A randomized, double-blind, parallel group, placebo-controlled multicenter study to evaluate efficacy, safety and tolerability of ianalumab in participants with diffuse cutaneous systemic sclerosis

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

2 Jan 2025 → ongoing

Decision date (initial)

2024-10-25

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Safety, Efficacy

To demonstrate the superiority of ianalumab, compared to placebo, in achieving 3/5 Revised Composite Response Index in Systemic Sclerosis 25 (rCRISS25) response at Week 52

Secondary objectives 6

1. To demonstrate the superiority of ianalumab, compared to placebo, on change from baseline in percent-predicted forced vital capacity (FVC%) at Week 52.
2. To demonstrate the superiority of ianalumab, compared to placebo, on change from baseline in modified Rodnan Skin Score (mRSS) at Week 52.
3. To demonstrate the superiority of ianalumab, compared to placebo, on change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 52
4. To assess the pharmacokinetics of ianalumab
5. To evaluate the immunogenicity of ianalumab
6. To assess the overall safety and tolerability of ianalumab

Conditions and MedDRA coding

Diffuse cutaneous systemic sclerosis (dcSSc)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, Paul-Ehrlich-Institut

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. Male and female participants ≥ 18 and ≤ 70 years (at the time of the screening visit).
2. Diagnosis of systemic sclerosis, as defined by the 2013 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) classification criteria for SSc (van den Hoogen et al 2013) and meet the dcSSc subset classification according to LeRoy (LeRoy et al 1988)
3. Disease duration of ≤ 60 months (defined as time from the first non-Raynaud phenomenon manifestation, e.g., puffy hands, scleroderma, digital ulcers, arthralgia, dyspnea)
4. mRSS units of ≥ 15 and ≤ 45 at the time of the screening visit
5. Active disease that meets at least one of the following criteria at screening: • Disease duration of ≤ 18 months defined as time from the first non−Raynaud phenomenon manifestation • Increase in mRSS of ≥ 3 units compared with the most recent assessment performed within the previous 6 months • Invoed within the previous 6 months • Involvement of one new body area and an increase in mRSS of ≥ 2 units compared with the most recent assessment performlvement of two new body areas within the previous 6 months • Elevated acute phase reactants (ESR) ≥ 30 mm/hr or high-sensitivity C-reactive protein (hsCRP) ≥ 6 mg/L) • Presence of SSc-interstitial lung disease (ILD) and ATA autoantibody positivity • Modified EUSTAR disease activity index (mDAI) ≥ 2.5
6. Participant must be positive for at least one of the following autoantibodies: • anti-topoisomerase I (ATA) (also known as anti-SCL-70) • anti-RNA polymerase III (anti-RNAP3) • anti-nuclear antibody (ANA) (≥ 1:80) Participants who are positive only for ANA (while being negative for both ATA /anti-RNAP3) will be limited to 30% of the overall randomized study population.

Exclusion criteria 11

1. Rheumatic disease other than dcSSc, including limited cutaneous disease (lcSSc) or sine scleroderma at the screening visit. Secondary Sjogren's disease and scleroderma myopathy are not exclusionary.
2. Treatment with biologic agents, such as intravenous immunoglobulin or monoclonal antibodies, including marketed drugs, within 12 weeks or 5 half-lives (whichever is longer) prior to baseline visit, unless explicitly allowed in inclusion criteria
3. Treatment with any investigational agent within ≤ 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of the baseline visit
4. Use of anti-fibrotic agents including colchicine, D-penicillamine, pirfenidone, or tyrosine kinase inhibitors (e.g., nintedanib, nilotinib, imatinib, dasatinib) in the 4 weeks prior to baseline visit. Patients with SSc-ILD requiring antifibrotics for management of ILD during the study, as per investigator judgement, should be excluded
5. Previous treatment with chlorambucil, bone marrow transplantation or total lymphoid irradiation.
6. Positive anti-centromere antibody (ACA+) without positive ATA or anti-RNAP3 autoantibody result at the screening visit
7. Previous improvement (decrease) in mRSS > 10 units
8. Pulmonary disease with FVC ≤ 50% of predicted or diffusing capacity of the lung for carbon monoxide (DLCO, corrected for hemoglobin) ≤ 40% of predicted at the screening visit
9. WHO Functional Class 3 or higher assessment for pulmonary arterial hypertension (PAH, as defined on right heart catheterization), receiving IV therapy for PAH or evidence of other moderately severe pulmonary disease
10. Participants treated with cyclophosphamide within 12 weeks prior to Baseline.
11. Prior use of a B-cell depleting therapy 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)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 3/5 rCRISS25 response at Week 52

Secondary endpoints 6

1. Change from baseline in FVC% predicted at Week 52.
2. Change from baseline in mRSS at Week 52.
3. Change from baseline in HAQ-DI at Week 52.
4. Ianalumab concentrations in serum during treatment and Follow-up Period
5. Incidence and titer of anti-drug (ianalumab) antibodies (ADAs) in serum over time
6. Safety evaluation includes adverse events, laboratory parameters, and vital signs

Investigational products

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

Test 1

Placebo 1

Auxiliary 4

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 23

Locations

10 EU/EEA countries · 38 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

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

Documents 188 files

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

Application history

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