A study to investigate the safety and efficacy of fostemsavir in heavily treatment experienced people living with HIV-1 resistant to other drug classes

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Viiv Healthcare UK Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

30 Aug 2024 → ongoing

Decision date (initial)

2024-08-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ViiV Healthcare UK Limited

External identifiers

EU CT number

2024-513930-39-00

EudraCT number

2014-002111-41

WHO UTN

U1111-1161-2082

ClinicalTrials.gov

NCT02362503

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Others

To compare the efficacy of fostemsavir relative to placebo, when given on the background of a failing regimen, by determining the mean change in log10 HIV-1 RNA from Day 1 at Day 8 in the Randomized Cohort.

Secondary objectives 1

1. •To assess the efficacy of fostemsavir 600 mg BID relative to placebo, when given on the background of a failing regimen, by determining the proportions of subjects with HIV-1 RNA decreases from Day 1 that exceed 0.5 log10 c/mL and 1 log10 c/mL at Day 8 in the Randomized Cohort. •To assess the durability of the subjects’ responses to fostemsavir when given with an OBT by determining the proportion of subjects with plasma HIV-1 RNA < 40 c/mL at Week 24, Week 48, and Week 96 in the Randomized Cohort. •To assess the safety and tolerability of fostemsavir + OBT in subjects by measuring frequency of serious adverse events (SAEs), adverse events (AEs) leading to discontinuation, and Grade 3-4 laboratory abnormalities in the Randomized Cohort. •To assess disease progression during OBT as measured by the occurrence of new AIDS defining events (Centers for Disease Control [CDC] Class C events) or death in the Randomized Cohort. •To assess the emergence of antiretroviral drug resistance among subjects with protocol defined virologic failure (VF) in the Randomized Cohort. •To assess the efficacy of fostemsavir functional monotherapy, and placebo, by examining the changes from Day 1 in CD4 + T-cell counts, and the percentage of CD4 + T-cells at Day 8 in the Randomized Cohort. •To assess the efficacy of fostemsavir + OBT, by examining the changes from baseline in log10 HIV-1 RNA, CD4 + T-cell counts, and the percentage of CD4 + T-cells through Week 24, Week 48, and Week 96 in the Randomized Cohort.

Conditions and MedDRA coding

Heavily Treatment Experienced Subjects Infected with Multi-drug Resistant (MDR) HIV-1

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at https://www.gsk.com/en-gb/innovation/trials/data-transparency/Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications. Anonymized IPD is shared with researchers whose proposals are approved by an independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1) Signed and written informed consent 2) Target population: -) Men and non-pregnant women with chronic HIV-1 infection -) Age 18 and older -) Subject Re-enrollment: This study permits the re-enrollment of a subject that has discontinued the study as a pre-treatment/screen failure (ie, subject has not been randomized / has not been treated). If re-enrolled, the subject must be re-consented. and all screening requirements repeated. Re-enrollment is at the discretion of the medical monitor in discussion with PI. -) Antiretroviral-experienced with documented historical or baseline resistance, intolerability, and/or contraindications to antiretrovirals in at least three classes -) Failing current antiretroviral regimen with a confirmed plasma HIV-1 RNA of more or equal to 400 c/mL (first value from Investigator within 6 months of screening visit, with the second value obtained from Screening labs). Subjects with a screening HIV-1 RNA <400 c/mL should be counted as screen failures; repeat testing is not permissible. -) Must have at least one fully-active and available agent in < or = 2 ARV classes, based on current and/or documented historical resistance testing, taking into account tolerability and other safety concerns 3) Age and Reproductive Status -) Willingness to use approved highly effective methods of contraception to avoid pregnancy (men and women of child bearing potential only). -) Males and Females, ages 18 years of age or older (or minimum age as determined by local regulatory or as legal requirements dictate) -) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug. -) Women must not be breastfeeding -) WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with the Attachment Inhibitor and for at least 60 hours after drug exposure. -) Males, whether azoospermic or not, who are sexually active with WOCBP must use condoms and agree to follow instructions for method(s) of contraception for the duration of treatment with the Attachment Inhibitor and for at least 60 hours after drug exposure. -) WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, they must still undergo pregnancy testing as described in protocol.

Exclusion criteria 1

1. 1) Any other clinical condition (including but not limited to substance use) or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study 2) Physical and Laboratory Test Findings -) Chronic untreated HBV (however, patients with chronic treated HBV are eligible) -) HIV-2 infection -) ALT or AST > 7 x ULN -) Alkaline Phosphatase > 5 x ULN -) Bilirubin of more or = 1.5 x ULN (unless subject has Gilbert's disease, and/or is currently on atazanavir, and has predominantly unconjugated hyperbilirubinemia) -) History of decompensated cirrhosis or active decompensated cirrhosis -) History of congestive heart failure or congenital prolonged QT syndrome -) Hemoglobin < 8.0 g/dL (Randomized Cohort); Hemoglobin < 6.0 g/dL (Non-Randomized Cohort) -) Platelets < 50,000 cells/mm3 (Randomized Cohort); Platelets <20,000 cells/mm3 (Non-Randomized Cohort); -) Confirmed QT value > 500 msec at Screening or Day 1 -) Confirmed QTcF value > 470 msec for women and > 450 msec for men at Screening or Day 1 -) Confirmed PR Interval > 260 msec (severe first degree AV block) at Screening or Day 1 -) Confirmed second or third degree heart block at Screening or Day 1 -) Current or anticipated treatment with any of the following medications: rifampin, Hypericum perforatum (St. John's wort), efavirenz, nevirapine, carbemazepine, phenobarbital, phenytoin, amiodarone disopyramide, dofetilide, ibutilide, procainamide, sotalol, and quinidine. Simvastatin and lovastatin should not be co-administered with boosted protease inhibitors. -) Participation in an experimental drug and/or HIV-1 vaccine trial(s) within the previous 30 days (Randomized Cohort only) 3) Other Exclusion Criteria -) Prisoners or subjects who are involuntarily incarcerated -) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The efficacy of fostemsavir, relative to placebo, is assessed using the mean change in log10 HIV-1 RNA from Day 1 at Day 8 as determined by ANCOVA in the randomized cohort.

Secondary endpoints 1

1. •Proportions of subjects in the randomized cohort with HIV-1 RNA decreases •Durability of response at Weeks 24, 48, and 96 of OBT. •Frequency of SAEs, AEs leading to discontinuation, and Grade 3-4 laboratory abnormalities during OBT. •Disease progression during OBT. •Drug resistance testing •Changes in CD4+ T-cells counts and percentages, for Fostemsavir and placebo. •Changes from baseline in HIV-1 RNA, CD4+ cell counts, and percentage of CD4+ T-cells, for Fostemsavir when given with OBT.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Viiv Healthcare UK Limited

Sponsor organisation

Viiv Healthcare UK Limited

Address

980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Viiv Healthcare UK Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Viiv Healthcare UK Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 8

Locations

1 EU/EEA country · 2 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 6 files

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

Application history

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