A clinical trial to learn about the effects of YTB323 in people with difficult to treat severe diffuse cutaneous systemic sclerosis (dcSSc)

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

10 Dec 2024 → ongoing

Decision date (initial)

2025-02-23

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-510380-34-00

WHO UTN

U1111-1309-0489

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To demonstrate the superiority of rapcabtagene autoleucel at a target dose of CAR-positive viable T cells as a single infusion compared to rituximab, with respect to the proportion of participants achieving a Revised Composite Response Index in Systemic Sclerosis 50 (rCRISS50) response at Week 52

Secondary objectives 2

1. To demonstrate the efficacy of rapcabtagene autoleucel versus rituximab with respect to disease progression parameters
2. To assess the overall safety and tolerability of rapcabtagene autoleucel in participants with dcSSc

Conditions and MedDRA coding

Diffuse cutaneous systemic sclerosis (dcSSc)

Regulatory references

Scientific advice from competent authorities

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 3

1. Participant must fulfill the 2013 American College of Rheumatology/ European League Against Rheumatism classification criteria for systemic sclerosis (van den Hoogen et al 2013) and meet the diffuse cutaneous SSc (dcSSc) subset classification according to LeRoy (LeRoy et al 1988)
2. Disease onset from the first non-Raynaud symptoms attributable to SSc (e.g., puffy hands, scleroderma, digital ulcers, arthralgia, dyspnea) within 7 years prior to the Screening visit
3. Severe, progressive systemic sclerosis disease defined by at least one of the following: • Progressive systemic sclerosis-associated interstitial lung disease • Severe, progressive systemic sclerosis skin disease • Clinically significant systemic sclerosis-associated cardiac involvement at Screening

Exclusion criteria 8

1. Any condition during Screening that could prevent a complete washout of medications as required per protocol or could otherwise make the participant ineligible for anti-CD19 CAR-T therapy and further participation in the study, as judged by the Investigator
2. Participants with history of hypersensitivity to excipients in rapcabtagene autoleucel or to rituximab
3. Any participant for whom treatment with rituximab is clinically inappropriate in the opinion of the investigator
4. Any medical conditions that are not related to SSc that, in the opinion of the Investigator, would jeopardize the ability of the participant to tolerate lymphodepletion and anti-CD19 CAR-T cell therapy
5. Rheumatic disease other than dcSSc, (except secondary Sjogren’s syndrome or scleroderma myopathy), including limited cutaneous systemic sclerosis (lcSSc) or sine scleroderma at Screening
6. Participants with pre-existing pulmonary hypertension.
7. Significant renal pathology at Screening, including: • Scleroderma renal crisis • Confirmed diagnosis of glomerulonephritis
8. Participants with uncontrolled stage II hypertension at Screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Achievement of a treatment response as per the rCRISS50 definition at Week 52

Secondary endpoints 4

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. Safety evaluation includes adverse events, laboratory parameters, vital signs, ECGs, and mortality

Investigational products

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

Test 1

Comparator 2

Auxiliary 3

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 17

Locations

10 EU/EEA countries · 66 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 176 files

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

Application history

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