Evaluating efficacy and safety of switching a boosted protease inhibitor to fostemsavir in PLWH with limited therapeutic options (FOST Switch)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

NEAT ID Foundation

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

5 Jun 2024 → ongoing

Decision date (initial)

2024-01-25

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ViiV Healthcare UK Ltd.

External identifiers

EU CT number

2023-504192-25-00

ISRCTN

ISRCTN10901519

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others

To assess the proportion of patients with HIV viral load ≥ 50 copies/mL at week 48.

Secondary objectives 10

1. Rates of individuals with VL < 50 copies/mL at week 48
2. Rates of individuals with VL < 200 copies/ml at week 24
3. Rates of individuals with VL < 200 copies/ml at week 48
4. CD4 count, CD4:CD8 ratio, and Lymphocyte subsets at week 48.
5. To evaluate the potential for drug-drug interactions in those who switch from their cART to Fostemsavir based on the University of Liverpool Drug interaction website or other sources of drug interaction knowledge, including prescribed drugs, hormones, over the counter medications and recreational drugs.
6. Occurrence of adverse events, severity of adverse events and occurrence of treatment discontinuations due to tolerability of treatment.
7. Safety and tolerability of fostemsavir in the studied population, including lipids, glucose, insulin resistance (HOMA-IR) and weight, change in waist circumference.
8. Patient reported benefits of switching. To assess changes in the quality of life and perception of health (patient reported outcomes will be collected following the administration of specific questionnaires (including wellness thermometer, PHQ9, and GAD-7) in relation to the drug switch).
9. To assess change from baseline in clinical outcomes (e.g., bone health by FRAX, kidney function, cardiovascular risk, weight, BMI, and waist circumference by equation calculation). Data will be collected from routine care clinical records.
10. Rates of individuals with VL < 50 copies/mL at week 24

Conditions and MedDRA coding

HIV-1

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. HIV-1 infected adult Age > 18 years (non-childbearing potential or agrees to highly effective contraception methods)
2. On stable & suppressive cART with a VL ≤50 c/mL for 1 year allowing one blip (50-200 c/mL) as long as resuppressed below 50 for 6 consecutive months prior to enrolment and with no major adherence issues.
3. Patients on bPI with no other potential switch to another approved regimen (except to ibalizumab and/or lenacapavir, if available) due to intolerance to prior therapy or resistance.
4. No significant laboratory abnormalities, medical/psychiatric conditions or alcohol/drug use considered a barrier to participation by investigators.
5. Willing to sign an informed consent and take part in the trial.

Exclusion criteria 18

1. Age < 18 years
2. IOCBP who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the trial
3. Patients with severe hepatic impairment (Class C) as determined by Child-Pugh classification
4. Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophagael or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones)
5. History of congestive heart failure or congenital prolonged QT syndrome.
6. Confirmed QT value > 500 msec at Screening or Day 1
7. Confirmed QTcF value > 470 msec for women and > 450 msec for men at Screening or Day 1
8. ALT>5 times the ULN, OR ALT>3xULN and bilirubin>1.5xULN (with >35% direct bilirubin).
9. Any other condition (including illicit drug use or alcohol abuse) or laboratory results which, in the investigator’s opinion, interfere with assessments or completion of the trial.
10. Unable to take part in the trial according to the investigator opinion (example: unable to understand the trial information leaflet, unable to provide written consent, etc.)
11. History of being on a cART containing Fostemsavir.
12. HIV-1 subtype AE
13. Use of medications that are known to interact with Fostemsavir. Contraindications are given in appendix 3, and full information on drug-drug interactions is given in SmPC.
14. Hypersensitivity to active substance or excipient of Fostemsavir as listed in SmPC.
15. Ongoing malignancy other than cutaneous Kaposi’s sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical or anal intraepithelial neoplasia; other localised malignancies require agreement between the investigator and the Trial medical monitor for inclusion of the patient prior to trial entry
16. Known acute or chronic viral hepatitis including, but not limited to, A, B, or C. Chronic hepatitis B and history of hepatitis C (cured) are allowed.
17. Any investigational drug within 30 days prior to the trial drug administration
18. Unable to take oral medications

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To assess the proportion of patients with confirmed HIV viral load ≥50 copies/mL at week 48

Secondary endpoints 10

1. Rates of individuals with VL < 50 copies/mL at week 24 (FDA Snapshot algorithm)
2. Rates of individuals with VL < 50 copies/mL at week 48 (FDA Snapshot algorithm)
3. Rates of individuals with VL < 200 copies/mL at week 24 (FDA Snapshot algorithm)
4. Rates of individuals with VL < 200 copies/mL at week 48 (FDA Snapshot algorithm)
5. CD4 count, CD4:CD8 ratio and Lymphocyte subsets (CD4 and CD8) at week 48.
6. To evaluate the potential for drug-drug interactions in those who switch from their cART to Fostemsavir based on the University of Liverpool Drug interaction website or other sources of drug interaction knowledge, including prescribed drugs, hormones, over-the-counter medications and recreational drugs.
7. Occurrence of adverse events, severity of adverse events and occurrence of treatment discontinuations due to tolerability of treatment.
8. Safety and tolerability of Fostemsavir in the studied population, including lipids, glucose, insulin resistance (HOMA-IR) and weight, change in waist circumference.
9. Patient reported benefits of switching. To describe changes in the quality of life and perception of health (patient reported outcomes will be collected following the administration of specific questionnaires (including wellness thermometer, PHQ9, and GAD-7) in relation to the drug switch).
10. To assess change from baseline in clinical outcomes (e.g., bone health by FRAX, kidney function; cardiovascular risk, weight, BMI, and waist circumference by equation calculation). Data will be collected from routine care clinical records.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

NEAT ID Foundation

Sponsor organisation

NEAT ID Foundation

Address

Hoogstraat 322, Pl 709 Pl 709

City

Brussels

Postcode

1000

Country

Belgium

Scientific contact point

Organisation

NEAT ID Foundation

Contact name

Project Manager

Public contact point

Organisation

NEAT ID Foundation

Contact name

Project Manager

Locations

2 EU/EEA countries · 8 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 15 files

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

Application history

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