A 12-Month Clinical Research Study to evaluate a new investigational medication (siplizumab) compared to another medication (anti thymocyte globulin) for the prevention of rejection in patients who have received a kidney transplant.

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

6 Jun 2021 → 12 Dec 2024

Decision date (initial)

2024-02-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

ITB-Med AB

External identifiers

EU CT number

2023-507895-36-00

EudraCT number

2020-000419-56

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Pharmacodynamic, Efficacy, Pharmacokinetic, Safety, Dose response

To assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of siplizumab compared to rabbit anti-thymocyte globulin (rATG), in de novo renal transplant recipients over 12 months post-transplant.

Secondary objectives 7

1. To measure changes in peripheral lymphocyte immunophenotype.
2. To measure the time-course and duration of siplizumab induced lymphocyte depletion and time to recovery.
3. To measure peripheral CD2-RO following siplizumab administration over time.
4. To assess the incidence of treated biopsy proven acute rejection (tBPAR) over 12 months.
5. To assess the incidence of treatment emergent de novo, donor specific antibodies (DSA) over 12 months.
6. To assess the incidence of antibody meditated rejection over 12 months.
7. To assess renal function via eGFR using MDRD equation at Months 3, 6, and 12 (End of Study [EOS]/Early Termination [ET])

Conditions and MedDRA coding

Renal Transplantation

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Able to understand the study requirements and provide written informed consent before any study assessment is performed.
2. Male or female patients ≥ 18 to 70 years of age.
3. Recipients of a de novo renal allograft from a heart-beating deceased, living unrelated or non-human leukocyte antigen (HLA) identical living related donor.
4. Recipients of a kidney with a cold ischemia time (CIT) < 30 hours; hypothermic machine perfusion within the same timeframe is acceptable.

Exclusion criteria 23

1. Transplant recipients seronegative for Epstein-Barr virus (EBV).
2. Multi-organ transplant recipients.
3. Subjects who have received a kidney allograft previously (e.g. re-transplant).
4. Recipient of a kidney from an HLA identical living related donor
5. Recipient of a kidney from a donor after cardiac death
6. Subjects at high immunological risk for rejection as determined by local practice (e.g., presence of pre-existing donor-specific antibodies [DSA], recipient of high Kidney Donor Profile Index ≥ 85 kidney (where assessed).
7. Subjects with anti-HLA donor specific antibody as measured by complement-dependent cytotoxicity (CDC) assay, enzyme-linked immunosorbent assay (ELISA), or flow cytometry within 90 days prior to transplant or as performed per the center's local practice.
8. Complement-dependent cytotoxicity (CDC) crossmatch positive transplant (isolated positive B cell crossmatches are not an exclusion criterion).
9. ABO incompatible recipient
10. History of malignancy of any organ system, except for localized excised non-melanomatous skin lesions or carcinoma in situ of the cervix.
11. Subjects with clinically significant laboratory abnormality that would preclude participation in the study. For example: >2.5 × upper limit of normal (ULN) values for: - Liver function chemistries (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP]) - Bilirubin - Coagulation studies (International Normalized Ratio [INR]/prothrombin time [PT], activated partial thromboplastin time [aPTT]).
12. Subjects with any of the following: • Hemoglobin (Hgb) < 8 mg/dL • White blood cell (WBC) count ≤ 2,000/mm3 • Platelet count ≤ 75,000/mm3.
13. Seropositive for human immunodeficiency virus (HIV) or hepatitis B surface antigen (HBsAg). Subjects who are seropositive for hepatitis C virus (HCV) are excluded without proof of sustained viral response (SVR) after anti-HCV treatment.
14. Recipient of a kidney from a donor who tests positive for HIV, HBsAg/hepatitis B core antigen (HBcAg) positive or HCV.
15. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes (e.g., siplizumab, anti-thymocyte globulin [ATG], tacrolimus [TAC], mycophenolate mofetil [MMF], corticosteroifs [CS]).
16. Any additional contraindication to the use of TAC or MMF according to the national labeling information of these products (refer to the local product label).
17. Evidence of tuberculosis (TB) infection (after anti-TB treatment, patients with history of latent TB may become eligible according to national guidelines).
18. Subjects with severe systemic infections, current or within the two weeks prior to randomization.
19. Subjects with any other clinically significant medical condition, active infection or laboratory abnormality that would, in the judgment of the Investigator, interfere with the subject’s ability to participate in the study.
20. 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 requirements outlined in the protocol.
21. Use of other investigational products or enrollment in another investigational drug study within 30 days of screening or 5 half-lives of the medication, whichever is longer.
22. 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.
23. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 24 weeks after the study medications have been stopped. Highly effective contraception methods include: Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential. Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject. Any of the following: Use of oral, injected, or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%); for example, hormone vaginal ring or transdermal hormone contraception. Placement of long-acting reversible contraceptives, an intrauterine device, or intrauterine system. In case of use of oral contraception, women should have been stable on the same brand (or generic equivalent) for a minimum of 3 months before taking study treatment. Additionally, total abstinence, when in line with the preferred and usual lifestyle of the subject, may be an acceptable form of contraception. Withdrawal and period abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) are not acceptable forms of contraception. Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment if she is considered not of childbearing potential.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 8

1. Adverse events (AEs)
2. Serious adverse events (SAEs)
3. Clinically significant changes in clinical chemistry, hematology, vital signs, serology
4. Siplizumab PK
5. Immunophenotyping
6. CD2 receptor occupancy (RO)
7. Estimated glomerular filtration rate (eGFR) via Modification of Diet in Renal Disease (MDRD) equation.
8. Anti-siplizumab antibodies

Secondary endpoints 7

1. Immunophenotyping via fluorescence-activated cell sorting (FACS).
2. Lymphocyte counts
3. CD2 RO
4. Incidence of tBPAR
5. de novo-DSA / anti-human leukocyte antigen (HLA) antibody measurement
6. Incidence of AMR
7. eGFR

Investigational products

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

Test 1

Comparator 3

Auxiliary 5

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

Alan Slade

Public contact point

Organisation

Itb-Med AB

Contact name

Clinical Trial Information

Third parties 7

Locations

3 EU/EEA countries · 7 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 14 files

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

Application history

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