FOSTEMSAVIR for HIV-1 infection | Multi-drug resistant HIV-1

Inclusion criteria

• {"criterion_text":"- 1) Signed and written informed consent\n- 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 \n- 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

• {"criterion_text":"- 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 \n- 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) \n- 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"}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Mean change in log10 HIV-1 RNA from Day 1 to Day 8 in the randomized cohort, analysed using ANCOVA."}

Secondary endpoints

• {"endpoint_text":"- Proportions of subjects in the randomized cohort with HIV-1 RNA decreases","definition_or_measurement_approach":"Proportions of subjects with specified decreases in HIV-1 RNA (secondary objectives specify decreases exceeding 0.5 log10 c/mL and 1 log10 c/mL at Day 8)."}
• {"endpoint_text":"- Durability of response at Weeks 24, 48, and 96 of OBT.","definition_or_measurement_approach":"Proportion of subjects with plasma HIV-1 RNA < 40 c/mL at Week 24, Week 48, and Week 96 when given with optimized background therapy (OBT)."}
• {"endpoint_text":"- Frequency of SAEs, AEs leading to discontinuation, and Grade 3-4 laboratory abnormalities during OBT.","definition_or_measurement_approach":"Safety monitored by frequency and incidence of serious adverse events, adverse events leading to discontinuation, and Grade 3-4 lab abnormalities during the OBT period."}
• {"endpoint_text":"- Disease progression during OBT.","definition_or_measurement_approach":"Assessment of new AIDS-defining events (CDC Class C events) or death during OBT."}
• {"endpoint_text":"- Drug resistance testing","definition_or_measurement_approach":"Assessment of emergence of antiretroviral drug resistance among subjects with protocol-defined virologic failure."}
• {"endpoint_text":"- Changes in CD4+ T-cells counts and percentages, for Fostemsavir and placebo.","definition_or_measurement_approach":"Changes from Day 1 in absolute CD4+ T-cell counts and percentage of CD4+ T-cells at Day 8 (and through follow-up for OBT)."}
• {"endpoint_text":"- Changes from baseline in HIV-1 RNA, CD4+ cell counts, and percentage of CD4+ T-cells, for Fostemsavir when given with OBT.","definition_or_measurement_approach":"Longitudinal changes from baseline in viral load and immune cell counts/percentages through Weeks 24, 48, and 96 while on Fostemsavir + OBT."}

Romania

Earliest CTIS Part Ii Submission Date

07-08-2024

Latest Decision Or Authorization Date

30-08-2024

Processing Time Days

23

Number Of Sites

2

Number Of Participants

5

Primary sponsor

Full Name

Viiv Healthcare UK Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

PPD Development LP

Responsibilities

Multiple sponsor duties (codes: 1,12,13,14,3,5,6,7,8,9) per CTIS record; contact EUCTRInquiry.sm@ppd.com

Name

Parexel International Corp.

Responsibilities

Sponsor duty code 10; contact Abhishek.Mishra@parexel.com

Name

Labcorp

Responsibilities

Laboratory/testing responsibilities (sponsor duties code 4); contacts provided in record

Name

Icon Laboratory Services Inc.

Responsibilities

Analysis and reporting of sCD14 & d-dimer biomarker results

Third parties

• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Sponsor duties codes: 1,12,13,14,3,5,6,7,8,9","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Monogram Biosciences Inc.","duties_or_roles":"HIV resistance testing","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Labcorp","duties_or_roles":"Sponsor duties code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"Sponsor duties code: 10","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp","duties_or_roles":"Sponsor duties code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Myriad RBM Inc.","duties_or_roles":"Analysis and reporting of SCD163 biomarker","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"Analysis and reporting of sCD14 & d-dimer biomarker results","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Provision of ECG equipment to each study site, cardiac monitoring services","organisation_type":"Pharmaceutical company"}