An open-label study to assess safety, efficacy and cellular kinetics of YTB323 in severe, refractory systemic lupus erythematosus (srSLE).

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

28 Feb 2023 → ongoing

Decision date (initial)

2024-05-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-510081-27-00

EudraCT number

2022-001796-14

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenetic, Pharmacogenomic, Safety, Pharmacokinetic, Pharmacodynamic

To assess safety of YTB323 in participants with srSLE.

Secondary objectives 5

1. To characterize the in vivo cellular kinetics (pharmacokinetics, PK) of YTB323 in peripheral blood by quantitative polymerase chain reaction (qPCR).
2. To characterize the incidence and prevalence of pre-existing and treatment induced immunogenicity (cellular and humoral) of YTB323.
3. To evaluate feasibility of the manufacturing process in srSLE.
4. Part A: To assess the effect of YTB323 on the following 000 disease activity scores
5. Part A: To evaluate effect of YTB323 for srSLE participants who also have active 00000000000000

Conditions and MedDRA coding

Systemic Lupus Erythematosus.

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Signed informed consent.
2. Adequate renal, hepatic, cardiac, hematological and pulmonary function.
3. Men and women with SLE, aged ≥18 years and ≤65 years at screening, fulfilling the 2019 European League Against Rheumatism EULAR/ACR classification criteria for SLE.
4. Patient must be positive for at least one of the following autoantibodies at screening: antinuclear antibodies (ANA) at a titer of ≥1:80, or anti dsDNA (above the ULN); or anti-Sm (above the ULN).
5. Active (severe) disease as defined by SLEDAI-2K ≥8 (not including the SLEDAI-2K domains of lupus headache, cerebrovascular accident, organic brain syndrome*) AND at least one of the following significant SLE related organ involvements that can result in debilitating and permanent damage or may represent a life-threatening condition as judged by the investigator and defined by: - Renal - At least moderate or severe peri/myocarditis - At least moderate or severe pleuritis or other lung involvement - Vasculitis
6. 000000000000000000

Exclusion criteria 12

1. Clinically significant active, opportunistic, chronic or recurrent infection confirmed by clinical evidence, imaging, or positive laboratory tests (e.g., blood cultures, PCR for DNA/RNA, such as COVID-19 etc.) one month prior to or during screening. Patients who have had at least one severe infection that required prolonged hospitalization in the intensive care setting within 5 years prior to screening and/or at least one severe infection that required prolonged hospitalization within one year prior to screening.
2. Uncontrolled diabetes mellitus, lung diseases or any other illness that are not related to SLE that in the opinion of the Investigator would jeopardize the ability of the patient to tolerate lymphodepletion and CD19 CAR T cell therapy.
3. Prior history of malignancy except for localized basal cell or squamous skin cancer. Other malignancies for which the patient is judged to be cured for at least 5 years by local surgical therapy, such as head and neck cancer, or stage I breast cancer will be considered on an individual basis.
4. Any patients requiring medications prohibited by the protocol.
5. Any psychiatric condition or disability compliance with treatment or informed consent impossible.
6. Prior treatment with anti-CD19 therapy, adoptive T cell therapy or any prior gene therapy product (e.g. CAR-T cell therapy).
7. History of bone marrow/hematopoietic stem cell or solid organ transplantation.
8. Female participants who are pregnant or breastfeeding or intending to conceive during the course of the study.
9. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using a highly effective method of contraception starting from the time of enrollment to at least 12 months (24 months in the US) after the YTB323 administration (unless local regulations mandate a longer duration) and until CAR-T cells are no longer present by qPCR on two consecutive tests.
10. Sexually active males unwilling to use a condom during intercourse from the time enrollment for at least 12 months after YTB323 administration and until CAR-T cells are no longer present by qPCR on two consecutive tests.
11. Any acute, severe lupus related 0000000 during screening that needs immediate treatment and/or makes the immunosuppressive washout impossible; thus, makes the patient ineligible for CD19 CAR-T therapy as judged by the Investigator,00000000000
12. 000000000000.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety parameters include vital signs, adverse events, laboratory parameters and ECG evaluation.

Secondary endpoints 6

1. YTB323 transgene concentration by qPCR over time in peripheral blood; cellular kinetics parameters (Cmax, AUC, Tmax, T1/2, Clast, Tlast).
2. Pre-existing and treatment induced immunogenicity (cellular, humoral) of YTB323.
3. Manufacture success (defined as meeting release specification and at or above the planned target dose).
4. At various timepoints: - SLEDAI-2K - Physician's global assessment - LLDAS - Remission (DORIS)
5. UPCR at various timepoints.
6. Complete Renal Response (CRR) at various timepoints.

Investigational products

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

Test 1

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 10

Locations

3 EU/EEA countries · 12 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 35 files

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

Application history

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