A study to investigate whether treatment with a siplizumab-based regimen can induce allogeneic tolerance in liver transplant recipients.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Itb-Med AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

29 Jun 2022 → ongoing

Decision date (initial)

2024-07-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

ITB-Med AB

External identifiers

EU CT number

2023-508397-29-00

EudraCT number

2021-001680-24

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Prophylaxis, Pharmacodynamic

To investigate whether a siplizumab-based regimen can induce allogeneic tolerance in deceased donor liver transplant recipients.

Secondary objectives 1

1. To explore the safety of siplizumab

Conditions and MedDRA coding

Prophylaxis against liver allograft rejection following tolerance induction

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Recipients are able to understand the study requirements and provide written informed consent before any study assessment performed.
2. Male or female aged 18-70 receiving an ABO compatible deceased donor liver transplant.
3. Model for end-stage liver disease (MELD) score <30 on recent evaluation within 60 days of screening
4. Stable cardio-pulmonary status per the judgement of the investigator and eligible for transplantation per local regulations.
5. Epstein-Barr virus (EBV) sero-positive.
6. Male subjects must agree to maintain barrier contraception (condom) and further agree not to father a child for at least 4 months after the last dose of cyclophosphamide and 3 months after the last dose of mycophenolate mofetil (MMF).
7. Women of childbearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must agree to use highly effective methods of contraception during dosing and for at least 12 months after the last dose of cyclophosphamide.

Exclusion criteria 12

1. Use of other investigational drugs (or enrollment in another investigational drug study) within 30 days of screening or 5 half-lives of the medication, whichever is longer
2. Subjects with any other clinically significant medical condition or laboratory abnormality that would, in the judgment of the investigator interfere with the subject's ability to participate in the study
3. Subjects who have received any live-attenuated vaccine within 2 months of planned transplant.
4. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test
5. History of hypersensitivity to any of the study treatments or their excipients or to drugs of similar chemical classes (e.g., siplizumab, tacrolimus (TAC), cyclophosphamide or MMF)
6. End stage liver disease of autoimmune origin, including autoimmune hepatitis, primary biliary cholangitis or primary sclerosing cholangitis.
7. Subjects with leukopenia (WBC ≤2,000/mm3) or thrombocytopenia (platelet count < 70,000/mm3) at baseline
8. Sero-positive for human immunodeficiency virus-1 (HIV-1) or hepatitis B surface antigen (HBsAg). Subjects who are sero-positive for Hepatitis C (HCV)virus are excluded without proof of sustained viral response (SVR) after anti-HCV treatment
9. Subjects with a history of tuberculosis (TB) or latent TB infection as detected by Quantiferon Gold Plus interferon-gamma release assay (IGRA) (or current standard interferon gamma release assay for TB)
10. Subjects with extrahepatic malignancy or history of same, other than basal cell carcinoma of the skin or carcinoma in situ of the cervix.
11. Cardiac ejection fraction ≤ 40% within 6 months or clinical evidence of cardiac insufficiency
12. Subjects who, in the opinion of the investigator, are not capable of giving informed consent for the study or who are unable or unwilling to adhere to the study requirement outlined in the protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of patients who are free from immunosuppression at Month 30 post-transplant.

Secondary endpoints 3

1. Composite efficacy failure rate of treated biopsy proven acute rejection (tBPAR), graft loss or death at Month 30
2. The proportion of patients who remain off immunosuppression for at least 12 months
3. Incidence, severity, and treatment of acute rejection (derived from the biopsy, rejection, adverse event (AE) and treatment Case Report Forms (CRFs))

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Itb-Med AB

Sponsor organisation

Itb-Med AB

Address

Hagaplan 4

City

Stockholm

Postcode

113 68

Country

Sweden

Scientific contact point

Organisation

Itb-Med AB

Contact name

Kellie Calderon

Public contact point

Organisation

Itb-Med AB

Contact name

Clinical Trial Information

Third parties 8

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

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

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