A clinical trial to learn about the effects of YTB323 in people with difficult-to-treat severe inflammatory myopathies (IIM)

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

4 Feb 2025 → ongoing

Decision date (initial)

2024-12-20

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: Efficacy, Safety

To demonstrate the superiority of rapcabtagene autoleucel at a target dose of xx CAR-positive viable T cells, as a single infusion, over comparator (Investigator choice of treatment) with respect to achieving moderate to major improvement in the Total Improvement Score (TIS) at Week 52 for xx

Secondary objectives 10

1. To demonstrate the superiority of rapcabtagene autoleucel over comparator with respect to: 1. achieving moderate to major improvement (TIS ≥ 40) at Week 52 for participants xx
2. To demonstrate the superiority of rapcabtagene autoleucel over comparator with respect to: 2. reducing cumulative use of glucocorticoids from baseline to Week 52 xx
3. To demonstrate the superiority of rapcabtagene autoleucel over comparator with respect to: 3. improving pulmonary function at Week 52 xx
4. To demonstrate the superiority of rapcabtagene autoleucel over comparator with respect to: 4. achieving major improvement (TIS ≥ 60) at Week 52 xx
5. To demonstrate the superiority of rapcabtagene autoleucel over comparator with respect to: 5. reducing fatigue at Week 52 xx
6. To demonstrate the superiority of rapcabtagene autoleucel over comparator with respect to: 6. reducing cumulative use of glucocorticoids from baseline to Week 52 xx
7. To demonstrate the superiority of rapcabtagene autoleucel over comparator with respect to: 7. improving pulmonary function at Week 52 xx
8. To demonstrate the superiority of rapcabtagene autoleucel over comparator with respect to: 8. achieving major improvement (TIS ≥ 60) at Week 52 xx
9. To demonstrate the superiority of rapcabtagene autoleucel over comparator with respect to: 9. reducing fatigue at Week 52 xx
10. To evaluate the overall safety and tolerability of rapcabtagene autoleucel.

Conditions and MedDRA coding

Severe refractory idiopathic inflammatory myopathies (IIM)

Regulatory references

Scientific advice from competent authorities

Norwegian Medical Products Agency

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. Signed informed consent must be obtained prior to participation in the study
2. Male or female participants xx on the day of signing informed consent.
3. A diagnosis of probable or definite myositis according to American College of Rheumatology/European League Against Rheumatism 2017 (ACR/EULAR 2017) criteria.
4. Participant must be xx based on an historical result xx
5. Participants must have refractory xx:a. xx b. xx i. xx ii.xx iii. Xx iv. xx xx
6. Diagnosed with active disease such as presence of at least 1 of the following criteria and confirmed by an adjudication committee for criteria b through e prior to randomization: xx

Exclusion criteria 5

1. Have severe muscle damage at Screening, as defined xx
2. Participants treated with RTX xx prior to Screening or CYC xx prior to Baseline.
3. Inadequate organ function (one retest during Screening of any of the below is permitted): Inadequate renal function (performed by central laboratory) defined as: • eGFR < 45 ml/min/1.73m2 using the 2021 CKD-EPI formula. Inadequate hepatic function defined as any of the following: • ALT and AST >1.5 × ULN (performed by central laboratory), except if clinically assessed as secondary to IIM • Total Bilirubin >1.5 × ULN (performed by central laboratory). Participants with Gilbert's syndrome may be included if their total bilirubin is ≤ 3.0 × ULN and direct bilirubin ≤1.5 × ULN. • International normalized ratio (INR) >1.5 (performed by central laboratory) Inadequate cardiac function defined as: • Left ventricular ejection fraction (LVEF) <50% as determined by echocardiogram (ECHO) Inadequate hematologic function (performed by central laboratory) defined as: • Absolute neutrophil count (ANC) <1500/mm3 • Platelets <100,000/μL • White blood cells count (WBC) <3,000 cells/μL • Absolute lymphocyte count <700/μL • Hemoglobin < 8.0 g/dL (< 4.9 mmol/L) Inadequate pulmonary function defined by ANY of the following: • Oxygen saturation measured by pulse xx • Hemoglobin corrected DLCO xx • FVC% xx
4. Any participant who failed all available treatment options in the comparator arm or for whom these options are clinically inappropriate in the opinion of the Investigator.
5. Hypersensitivity and/or contraindications to any product (including its ingredients) to be given to the participant as per the study protocol (e.g., rapcabtagene autoleucel, comparator arm treatments, tocilizumab, xx, etc.), to the excipients of rapcabtagene autoleucel (e.g., xx), or to any other drug product as advised for administration in the study protocol (e.g., xx, G-CSF , tocilizumab).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Achieving moderate to major improvement in TIS (TIS ≥ 40) at Week 52 (Yes/No)

Secondary endpoints 6

1. Achieving moderate to major improvement in TIS (≥ 40) at Week 52 (Yes/No)
2. Adjusted annual cumulative GC dose up to Week 52
3. Change from baseline in percent predicted Forced Vital Capacity (FVC%) at Week 52
4. Achieving major improvement in TIS (≥ 60) at Week 52 (Yes/No)
5. Change from baseline in Patient-Reported Outcome Measurement Information System (PROMIS)-Fatigue 7a at Week 52
6. Safety parameters include vital signs, adverse events, laboratory parameters and ECG evaluation

Investigational products

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

Test 1

Comparator 6

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 27

Locations

5 EU/EEA countries · 37 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

Serious breaches 1 · Art. 52 CTR

Temporary halts 4 · Art. 38 CTR

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 85 files

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

Application history

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