgical
bilateral oophorectomy with or without hysterectomy) or total hysterectomy at
least six weeks before taking study treatment. In case of oophorectomy alone,
only when the reproductive status of the woman has been confirmed by follow up
hormone level assessment.

- Male sterilization (at least 6 months prior to screening). For female
participants on the study, the vasectomized male partner should be the sole
partner for that participant.

- Use of oral (estrogen and progesterone), injected, or implanted hormonal
methods of contraception or placement of an intrauterine device (IUD) or
intrauterine system (IUS), or other forms of hormonal contraception that have
comparable efficacy (failure rate < 1%), for example hormone vaginal ring or
transdermal hormone contraception.

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.

Women are considered post-menopausal if they have had 12 months of natural
(spontaneous) amenorrhea with an appropriate clinical profile (e.g., age-appropriate
history of vasomotor symptoms). Women are considered of not child-bearing potential
if they are post-menopausal or have had surgical bilateral oophorectomy (with or
without hysterectomy), total hysterectomy or bilateral tubal ligation at least six
weeks ago. In the case of oophorectomy alone, only when the reproductive status of
the woman has been confirmed by follow-up hormone level assessment is she considered
not of child-bearing potential.

If local regulations deviate from the contraception methods listed above to prevent
pregnancy, local regulations apply and will be described in the informed consent
form (ICF).

5. Sexually active males unless they agree to use barrier protection during intercourse
while taking study treatment are excluded. As condom use alone has a reported
failure rate exceeding 1% per year, it is recommended 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.

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