E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human immunodeficiency virus (HIV) Infection and Obesity |
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E.1.1.1 | Medical condition in easily understood language |
HIV Infection and Obesity |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020161 |
E.1.2 | Term | HIV infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029883 |
E.1.2 | Term | Obesity |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of GLP- 1 analogue therapy (subcutaneous semaglutide) as an adjunct to diet and exercise in achieving greater weight loss in people living with HIV and obesity (PLWHO) as compared to diet and exercise alone. |
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E.2.2 | Secondary objectives of the trial |
To explore the effect of GLP-1 analogue therapy on markers of inflammation, immune function and HIV viral reservoirs in PLWHO. To explore the effect of GLP-1 analogue therapy on markers of glucose and lipid metabolism in PLWHO. To explore the effect of GLP-1 analogue therapy on markers of gut microbial translocation in PLWHO. To assess the safety of semaglutide therapy in PLWHO on stable ART. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Be over 18 years old • Be HIV-1 antibody positive as determined by a positive 3rd or 4th generation Ag/Ab ELISA assay • Be on stable ART for at least 2 years, with the last two viral loads <40 copies/mL or equivalent, based on local testing protocols • Have a CD4 count ≥200 cells/mm3 for a minimum of 1 year • Have a BMI ≥30kg/m2 or have a BMI ≥27kg/m2 and hypertension, dyslipidaemia or type 2 diabetes mellitus • Understand the study procedures, be able to comply with the study procedures, and voluntarily agree to participate by giving written informed consent for the trial |
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E.4 | Principal exclusion criteria |
• Subjects unable to comply with the study protocol or unable to selfadminister subcutaneous semaglutide • History of obesity induced by other endocrine disorders: Cushing’s syndrome, primary and secondary hypogonadism, hypothalamic disorders, polycystic ovary syndrome, insulinoma • Subjects with a diagnosis of diabetes mellitus who either have proliferative retinopathy or maculopathy requiring treatment or have not undergone retinal screening within the previous 12 months. • History hypothyroidism that has recently been poorly-controlled, defined as a TSH <0.5 mU/L or >10 mU/L within the last 12 months • Treatment with GLP-1 receptor agonists (including liraglutide, semaglutide or exenatide), dipeptidyl peptidase-4 (DPP-4) inhibitors or insulin within the last 3 months (including saxagliptin, linagliptin, sitagliptin) • History of severe renal impairment, as defined by a baseline creatinine clearance <30ml/min • History of lipoatrophy or lipodystrophy, as per physician’s assessment • Individuals with severe hepatic impairment (Child Pugh score >9) • Subjects with active hepatitis B infection (defined as hepatitis B sAg positive) or hepatitis C (defined as hepatitis C Ab and RNA positive) coinfection • Any active illness (including AIDS-defining illness), which in the opinion of the investigator precludes participation in the study • History of cancer (apart from treated Kaposi’s Sarcoma) and/or receiving chemotherapy or radiotherapy • Active illicit intravenous drug use • Subjects concurrently enrolled in another clinical trial of an investigational medicinal product • The investigator may decide that a subject cannot proceed in the study if there are any relevant other abnormal results in the screening assessments • Subjects with any known or suspected hypersensitivity to semaglutide or any of the excipients of semaglutide • Subjects on another medicinal product prescribed primarily for weight loss e.g. orlistat • For female subjects: pregnancy or breastfeeding at screening, planning future pregnancies or unwilling to take measures to avoid pregnancy for the duration of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in total body weight at week 28. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Change from baseline in total and subcutaneous fat, as measured by DXA at week 28. Changes from baseline to week 28 in markers of B-cell function, T-cell function, innate immunity, inflammation, gut microbiome composition, adipose tissue function, cholesterol and glucose metabolism and HIV RNA and HIV viral reservoir. The proportion of subjects in both arms not achieving ≥ 5% weight loss from baseline at week 16. Proportion with reported AE/AR, SAE/SAR Change in health-related quality of life (QOL) at week 28. Change in PR interval (sec) on ECG from baseline to week 4 stratified by class of antiretrovirals
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 4, Week 16 and Week 28 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |