A randomised, controlled, parallel group, open-label trial evaluating the impact of treatment with the GLP-1 analogue semaglutide on weight loss in people living with HIV and obesity (SWIFT Study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University College Dublin

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02], Phenomena and Processes [G] - Metabolism [G03]

Trial duration

1 Jun 2022 → ongoing

Decision date (initial)

2025-06-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-513168-24-00

EudraCT number

2019-002314-39

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

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.

Secondary objectives 4

1. To explore the effect of GLP-1 analogue therapy on markers of inflammation, immune function and HIV viral reservoirs in PLWHO.
2. To explore the effect of GLP-1 analogue therapy on markers of glucose and lipid metabolism in PLWHO.
3. To explore the effect of GLP-1 analogue therapy on markers of gut microbial translocation in PLWHO.
4. To assess the safety of semaglutide therapy in PLWHO on stable ART.

Conditions and MedDRA coding

HIV & Obesity

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Be over 18 years old
2. Be HIV-1 antibody positive as determined by a positive 3rd or 4th generation Ag/Ab ELISA assay
3. 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
4. Have a CD4 count ≥200 cells/mm3 for a minimum of 1 year
5. Have a BMI ≥30kg/m2 or have a BMI ≥27kg/m2 and hypertension, dyslipidaemia or type 2 diabetes mellitus (see Appendix G – Diagnostic Criteria)
6. 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

Exclusion criteria 18

1. Subjects unable to comply with the study protocol or unable to selfadminister subcutaneous semaglutide
2. Any active illness (including AIDS-defining illness), which in the opinion of the investigator precludes participation in the study
3. History of cancer (apart from treated Kaposi’s Sarcoma) and/or receiving chemotherapy or radiotherapy
4. Active illicit intravenous drug use
5. Subjects concurrently enrolled in another clinical trial of an investigational medicinal product
6. The investigator may decide that a subject cannot proceed in the study if there are any relevant other abnormal results in the screening assessments
7. Subjects with any known or suspected hypersensitivity to semaglutide or any of the excipients of semaglutide
8. Subjects on another medicinal product prescribed primarily for weight loss e.g. orlistat (see Section 5.2.2 Prohibited/Cautioned Concomitant Medications/Therapies)
9. 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.
10. History of obesity induced by other endocrine disorders: Cushing’s syndrome, primary and secondary hypogonadism, hypothalamic disorders, polycystic ovary syndrome, insulinoma
11. 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.
12. 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
13. 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)
14. History of severe renal impairment, as defined by a baseline creatinine clearance <30ml/min
15. History of lipoatrophy or lipodystrophy, as per physician’s assessment
16. Individuals with severe hepatic impairment (Child Pugh score >9)
17. Subjects with active hepatitis B infection (defined as hepatitis B sAg positive) or hepatitis C (defined as hepatitis C Ab and RNA positive) coinfection
18. Personal or family history of medullary thyroid carcinoma (MTC) or in individuals with Multiple Endocrine Neoplasia (MEN)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in total body weight at week 28.

Secondary endpoints 6

1. Change from baseline in total and subcutaneous fat, as measured by DXA at week 28.
2. 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.
3. The proportion of subjects in both arms not achieving ≥ 5% weight loss from baseline at week 16.
4. Proportion with reported AE/AR, SAE/SAR
5. Change in health-related quality of life (QOL) at week 28.
6. Change in PR interval (sec) on ECG from baseline to week 4 stratified by class of antiretrovirals

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University College Dublin

Sponsor organisation

University College Dublin

Address

Catherine Mcauley Centre, 21 Nelson Street, Phibsborough 21 Nelson Street Phibsborough

City

Dublin 7

Postcode

DUB LIN7

Country

Ireland

Scientific contact point

Organisation

University College Dublin

Contact name

Paddy Mallon

Public contact point

Organisation

University College Dublin

Contact name

Gráinne O'Reilly

Third parties 1

Locations

3 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 24 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications