2.1.1.1 Clinical trial identifiers

EU trial number:

2024-519592-26-00

Full title (English):

Treatment of patients with autoantibody-positive autoimmune diseases and severe interstitial lung fibrosis with T lymphocytes transduced by RV-SFG.CD19.CD28.4-1BBzeta retroviral vector - a single center Phase I/II clinical trial (HD-CAR-ILD-1)

Public title (English):

Treatment of patients with autoantibody-positive autoimmune diseases and severe interstitial lung fibrosis with T lymphocytes transduced by RV-SFG.CD19.CD28.4-1BBzeta retroviral vector - a single center Phase I/II clinical trial (HD-CAR-ILD-1)

Protocol code:

HD-CAR-ILD-1

2.1.1.2 Secondary identifying numbers

WHO universal trial number (UTN):

ClinicalTrials.gov identifier (NCT number):

ISRCTN number:

2.1.1.3 Additional registries

2.1.2.1 Transition Trial

EudraCT number:

2.1.2.2 Trial Category

Trial phase:

Human Pharmacology (Phase I)- Other

Trial category:

2

Justification for trial category:

Phase I, Category includes safety and efficacy trials in patients

2.1.2.3 Medical Conditions

Medical condition(s) (English):

Therapy-resistant and progressing lung fibrosis in the course of an autoantibody-positive autoimmune disease like Systemic Sclerosis, ANCA-associated Vasculitis, seropositive Rheumatoid Arthritis, Sjögren’s disease, anti-Synthetase Syndrome or other autoimmune diseases

Is the medical condition considered to be a rare disease:

Yes

Therapeutic area:

Diseases [C] - Immune System Diseases [C20]

2.1.2.4 Medical condition(s) MedDRA information

Version	Level	Classification code	Term name	System organ class
21.0	LLT	10025109	Lung involvement in systemic sclerosis	10038738
21.1	PT	10068801	Antisynthetase syndrome	100000004859
23.1	LLT	10040107	Seropositive rheumatoid arthritis	10028395
21.0	LLT	10025088	Lung fibrosis	10038738
28.0	LLT	10086756	ANCA-associated vasculitis	100000004848

2.1.2.5 Main objective

Trial scope:

Safety, Therapy, Other, Efficacy

Main objective (English):

Primary objective of HD-CAR-ILD-1 is to assess the feasibility of CD19.CAR.T cell treatment in patients with autoantibody-positive autoimmune diseases and severe interstitial lung fibrosis with T lymphocytes transduced by RV-SFG.CD19.CD28.4-1BBzeta retroviral vector

2.1.2.6 Secondary objective

Secondary objective number	Secondary objective (English)
1	Safety (i. e. toxicities)
2	Efficacy (clinical response as indicated by an improvement of lung function)

2.1.2.7 Principal inclusion criteria

Inclusion criteria number	Principal inclusion criteria (English)
1	Confirmed autoantibody-positive autoimmune-triggered lung fibrosis with im-paired pulmonary function of FVC < 70% (but >40%) and TLCO/VA <60% (but >25%) and/or TLCO SB <60% (but >25%), in the course of diseases like Rheumatoid Arthritis, Systemic Sclerosis, ANCA-associated vasculitis, anti-Synthetase Syndrome, Sjögren’s disease or other autoimmunopathies.
2	Adequate organ function: - Renal function defined as: serum creatinine of ≤ 2 x ULN or eGFR ≥ 30 mL/min/1.73 m2 - Liver function defined as: • ALT ≤ 3 times the ULN for the respective age • Bilirubin ≤ 2.0 mg/dl with the exception of patients with hyper-bilirubinemia explained by Gilbert–Meulengracht Syndrome (may be included if total bilirubin is ≤ 3.0 x ULN and direct bili-rubin ≤ 1.5 x ULN) - minimum level of pulmonary reserve defined as ≤ grade 2 dyspnea and pulse oxygenation > 85% on room air and functional vital capacity FVC > 40% - Hemodynamic stability and LVEF ≥ 40% as confirmed by echocardi-ogram - In case of moderate or severe pulmoarterial hypertension: combina-tion therapy with at least 2 approved drugs (according to routine care) is mandatory
3	Absolute neutrophil count (ANC) ≥ 1000/mm3
4	Absolute lymphocyte count (ALC) ≥ 400/mm3
5	Age 18-70
6	Women of child-bearing potential (defined as all women physiologically capa-ble of becoming pregnant) and all male participants must agree to use highly effective methods of contraception for one year following CD19.CAR T cell therapy
7	Ability to understand the nature of the trial and the trial related procedures
8	Written informed consent must be obtained prior to any screening procedures

2.1.2.8 Principal exclusion criteria

Exclusion criteria number	Principal exclusion criteria (English)
1	Immunosuppressive medication like a biological DMARD within 3 months, conventional synthetic DMARDs within 6 weeks or JAKi within 1 month be-fore leukapheresis with the exception of: - ≤ 30 mg prednisolone/d or equivalent at the time of leukapheresis and CAR T cell transfusion - Bridging/maintenance Mycophenolic acid/ Nintedanib. It must be stopped two weeks prior to leukapheresis, but can be continued be-tween leukapheresis and lymphodepletion, is stopped one week be-fore lymphodepletion and restarted at the earliest 4 weeks after CD19.CAR T cell therapy when suitable according to the treating phy-sician
10	Pregnant or nursing (lactating) women
11	Intolerance to the excipients of the cell product
12	Participation in another clinical trial at the time of screening
13	Insufficient command of the German language
2	Antigen- or DNA/RNA positive hepatitis B or C
3	HIV-positivity
4	Uncontrolled acute life-threatening bacterial, viral or fungal infection at the time of inclusion into the study
5	Severe concomitant disease (e.g. uncontrolled arterial hypertension, left heart failure NYHA III-IV, uncontrolled diabetes mellitus)
6	Unstable angina and/or myocardial infarction within 3 months prior to screen-ing
7	GFR < 30 mL/min/1.73 m2
8	Any previous or concurrent malignancy with the exception of non-melanoma skin cancer, in situ carcinoma of the cervix or breast, prostate cancer up to Gleason score 6 treated curatively without evidence of recurrence ≥ 3 years prior to the study, or a primary malignancy which is in complete remission for ≥ 5 years
9	Patients with active CNS involvement of their autoimmune disease must not be included in the study

2.1.2.9 Primary end points

End point criteria number

Primary end point (English)

1

Feasibility is defined to comply with a) successful manufacturing (definition see protocol section 3.4) as well as b) application of a CAR.T-cell product and c) tolerability of the procedure (no grade >3 CRS and no grade > 3 ICANS until V11). The primary endpoint is fulfilled if all prerequisites a)-c) are reached in at least 5/6 patients of the total feasibility cohort (3+3 – see protocol “sample size calculation” above) at V11.

2.1.2.10 Secondary end points

Secondary end point number	Secondary end point (English)
1	toxicities measured according to the Common Terminology Criteria for Adverse Events (CTCAE v6.0) or — in case of CRS or ICANS — according to ASTCT grad-ing
2	Clinical response is defined by improvement in pulmonary function. Improvement is defined as an increase of FVC by >10% plus an at least stable CO-diffusion capaci-ty, defined as no further decrease of more than - 5% from V3 numbers of TLCO/VA and TLCO SB until EOS (V15 of last patient in

2.1.2.11 Individual Participant Data (IPD) Sharing statement

Plan to share IPD:

No

Plan description:

2.1.2.12 Participants

Gender:

Male and Female

Age range:

65+ years, 18-64 years

Age range secondary identifier:

Clinical trial group:

Patients

Vulnerable population:

Yes

2.1.3.1 Study design

Period details:

Number	Period title	Period description	Allocation method	Blinding used	Roles blinded	Blinding implementation details	Arm details

2.2.1.1 Product: CD19.CAR T cells

Type

Product

Excluded MSCs

2.2.1.1.1 Product details

Medicinal product name:

CD19.CAR T cells

EU medicinal product number/medicinal product unique ID:

PRD11531000

Pharmaceutical form:

SOLUTION FOR INFUSION

Strength:

Medicinal product other name:

Is this a specific paediatric formulation:

No

Product authorisation status:

Not Authorised

Medicinal product role in trial:

Test

Sponsors product code:

CD19.CAR T cells

2.2.1.1.2 Products characteristics

Medicinal product characteristics:

Immunological, Containing GMO(s)

Other medicinal product:

2.2.1.1.3 Dosage and administration Details

Route of administration:

INTRAVENIOUS INFUSION

Maximum duration of treatment:

1 Day(s)

Maximum daily dose allowed:

200000000

Daily dose unit of measure:

Other

Maximum total dose allowed:

200000000

Total dose unit of measure:

Other

2.2.1.1.4 Information about the modification of the medicinal product

Has the medicinal product been modified in relation to its Marketing Authorisation:

No

Description of the modification:

2.2.1.1.5 Product classification

Anatomical Therapeutic Chemical (ATC) Codes:

ATC name:

ATC level:

2.2.1.1.6 Product authorisation details

MA holder

UNIVERSITY OF HEIDELBERG, MEDICAL FACULTY REPRESENTED BY HEIDELBERG UNIVERSITY HOSPITAL

MA authorisation country

Marketing authorisation number

Centralised procedure/MRP/DCP/registration procedure number

2.2.1.1.7 Orphan designation

Does this product have an orphan drug designation:

No

Designation number for orphan drug:

2.2.1.1.8 Active substance

Classification:

Structurally Diverse Substance - Cell therapy

Active Substance name:

T LYMPHOCYTES TRANSDUCED WITH A RV-SFG.CD19.CD28.4-1BBZETA RETROVIRAL VECTOR

Active substance name synonyms:

HD-CAR-1

Active Substance other descriptive name:

EU Active Substance Code:

SUB214535

Strength:

Status:

Not Authorised

2.2.1.1.9 Advanced therapy medicinal product

2.2.1.1.9.1 Gene Therapy

Advanced therapy classification

Gene Therapy

CAT reference number

Gene therapy medicinal product description

Gene of interest

Type of gene transfer product

Other

Gene therapy type

In Vivo

Additional description

Genetically modified cells

Genetically modified cells present?

Yes

Specify type of cells

Origin of the genetically modified cells

Xenogeneic

Species origin for the xenogenic cells

2.2.1.1.10 Device associated with medicinal product

Product used in combination with a device	Product ID	Device trade name	Description of the device	Type of device	Device has CE mark	Device notified body

2.2.1.1 Compliance with (GMP) for the medicinal product

Authorisation number of manufacturing and import: