A long term clinical study to determine the effect of albiglutide, when added to standard blood glucose lowering therapies, on major cardiovascular events in patients with Type 2 diabetes

• Register: EUCTR
• Last refreshed on: 30 April 2018
• Main ID: EUCTR2014-001824-32-NL
• Date of registration: 16/02/2015
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development Limited
• Public title: A long term clinical study to determine the effect of albiglutide, when added to standard blood glucose lowering therapies, on major cardiovascular events in patients with Type 2 diabetes
• Scientific title: A long term, randomised, double blind, placebo-controlled study to determine the effect of albiglutide, when added to standard blood glucose lowering therapies, on major cardiovascular events in patients with Type 2 diabetes mellitus - Harmony Outcomes
• Date of first enrolment: 13/04/2015
• Target sample size: 9400
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001824-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Czech Republic, Denmark, France, Germany, Greece, Hong Kong, Hungary, Italy, Korea, Republic of, Mexico, Netherlands, Norway, Peru, Philippines, Poland, Puerto Rico, Russian Federation, South Africa, Spain, Sweden, Taiwan, Thailand, Ukraine, United Kingdom, United States

Contacts

• Name: Alexandra H West
• Affiliation: GlaxoSmithKline Research & Development Limited

• Name: Alexandra H West
• Affiliation: GlaxoSmithKline Research & Development Limited

Key inclusion & exclusion criteria

Inclusion criteria:
1. Men or women at least 40 years old with a diagnosis of type 2 diabetes.
2. Established cardiovascular disease, including at least 1 of the following:
a.Coronary artery disease with EITHER of the following:
•Documented history of spontaneous myocardial infarction, at least 30 days prior to screening.
•Documented coronary artery disease (CAD) = 50% stenosis in 1 or more major epicardial coronary arteries, determined by invasive angiography, or history of surgical or percutaneous (balloon and/or stent) coronary revascularization procedure (at least 30 days prior to screening for percutaneous procedures and at least 5 years prior to study entry for coronary artery bypass graft (CABG)).
b.Cerebrovascular disease – ANY of the following:
•Documented history of ischaemic stroke, at least 90 days prior to study entry.
•Carotid arterial disease with = 50% stenosis documented by carotid ultrasound, magnetic resonance imaging or angiography, with or without symptoms of neurologic deficit.
•Carotid vascular procedure (e.g. stenting or surgical revascularisation), at least 30 days prior to screening.
c.Peripheral arterial disease (PAD) with EITHER of the following:
•intermittent claudication and ankle:brachial index < 0.9 in at least one ankle
•prior non-traumatic amputation, or peripheral vascular procedure (e.g. stenting or surgical revascularisation), due to peripheral arterial ischaemia.
3. HbA1c >7.0% (53 mmol/mol) based on the most recent documented laboratory assessment measured no more than 6 months prior to randomization. Local laboratory HbA1c values taken as part of usual care are permitted.
4. Female: subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin (hCG) test for females of reproductive potential only), not breastfeeding, and at least one of the following conditions applies:
a. Reproductive potential and agrees to follow one of the options listed in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) (e.g, combined oral contraceptive pill; see Appendix 2) from 30 days prior to the first dose of study medication and until
after the last dose of study medication and completion of the follow-up visit. This does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent. Other situations in which contraception in FRP may not need to be mandated should be discussed with the Medical Monitor.
b. Non-reproductive potential defined as either:
? Pre-menopausal with one of the following: (i) documented tubal ligation; (ii) documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; (iii) hysterectomy; or (iv) documented bilateral oophorectomy, or; Postmenopausal defined as 12 months of spontaneous amenorrhea and age appropriate (i.e. >50 years). In questionable cases, a blood sample with simultaneous follicle stimulating hormone (FSH) >40 mIU/mL and oestradiol <40 pg/mL (<140 pmol/L) is confirmatory, depending on local laboratory ranges. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status prior to study enrolment.
5
Exclusion criteria:
1. eGFR calculated using MDRD formula <30mL/min/1.73m2 (based on the most recent documented serum creatinine laboratory assessment measured no more than 6 months prior to randomization. Local laboratory creatinine values taken as part of usual care are permitted.) or renal replacement therapy.
2.Use of a GLP-1 receptor agonist at Screening.
3.Severe gastroparesis requiring therapy within 6 months prior to Screening.
4.History of pancreatitis or considered clinically at significant risk of developing pancreatitis during the course of the study (e.g. due to symptomatic gallstones, excess alcohol use).
5.Personal or family history of medullary carcinoma of the thyroid or subject with MEN-2. Personal history of pancreatic neuroendocrine tumours. In the opinion of the investigator, the subject has a medical history which might affect his / her ability to remain in the study for its entire duration, or which might limit management, such as life expectancy of <5 years (e.g. due to active malignancy).
6.Subject has a medical history which in the opinion of the investigator might limit the individual’s ability to take trial treatments for the duration of the study or to otherwise complete the study.
7.Breastfeeding, pregnancy, or planning a pregnancy during the course of the study. Pregnancy test will be required in women of child bearing potential. Women who have undergone a sterilisation procedure or who are clearly post-menopausal will not be required to undergo pregnancy testing. Women who have developed spontaneous secondary amenorrhoea of 12 months or more where post-menopausal status is in doubt, a blood sample where FSH >40MU/ml and oestrodiol <40 pg/mL (<140 pmol/L) are simultaneously measured will be considered confirmatory.
8.Known allergy to any GLP-1 receptor agonist or excipients of albiglutide.
9.Use of another investigational product within 30 days or according to local regulations, or currently enrolled in a study of an investigational device.
10.Any other reason the investigator deems the subject to be unsuitable for the study.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Diabetes mellitus type 2
MedDRA version: 20.0 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000072461

