A 3-month, phase 2, single-blind, randomised, no-treatment controlled study assessing efficacy and safety of Renaparin® for improvement of kidney graft function in deceased-donor transplant recipients, with an additional 9-month follow-up.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Corline Biomedical AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12], Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Decision date (initial)

2023-01-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the effect of Renaparin on graft function in renal transplant patients at high risk of ischemia-reperfusion injury (IRI) and delayed graft function (DGF) who have received a kidney – preserved in SCS – from a deceased donor that meets the criteria for DBD-ECD or DCD.

Secondary objectives 2

1. To assess safety and tolerability of Renaparin in renal transplant patients.
2. To assess Renaparin uptake on the kidney vascular endothelium in cold storage.

Conditions and MedDRA coding

end-stage renal disease or otherwise an insufficient kidney function

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Organs: A kidney must fulfil the following criteria in order to be used in the study: 1) Kidney must come from a deceased donor at least 18 years of age. 2) Kidneys donated after brain death (DBD-ECD) or kidneys donated after circulatory death (DCD).
2. Patients: A patient must fulfil the following criteria in order to be included in the study: 3) Male or female patient 18 – 75 years of age. 4) Dialysis-dependent (initiated more than two months prior to transplantation) patient, acceptable candidate for kidney transplantation. 5) Female patients must be post-menopausal, surgically sterile or using effective methods of contraception during study treatment (3 months). Acceptable birth control methods are those with a failure rate of less than 1% per year when used consistently and correctly. Such methods include: a) Combined (oestrogen and progestogen containing hormonal contraception associated with inhibition of ovulation -oral -intravaginal -transdermal b) progestogen-only hormonal contraception associated with inhibition of ovulation -oral -injectable -implantable c) intrauterine device d) intrauterine hormone-releasing system e) bilateral tubal occlusion f) vasectomized partner 6) Patient weight 45-115 kg. 7) Negative crossmatch test prior to transplantation and no evidence of donor-specific antibodies. 8) Patients able to give informed consent to participate in study.

Exclusion criteria 2

1. Organs: The presence of any of the following will exclude a kidney from being used in the study: 1) Kidney judged by the transplantation surgeon on call as not appropriate for transplantation. 2) Kidney allograft that was on HMP > 6 hrs prior to administration of IMP, or prior to transplantation for the control kidney. 3) Kidney judged to need preservation by HMP up until transplantation.
2. Patients: The presence of any of the following will exclude a patient from participating in the study: 4) Increased risk of thrombosis (e.g., homozygous activated protein C [APC]-resistance) or bleeding (INR>1.5). 5) History of heparin-induced thrombocytopenia (HIT). 6) Known fish allergy. 7) History of or positive for human immunodeficiency virus (HIV). 8) Acute infection with hepatitis B virus (HBV), or hepatitis C virus (HCV). 9) History of oncological malignancy within the last five years, except excised squamous or basal cell carcinoma of the skin. 10) Previous kidney transplantation. 11) Scheduled to undergo multi-organ transplantation or dual kidney transplantation. 12) Positive T or B cell crossmatch by NIH anti-globulin lymphocytotoxicity method or positive T or B cell flow cytometry crossmatch AND donor specific anti-HLA antibody (DSA) detected by flow cytometry/Luminex based, antigen specific anti-HLA antibody testing, according to local practise. 13) Current drug and/or alcohol abuse. 14) History or presence of a medical condition or disease or psychiatric condition that in the investigator's assessment would place the patient at an unacceptable risk for study participation. 15) Lactating or pregnant women or women who intend to become pregnant. 16) Presence of ECG-based evidence of acute myocardial infarction, unstable angina, decompensated heart failure, third degree of heart block or cardiac arrhythmia associated with haemodynamic stability. 17) Any medical condition which in the opinion of the investigator makes the patient unsuitable for inclusion. 18) Enrolment in another concurrent clinical interventional study, or intake of an IMP, within 3 months prior to inclusion in this study. 19) Foreseeable inability to cooperate with given instructions or study procedures. 20) Patients receiving prophylactic treatment of lymphocyte-depleting agents (e.g., anti-thymocyte globulin [ATG] or Campath).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the estimated glomerular filtration rate (eGFR) at Month 3, calculated using the MDRD 4 equation.

Secondary endpoints 10

1. Incidence of DGF (need for dialysis during first 7 days post-transplantation).
2. Serum creatinine on Days 1-7, Day 30, and Months 3, 6, and 12.
3. eGFR on Days 1-7, Day 30, Month 6 and Month 12.
4. Severity of DGF, i.e., total number of dialysis sessions received by a patient through Day 30 in patients requiring dialysis within first 7 days post-transplantation.
5. Incidence of functional DGF (fDGF), i.e., failure of serum creatinine to decrease by at least 10% daily on 3 consecutive days during the first 7 days post-transplantation, irrespective of dialysis requirements, but discounting creatinine decrements because of dialysis itself.
6. DGF duration (days); calculated from the date of kidney transplantation until the date of last dialysis session in patients who required at least one dialysis session within the first 7 days post-transplantation.
7. The proportion of patients with immediate graft function (IGF), i.e., patients with creatinine reduction ratio (CRR) ≥30% between Day 1 and Day 2 post-transplant, irrespective of whether or not they had a single dialysis session within the first 7 days post-transplant.
8. Proportion of patients with primary non-function (PNF), i.e., those who receive an allograft that never functions.
9. The time to first dialysis (days) excluding patients with PNF.
10. Urine output on Days 1-3.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Corline Biomedical AB

Sponsor organisation

Corline Biomedical AB

Address

Lefflersgatan 5, Vaksala Vaksala

City

Uppsala

Postcode

754 50

Country

Sweden

Scientific contact point

Organisation

Corline Biomedical AB

Contact name

Patrizia Caldirola

Public contact point

Organisation

Corline Biomedical AB

Contact name

Henrik Nittmar

Third parties 1

Locations

2 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Application history

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