AZD1656 in Transplantation With Diabetes tO PromoTe Immune TOleraNce

NCT ID: NCT05216172

Last Updated: 2024-06-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-13
• Study Completion Date: 2022-09-11

Brief Summary

AZD1656 in Transplantation with Diabetes tO PromoTe Immune TOleraNce: a single site, placebo-controlled, double-blind randomised clinical trial of AZD1656 in renal transplant patients with Type 2 diabetes

Detailed Description

Transplant recipients with pre-existing Type 2 diabetes frequently experience a deterioration in glycaemic control in the early post-transplant period, largely due to the significant immunosuppression burden at this stage. Elevated glucose profiles have been associated with poorer graft outcomes. The glucokinase activator AZD1656 has been shown to be a potent anti diabetic medication and safe in patients with T2DM, including those with chronic kidney disease. Recent data has shown that glucokinase activation increases regulatory T cell (Treg) migration and trafficking. The investigators propose to study the safety and efficacy of AZD1656 in optimising the glycaemic control and in stimulating Treg migration to the transplant kidney in a population of renal transplant patients with pre-existing T2DM.

ADOPTION is a single site, placebo-controlled, double-blind randomised clinical trial of AZD1656 in patients with Type 2 diabetes who have received a new renal transplant. Eligible, consented patients are randomised to a 3 month course of either active drug or placebo within 24 hours of transplantation. Clinical and laboratory data will be collected and assessed at baseline and throughout their participation in the study. The study plans to enrol 50 patients. There are no interim analyses planned. The primary endpoint will be the mean change in peripheral Tregs between baseline and 3 months as analysed by flow cytometry.

Ethical approval was obtained from the East of England - Cambridge East Ethics Committee (REC 19/EE/0209) prior to commencing the study. All study-related data will be used by the Sponsor in accordance with local data protection law. Results of the trial will be submitted for publication in a peer-reviewed journal.

Conditions

Type 2 Diabetes; Diabetes Mellitus, Type 2; Renal Transplant; Kidney Transplant; Complications; End Stage Renal Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

AZD1656

AZD1656 100mg BD for 3 months

Group Type: EXPERIMENTAL

AZD1656

Intervention Type: DRUG

active drug

placebo

placebo 100mg BD for 3 months

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo

Interventions

AZD1656

active drug

Intervention Type: DRUG

Placebo

placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Females or males aged 18 years and above

2. Having undergone renal transplantation at the Royal London Hospital within the previous 24 hours

3. A pre-transplant diagnosis of Type 2 diabetes

4. Provision of written, informed consent prior to any study specific procedures

5. In women of childbearing potential* documentation of a negative pregnancy test during admission for renal transplant.

• Women of childbearing potential are defined as women following menarche until becoming post-menopausal, unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A post-menopausal state is defined as the absence of menses for 12 months without an alternative medical cause.

Exclusion Criteria

1. Unable to consent

2. Known allergy/intolerance to AZD1656

3. Pregnant or breastfeeding women

4. Planning on becoming pregnant/unwilling to use highly effective contraception* during the 3 month treatment period and for 2 weeks afterwards (i) In the case of men with sexual partners who are women of childbearing potential: refusal to wear a condom and female partner planning on becoming pregnant/unwilling to use highly effective contraception* during the 3 month treatment period and for 2 weeks afterwards

5. Clinically significant history of abnormal physical and/or mental health as judged by the investigator other than conditions related to chronic kidney disease

6. Current or planned use of strong inhibitors of CYP2C8

7. Participation in an investigational drug trial in the 3 months prior to administration of the initial dose of study drug

• Highly effective contraception methods are defined as those that can achieve a failure rate of <1% per year when used correctly and consistently. These include:

• Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation - either oral, transvaginal or transdermal
• Progestogen-only hormonal contraception associated with inhibition of ovulation - either oral, injectable or implantable
• Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Vasectomised partner - provided that the partner is the sole sexual partner of the participant and that the vasectomised partner has received medical assessment of surgical success

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Queen Mary University of London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kieran McCafferty, M.B., B.Chir

Role: PRINCIPAL_INVESTIGATOR

Barts Health NHS Trust; Queen Mary University London

Locations

Royal London Hospital Barts Health NHS Trust

London, , United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

252155

Identifier Type: -

Identifier Source: org_study_id