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Trade Name: Eperzan
Product Name: albiglutide
Product Code: GSK716155
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: albiglutide
CAS Number: 782500-75-8
Current Sponsor code: GSK716155
Other descriptive name: ALBIGLUTIDE
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 30-50
Pharmaceutical form of the placebo: Powder and solvent for solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: 1. To supplement the primary objective by further characterization of the effects of albiglutide on cardiovascular outcomes.
2. To evaluate the effects of albiglutide on metabolic management of type 2 diabetes.
3. To evaluate the safety of albiglutide.

Timepoint(s) of evaluation of this end point: The study will be event driven, i.e. follow up will continue until it is projected that approximately 611 adjudicated MACE events will have occurred. Consequently, the maximum duration of the study for an individual participant is dependent both on the time taken for recruitment and the MACE event rate, and is estimated to be between 3 and 5 years.

Main Objective: To determine whether albiglutide is non-inferior with respect to MACE when added to glycaemic standard of care versus standard of care alone.

Primary end point(s): Time to first occurrence of MACE (cardiovascular death, myocardial infarction, or stroke) [Non-inferiority]

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: The study will be event driven, i.e. follow up will continue until it is projected that approximately 611 adjudicated MACE events will have occurred. Consequently, the maximum duration of the study for an individual participant is dependent both on the time taken for recruitment and the MACE event rate, and is estimated to be between 3 and 5 years.

Secondary end point(s): 1. Time to first occurrence of MACE [Superiority]
•Time to first occurrence of the following:
-MACE or urgent revascularisation for unstable angina
-The individual components of the primary endpoint
-Cardiovascular death or hospitalization due to heart failure

2. Time to initiation of insulin of more than 3 months duration for those subjects not treated with insulin at study start.
•Time to initiation of prandial insulin in those subjects on basal insulin at study start
•The proportion of subjects achieving glycaemic control (HbA1c = 7.0% at final assessment) with no severe hypoglycaemic incidents and weight gain <5% of body weight.
•The time to first occurrence of a clinically important microvascular event (see Section 6.2.4 of the protocol)
•Change in HbA1c
•Change in body weight
•Patient reported outcomes from TRIM-D/EQ5D

3.
•All cause mortality
•Non-fatal SAEs
•AEs leading to discontinuation of investigational product
•AE of special interest (see Section 6.2.3 of the protocol)
•Change in eGFR calculated using Modification of Diet in Renal Disease (MDRD) formula
•Change in blood pressure and heart rate

Secondary ID(s)

116174

2014-001824-32-IT

Source(s) of Monetary Support

GlaxoSmithKline Research & Development Limited