REducing Diabetic MacrovascUlar Complications DuE to Peripheral Arterial Disease- REDUCE-PAD

NCT ID: NCT05912218

Last Updated: 2024-11-21

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-02
• Study Completion Date: 2025-12-01

Brief Summary

This is a Phase IIa, multi-centre study conducted at 3 sites in Singapore (SGH and NUHS, KTPH). 70 patients with diabetes mellitus (DM) and peripheral arterial disease (PAD) will be randomised in a ratio 1:1 to receive normal saline control or MEDI6570 400mg by monthly subcutaneous injection for 9 months.

Detailed Description

This is a mechanistic, randomised, double-blind, controlled Phase IIa trial that investigates whether 9 months of treatment with MEDI6570 affects lower limb microvascular perfusion and atheroma inflammation and progression. Patients with both DM and PAD will receive monthly subcutaneous injections of 400mg MEDI6570 (in an injection volume of 4.0ml), or injection/volume-matched normal saline control (4.0ml) subcutaneously, every 4 weeks for 32 weeks (9 doses in total). Com

Approximately 70 participants will be randomly assigned to a study intervention, with an anticipated 35 participants being randomized to receive active study intervention, and 35 participants being randomized to receive normal saline control.

The primary objective of the study is to determine whether monthly subcutaneous injections of MEDI6570 for 9 months reduces lower limb atheroma plaque inflammation and improves lower limb microvascular perfusion, when compared to normal saline control.

The primary endpoint in REDUCE-PAD will be the between-group difference (intervention vs. normal saline control) in the change in PET and MRI scan parameters from baseline to 9 months. Efficacy, safety, PK, and immunogenicity of MEDI6570 will also be evaluated in this study.

Conditions

Diabetes Mellitus, Type 2; Peripheral Arterial Disease

Study Design

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

Study Groups

MEDI6570

Biological MEDI6570,subcutaneous injection

Group Type: EXPERIMENTAL

MEI6570

Intervention Type: BIOLOGICAL

Saline Control

Placebo

Saline Control,subcutaneous injection

Group Type: PLACEBO_COMPARATOR

MEI6570

Intervention Type: BIOLOGICAL

Saline Control

Interventions

MEI6570

Saline Control

Intervention Type: BIOLOGICAL

Other Intervention Names

Placebo

Eligibility Criteria

Inclusion Criteria

1. Participant must provide informed consent before any study specific activities are performed, must be able and willing to meet all requirements for randomisation, and must adhere to the schedules of activities.

2. Men must be ≥ 21 years of age at the time of signing the ICF. Women must be ≥ 40 years of age at the time of signing the ICF. For female participants, the participant must not be pregnant or lactating and must be of non-childbearing potential, confirmed at screening Visit 1 by one of the following:

1. Postmenopausal, defined as amenorrhea for ≥ 12 months following cessation of all exogenous hormonal treatments, and with luteinizing hormone and follicle stimulating hormone levels in the postmenopausal range.

2. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy. Tubal ligation is not considered as irreversible surgical sterilization.

3. Participant must have body mass index within the range 18 to 40 kg/m2 inclusive.

4. Participants must have moderate stable PAD (ABI < 0.7 and/or TBI < 0.5) with no prior history of lower limb revascularisation or ulcers.

5. On stable medical therapy for type 2 DM for at least 6 weeks prior to screening with no clinically significant dose change and/or new medications in the recent 6 weeks

6. All male participants should refrain from fathering a child or donating sperm during the study and for 190 days following the last dose. Non-sterilised male study participants should be advised to use a condom for all sexual intercourse with a female partner of childbearing potential from Day 1 through the end of the study follow-up period.

Exclusion Criteria

1. History of any clinically important disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.

2. Uncontrolled Type 1 or Type 2 diabetes defined as haemoglobin A1c (HbA1c) >10%.

3. Increased risk of bleeding

1. Patients with history or presence of any bleeding disorder.

2. Signs of ongoing bleeding at screening (e.g., identified macroscopic bleeding, low haemoglobin presumed to be caused by bleeding) or high risk for major bleeding in accordance with the Investigator's assessment.

3. . Need for chronic therapeutic anticoagulation therapy anticipated to be required throughout the course of the study (short-term treatment with prophylactic doses of heparin/low molecular weight heparin are allowed).

4. Known severe liver disease (e.g., ascites and/or clinical signs of coagulopathy).

4. History or presence of any of the following:

1. Cancer within 5 years before randomization, except for non-melanoma skin cancer.

2. Alcohol or substance abuse within 6 months before randomization, as judged by the investigator.

3. Known history of hypersensitivity reactions to other biologics, to human IgG preparations, or to any component of MEDI6570, or ongoing severe allergy as judged by the investigator.

4. Patients with active positive results on screening for serum hepatitis B surface antigen, hepatitis C antibody, or HIV.

5. Any clinically important abnormalities in clinical chemistry, haematology, coagulation parameters, as judged by the investigator, including but not limited to:

1. AST > 2.0 × ULN.

2. ALT > 2.0 × ULN.

3. TBL > 1.5 x ULN (unless due to Gilbert's syndrome).

4. Platelet count < 100,000 platelets/μl.

6. BP values at screening Visit 1:

1. Systolic BP < 90 mmHg or > 180 mmHg.

2. Diastolic BP > 100 mmHg.

3. Participants who are excluded based on elevated BP may be rescreened following adequate treatment.

7. Any clinically important abnormalities in clinical chemistry, haematology, coagulation parameters, or urinalysis results.

8. History of blood dyscrasia, haemostatic disorder, systemic bleeding, or prior trauma that places the subject at a higher risk of bleeding.

9. Receipt of any investigational device or therapy within 6 months or 5 half-lives before screening (whichever is longer). This criterion does NOT apply for inactive, non-replicating COVID-19 vaccines approved by Health Authorities or under emergency use authorization.

10. Planned participation in an additional investigational study of an intervention or biologic before the end of the follow-up period. Participation in observational studies or studies without investigational drugs or devices is allowed.

11. Participants who are legally institutionalised.

12. An employee or close relative of an employee of the sponsor,

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Singapore General Hospital

OTHER

Sponsor Role: collaborator

Khoo Teck Puat Hospital

OTHER

Sponsor Role: collaborator

National University Health System, Singapore

OTHER

Sponsor Role: collaborator

National Heart Centre Singapore

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Prof Derek J. Hausenloy

Singapore, Singapore, Singapore

Countries

Singapore

Other Identifiers

REDUCE-PAD 1

Identifier Type: -

Identifier Source: org_study_id