A Research Study to Compare a Medicine Called Semaglutide Against Placebo in People With Peripheral Arterial Disease and Type 2 Diabetes

Study Overview
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Brief Summary
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This study is done to see if semaglutide has an effect on walking ability compared with placebo (dummy medicine) in people with peripheral arterial disease (PAD) and type 2 diabetes. Participants will either get semaglutide or placebo (dummy) medicine - which treatment participants get is decided by chance. Semaglutide is a medicine for type 2 diabetes that can be prescribed by doctors in some countries. Participants will get the study medicine (semaglutide or placebo) in a pre-filled pen for injection. Participants must inject it once a week into the stomach area, thigh, or upper arm, at any time of the day. The study will last for about 59 weeks. Participants will have 8 clinic visits and 1 phone call with the study doctor. At some clinic visits, participants will have blood tests. At some visits participants will also do a treadmill test to measure how far they can walk. Women cannot take part if pregnant, breast-feeding or planning to become pregnant during the study period.

Official Title
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Effects of Semaglutide on Functional Capacity in Patients With Type 2 Diabetes and Peripheral Arterial Disease

Conditions
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Diabetes Mellitus, Type 2, Peripheral Arterial Disease

Intervention / Treatment
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* Drug: Semaglutide
* Drug: Placebo (semaglutide)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age above or equal to 18 years at the time of signing informed consent. For Japan: Male or female, age above or equal to 20 years at time of signing informed consent Diagnosed with type 2 diabetes mellitus at least 180 days prior to the day of screening. Symptomatic PAD with intermittent claudication corresponding to Fontaine stage IIa (Rutherford classification grade I, category 1 and 2) meeting all of the following: Stable symptoms of PAD with intermittent claudication in Fontaine stage IIa (able to walk without stopping more than 200 m/656 feet/2 blocks) for at least 90 days prior to the day of screening based on patient interview. Screening flat treadmill test (3.2 km/h (2 mph)): Pain-free walking distance of at least 200 meters/656 feet. Screening constant load treadmill test with fixed inclination of 12% and a fixed speed of 3.2 km/h (2 mph): Walking distance equal to or less than 600 meters/1968 feet. Ankle-brachial-index (ABI) equal to or below 0.90 or toe-brachial index (TBI) equal to or below 0.7 (the leg with lowest index is chosen in case of bilateral disease). Exclusion Criteria: Current or previous treatment with any GLP-1 receptor agonist (GLP-1-RA) within 90 days prior to the day of screening. Walking ability limited by conditions other than PAD (e.g. aortic aneurism, dysregulated arrhythmia or hypertension, angina pectoris, heart failure, chronic obstructive or restrictive pulmonary disease, Parkinson's disease, severe peripheral neuropathy, amputations, wheel chair or walker dependency, osteoarthritis, morbid obesity, severe varicose veins, etc.). Planned orthopaedic surgery in the legs, or other major surgery known on the day of screening (surgery affecting walking ability). Vascular revascularisation procedure of any kind 180 days prior to the day of screening. Planned arterial revascularisation known on the day of screening. Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischemic attack within 180 days prior to the day of screening. Heart failure presently classified as being in New York Heart Association (NYHA) class III-IV.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide<br>Semaglutide given in addition to standard-of-care treatment | Drug: Semaglutide<br>* Semaglutide is administered subcutaneously (s.c.; under the skin) once-weekly for 52 weeks in a dose escalating manner: 0.25 mg from week 1 to week 4, 0.5 mg from week 5 to week 8 and 1.0 mg from week 9 to week 52.<br>|
| Placebo Comparator: Placebo (semaglutide)<br>Placebo given in addition to standard-of-care treatment | Drug: Placebo (semaglutide)<br>* Placebo (semaglutide) is administered s.c. once-weekly for 52 weeks in a dose escalating manner: 0.25 mg from week 1 to week 4, 0.5 mg from week 5 to week 8 and 1.0 mg from week 9 to week 52.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in maximum walking distance on a constant load treadmill test | Ratio to baseline | From baseline (week 0) to end of treatment (week 52) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Follow-up change in maximum walking distance on a constant load treadmill test | Ratio to baseline | From baseline (week 0) to end of follow-up (week 57) | 
| Change in Vascular Quality of Life Questionnaire-6 (VascuQoL-6) score | Score on a scale. Vascular Quality of Life 6 (VascuQoL): A shorter version of the standardized, validated questionnaire, VascuQoL-25 which is used to evaluate vascular disease-specific health outcomes. VascuQol total score includes scores of Activity Domain, Symptom Domain, Pain Domain, Emotional Domain and Social Domain. Each item is rated as a 4 point response scale, with a score of 1 being the worst and a score of 4 the best possible. The total score is the sum of all 6 items scores. Each question relates to a separate domain, with a highest score of 4 which indicates best health outcome. The VascuQoL-6 is aimed specifically at PAD patients | From baseline (week 0) to end of treatment (week 52) | 
| Change in pain-free walking distance on a constant load treadmill test | Ratio to baseline | Change in pain-free walking distance on a constant load treadmill test | 
| Follow-up change in pain-free walking distance on a constant load treadmill test | Ratio to baseline | From baseline (week 0) to end of follow-up (week 57) | 
| Change in glycosylated haemoglobin (HbA1c) | Percentage point | From baseline (week 0) to end of treatment (week 52) | 
| Change in body weight | Kilogram | From baseline (week 0) to end of treatment (week 52) | 
| Change in systolic blood pressure | mmHg | From baseline (week 0) to end of treatment (week 52) | 
| Change in total cholesterol | Ratio to baseline | From baseline (week 0) to end of treatment (week 52) | 
| Change in Low-density lipoprotein (LDL)- cholesterol | Ratio to baseline | From baseline (week 0) to end of treatment (week 52) | 
| Change in High density lipoprotein (HDL)- cholesterol | Ratio to baseline | From baseline (week 0) to end of treatment (week 52) | 
| Change in triglycerides | Ratio to baseline | From baseline (week 0) to end of treatment (week 52) | 
| Change in ankle-brachial index (ABI) | Ratio | From screening (week -2) to end of treatment (week 52) | 
| Change in toe-brachial index (TBI) | Ratio | From screening (week -2) to end of treatment (week 52) | 
| Change in Walking Impairment Questionnaire (WIQ) global score | Percentage point | From baseline (week 0) to end of treatment (week 52) | 
| Change in Short Form 36 (SF-36) physical functioning domain | Score on a scale. Short form (SF)-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health, of which will be summarised into a physical health. The physical score ranges from 24-101(where higher scores indicate a better physical capability). The domain scores will then be transformed into norm-based scores. At least seven domains must have valid data in order to calculate the physical health. To calculate physical health, the physical domain must be one of these seven domains. These scores will be summarised by domains and component summary scores by treatment and visit. A positive change in score indicates an improvement since baseline | From baseline (week 0) to end of treatment (week 52) |