Biopsy Based Study to Understand Mechanism of Action of Ianalumab in Salivary Glands and Explore Relationships with Clinical Assessments

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 Jul 2022 → 5 Jan 2026

Decision date (initial)

2024-03-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-508957-24-00

EudraCT number

2020-005055-20

ClinicalTrials.gov

NCT05124925

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacodynamic, Safety, Pharmacokinetic, Pharmacogenetic

To investigate changes in salivary gland histopathology after treatment with ianalumab

Secondary objectives 5

1. To evaluate the safety and tolerability of ianalumab
2. To characterize changes in salivary gland tissue by multimodal salivary gland ultrasound (SGUS) after treatment with ianalumab
3. To assess the pharmacokinetics (PK) of ianalumab
4. To assess the immunogenicity (IG) of ianalumab
5. To investigate changes in stimulated and unstimulated salivary flow rate after treatment with ianalumab

Conditions and MedDRA coding

Sjögren's syndrome

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002338-PIP03-21

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Written informed consent must be obtained before any assessment is performed.
2. Male and female patients 18 years of age or older at Screening.
3. Classification of Sjögren's syndrome according to the 2016 ACR/EULAR criteria at screening.
4. Seropositive at screening for anti-Ro/SSA antibodies
5. Screening EULAR Sjögren’s syndrome patient reported index (ESSPRI) score ≥ 5
6. Able to communicate well with the investigator, to understand and comply with the requirements of the study.

Exclusion criteria 23

1. Use of other investigational drugs within 5 half-lives of enrollment or within 30 days whichever is longer, or longer if required by local regulations
2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes (e.g., mAb of IgG1 class) or to any of the constituents of the study drug formulation
3. Required regular use of medications known to cause dry mouth/eyes as a regular and major side effect, and which have not been on a stable dose for at least 30 days prior to Screening, or any anticipated change in the treatment regimen during the course of the study
4. History of head and neck radiation therapy or of having received radioactive iodine
5. Any surgical, medical (e.g. uncontrolled hypertension, heart failure or diabetes) psychiatric or additional physical condition that the investigator feels may jeopardize the patient in case of participation in this study
6. People deprived of their liberty by a judicial or administrative decision (Article L 1121-6 of the French Public Health Code)
7. Receipt of live/attenuated vaccine within a 4-week period prior to baseline
8. History of primary or secondary immunodeficiency, or a positive HIV (ELISA and Western blot) test result
9. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin, in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
10. Presence of another autoimmune rheumatic disease that is active and constitutes the principal illness.
11. Any one of the following screening values of CBC laboratory values: - Hemoglobin levels below 8.0 g/dL - Total leukocyte count less than 2,000/μL - Platelets <50 x 109/L (if between 50 and 80, the PI should check that it is linked to Sjögren’s syndrome and not to any other disease) - Absolute neutrophil count (ANC) <1.0 x 109/L (one re-test is allowed during the screening period)
12. Evidence of patients with history of or may become eligible according to national guidelines)
13. 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 hCG laboratory test
14. Participants not registered in the social security system
15. Participants within the exclusion period of a preceding study
16. Use of topical ocular prescription medications (excluding artificial tears, gels, lubricants) that have not been on a stable dose for at least 90 days prior to treatment, or any anticipated change in the treatment regimen during the course of the study
17. Prior use of ianalumab
18. History of receiving: o Any B-cell depleting therapies, other than ianalumab (e.g., rituximab, other anti-CD20 mAb, anti-CD22 mAb, or anti-CD52 mAb) administered within 36 weeks prior to randomization, or as long as B cell count is less than the lower limit of normal or baseline value prior to receipt of B cell-depleting therapy (whichever is lower).
19. Current use of prednisone >10 mg/day [or equivalent other corticosteroid] or dose change within 2 weeks prior to dosing
20. Prior treatment with any of the following within 6 months of baseline: - CTLA4-Fc Ig (abatacept), - Anti-TNF-α mAb, - Intravenous Ig, - Plasmapheresis, - i.v. or oral cyclophosphamide, - i.v. or oral cyclosporine A, - Iscalimab (anti-CD40), - Belimumab (anti-BAFF mAb)
21. Patients taking either hydroxychloroquine more than 400 mg/day or methotrexate more than 25 mg weekly or leflunomide at not stable dose within 3 months prior to dosing. Patients who are taking the above-mentioned drugs can be included if dose is within the mentioned limits and maintained at stable dose throughout the study
22. Active viral, bacterial or other infections.
23. History of major organ, hematopoietic stem cell or bone marrow transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in logarithm of salivary gland B/B+T cell ratio at Week 25 (EOT)

Secondary endpoints 5

1. Occurrence of treatment emergent adverse events (both serious and non-serious) during the study and occurrence of treatment emergent abnormal vital signs, laboratory and ECG data over the study period.
2. Change from baseline in SGUS parameters over the study period
3. Serum ianalumab concentrations during treatment and follow up. PK parameters AUCtau, AUClast, AUCinf, Cmax, Tmax, T1/2 after the last dose (if data permits) and any other parameters as required
4. Serum anti-ianalumab antibody (ADA assay) and incidence of ADA positive patients over the study period
5. Change from baseline in mean stimulated and unstimulated salivary flow rate changes over the study period

Investigational products

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

Test 1

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

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 13

Locations

1 EU/EEA country · 1 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 13 files

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

Application history

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