A randomized, double-blind 2-arm NEPTUNUS extension study to assess the long-term safety and efficacy of ianalumab in patients with Sjögren’s syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

27 Oct 2023 → ongoing

Decision date (initial)

2023-10-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novartis Pharma AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Therapy, Pharmacodynamic, Dose response, Safety

To assess the long-term safety and tolerability of ianalumab in participants with Sjögren’s syndrome

Secondary objectives 4

1. To evaluate the long-term efficacy of ianalumab xxx mg administered monthly or every 3 months
2. To show comparability of ianalumab Ctrough between 2x 1 mL PFS (from the NEPTUNUS core studies: CVAY736A2301 and CVAY736A2302) and 1x 2 mL PFS for participants on continuous monthly treatment
3. To further assess the pharmacokinetics of ianalumab
4. To assess impact of long-term treatment on B-cell depletion

Conditions and MedDRA coding

Sjögren’s syndrome

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002338-PIP03-21

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

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 the core NEPTUNUS studies.
3. In the judgement of the Investigator, participants must be expected to clinically benefit from continued ianalumab therapy.

Exclusion criteria 5

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 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. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of treatment-emergent AEs (TEAEs)/SAEs

Secondary endpoints 6

1. ESSDAI change from baseline
2. Proportion of participants achieving ≥1 point reduction from baseline or ≥15% reduction from baseline in ESSPRI score over time up to Week 204
3. Proportion of participants achieving meaningful improvement in the SSSD score over time up to Week 204
4. Ianalumab serum concentrations collected pre-dose (i.e., Ctrough) at Week 48 (from core studies) and Week 64
5. Ianalumab serum concentrations during treatment (e.g., Ctrough) and follow-up after last dose
6. B-cell count measurement

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel Town

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 20

Locations

16 EU/EEA countries · 76 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 164 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications