A phase I/II study of CAR-expressing Allogenic iPSC derived NK cells for treatment of autoiMmune disease by B cELl depletion - CARAMEL

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Erlangen AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

30 Jul 2025 → ongoing

Decision date (initial)

2025-05-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Century Therapeutics

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the safety of CNTY-101 in subjects with active B-cell driven autoimmune disease (SLE, SSC and IIM)

Secondary objectives 2

1. To assess the clinical efficacy of CNTY-101 in subjects with active B-driven autoimmune disease (SLE, SSc and IIM)
2. To evaluate incidence, severity and duration of Adverse Events

Conditions and MedDRA coding

Idiopathic inflammatory myositis

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Fulfilling the 2019 ACR/EULAR classification criteria of SLE
2. Positivity of anti-dsDNA (>4U/L), anti-histone (+ or more), anti-nucleosome (+ or more) or anti-Sm antibodies (+ or more) at screening or documented medical history
3. Active disease at screening, defined as ≥1 organ system with a British Isles Lupus Assessment (BILAG) A score (severe disease activity) or ≥2 organ systems with a BILAG B score (moderate disease activity)
4. Insufficient response or intolerance/contraindication to glucocorticoids and to at least 2 of the following treatments: azathioprine, mycophenolate mofetil, belimumab, methotrexate, rituximab, obinutuzumab, anifrolumab, cyclophosphamide; insufficient response is defined as having increased disease activity based on the definition explained in the previous bullet point
5. Fulfilling the 2013 ACR/EULAR classification criteria of SSc
6. Diffuse SSc with positivity (+ or more) of either Scl70, RNA polymerase, Th/To, RP11/12 or U3RNP autoantibodies at screening or documented medical history
7. Signs for fast progression including (i) disease duration ≤7 5 years (from onset of first non-Raynaud manifestation), (ii) mRSS score 10-35≥ 15 at screening, (iii) elevated acute phase reactant levels (CRP ≥6 mg/L, ESR ≥28 mm/h or platelet count ≥330 G/L), (iv) mRSS increase ≥3 units or involvement of one new body area or mRSS increase ≥2 units in one body area or ≥1 tendon friction rub over 6 months
8. Insufficient response or intolerance/contraindication to glucocorticoids and to at least 2 of the following treatments: mycophenolate mofetil, azathioprine, nintedanib, methotrexate, rituximab, cyclophosphamide, tocilizumab and not eligible or denying AHCT
9. Fulfilling the 2017 ACR/EULAR classification criteria for probable or definite IIM
10. Presence of active myositis in muscle biopsy or muscle imaging and/or signs of interstitial lung disease related to IIM
11. Positivity (+ or more) for at least one myositis-specific antibody (aminoacyl tRNA synthetases, Mi2, MDA5, SAE, SRP, ARS, HMGCR, MJ, TIF1gamma) at screening or documented medical history. Patients with positivity for TIF1gamma must have undergone a sufficient cancer screening prior screening.
12. In patients with active myositis and muscle weakness: Muscle weakness as defined by MMT<142 and 2 of the following criteria: i) VAS patients global ≥2cm; ii) VAS physician global ≥2cm; iii) HAQ >0.25; iv) minimum of one muscle enzyme >1.3 times upper limit of normal; v) VAS global extra muscular activity ≥2cm
13. Insufficient response or intolerance/contraindication to glucocorticoids and to at least 2 of the following treatments: mycophenolate mofetil, ciclosporin A, tacrolimus, methotrexate, rituximab, intravenous immunoglobulins, azathioprine, cyclophosphamide or JAKi; insufficient response is defined as having increased disease activity based on the definition explained in the previous bullet point

Exclusion criteria 14

1. Uncontrolled severe concomitant disease, such as cancer (except basal or squamous cell skin cancer), diabetes mellitus or severe hepatic insufficiency defined as Child Pugh score ≥ 10 (C) or unstable coronary artery disease
2. Severely impaired renal (GFR ≤30 ml/min/1.73m2), liver (AST/ALT >3xN, Child Pugh C), heart (NYHA IV, EF <40 %) and pulmonary (FV and DLCO <30 %) function
3. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
4. Prior treatment with anti-CD19 CAR-T cell therapy
5. History of allogeneic bone marrow/hematopoietic stem cell transplantation
6. Any concomitant severe active infection, e.g., HIV, hepatitis B or C, SARS-CoV 2 (COVID 19), or active tuberculosis as defined by a positive Quantiferon TB-test; if presence of latent tuberculosis is established then treatment according to local guidelines must have been initiated prior to enrollment
7. Diagnosis of severe neuropsychiatric SLE, inclusion body myositis or limited SSc
8. Pregnant or lactating females as well as the intention to conceive during the study
9. Known hypersensitivity to any drug components
10. Malignancy in the last 5 years before screening, except localized basal cell or squamous skin carcinoma, treated curatively and without evidence of recurrence. In situ carcinoma of the cervix or breast within the past 3 years is also allowed if treated curatively and without evidence of recurrence
11. Requirement for immunization with live vaccine during the study period or within 14 days preceding LDC
12. Subjects who are younger than 18 years or are incapable to understand the aim, importance and consequences of the study and to give legal informed consent
13. Have a history of alcohol or substance abuse within the preceding 6 months that, in the opinion of the Investigator, may increase the risks associated with study participation or study agent administration, or may interfere with interpretation of results
14. Subjects who possibly are dependent on the Sponsor, the Principal Investigator or Investigator (e.g., family members)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of any GvHD, any grade ≥ 3 CRS or grade ≥ 3 ICANS, any grade ≥ 3 organ toxicity that does not resolve to grade ≤ 2 within 72 hours, any grade ≥ 3 immune effector cell-associated hemophagocytosis, grade ≥ 2 ICANS and CRS that does not resolve to grade 1 within 7 days following adequate therapy.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Erlangen AöR

Sponsor organisation

Universitaetsklinikum Erlangen AöR

Address

Maximiliansplatz 2, Innenstadt Innenstadt

City

Erlangen

Postcode

91054

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Erlangen AöR

Contact name

Klinik für Rheumatologie und Immunologie

Public contact point

Organisation

Universitaetsklinikum Erlangen AöR

Contact name

Klinik für Rheumatologie und Immunologie

Locations

1 EU/EEA country · 1 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 5 files

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

Application history

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