Evaluating Fostemsavir for HIV-1 Infected Children and Adolescents with Drug Resistance

A Multicenter, Open-label, Single-arm Trial to Evaluate the Safety, Pharmacokinetics and Antiviral Activity of Fostemsavir in Combination with Optimized Background Therapy (OBT) in HIV-1 Infected Children and Adolescents Who Are Failing Their Current Combination Antiretroviral Therapy (cART) and Have Dual- or Triple-class Antiretroviral (ARV) Resistance

This study is testing a new HIV medication called Fostemsavir in children and teens aged 6 to under 18 who have trouble with their current treatments to see if it can help them feel better.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 6 Years to 17 Years
• Sex: All
• Sponsor: PENTA Foundation (Research network)
• Locations: 10 sites (Washington, District of Columbia and 9 other locations)
• Trial ID: NCT04648280 on ClinicalTrials.gov

What this trial studies

This study aims to assess the safety, pharmacokinetics, and antiviral activity of Fostemsavir in children and adolescents aged 6 to under 18 years who are experiencing treatment failure due to dual or triple-class antiretroviral resistance. Participants will receive a tailored dose of Fostemsavir based on a population pharmacokinetic model to ensure effective exposure similar to adults. The study will also evaluate the acceptability and swallowability of the medication formulation among the pediatric population. The goal is to identify a safe and effective treatment option for this vulnerable group.

Who should consider this trial

Good fit: Ideal candidates are HIV-1 infected children and adolescents aged 6 to less than 18 years who have documented resistance to multiple antiretroviral classes and are failing their current treatment regimen.

Not a fit: Patients who are not experiencing treatment failure or do not have documented resistance to multiple antiretroviral classes may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new effective treatment option for children and adolescents with multi-drug resistant HIV.

How similar studies have performed: Other studies have shown success with similar approaches in adult populations, but this specific application in pediatric patients is novel.

Eligibility criteria

Inclusion Criteria:

* Male and female HIV-1 infected paediatric participants from 6 years old and weighing at least 20 kg to less than 18 years of age.
* Antiretroviral-experienced with documented historical or baseline resistance to one or more agents in at least two classes. All resistance has to be properly documented.
* Failing current antiretroviral regimen with a confirmed plasma HIV-1 RNA ≥ 1000 c/mL (first value from Investigator within 6 months of screening visit, with the second value obtained from Screening labs, without a decline greater than 1 log10, and no value \<1000 in between).
* Documented resistance to at least one component of the current failing regimen per screening resistance testing.
* Must have at least 1 fully active and available agent in 2 or more ARV classes, based on current and/or documented historical resistance testing, taking into account tolerability, and other safety concerns. At least two fully active agents must be a part of the initial OBT to be paired with FTR.
* Girls who have reached menarche must have a negative pregnancy test at screening, not be breastfeeding, and be willing to adhere to effective methods of contraception if sexually active. All participants (male or female) have to agree with recommendations for effective contraception.

Exclusion Criteria:

Medical History and Concurrent Diseases:

* Unable to comply with dosing requirements (to swallow solid pharmaceutical form of the investigational medicinal product)
* Unable to comply with study visits
* Presence of a malabsorption syndrome or other gastrointestinal dysfunction which might interfere with drug absorption or render the participant unable to take oral medication.
* Any clinical condition (including but not limited to recreational drug use) or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study
* Pregnancy and breastfeeding

Physical and Laboratory Test Findings:

* Chronic untreated Hepatitis B virus (HBV) (however, participants with chronic treated HBV or spontaneously remitted HBV are eligible)
* HIV-2 infection
* Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN), OR ALT ≥3xULN and bilirubin ≥1.5xULN (with\>35% direct bilirubin)
* History of unstable liver disease, decompensated cirrhosis, or known biliary disorder
* History of congestive heart failure, or congenital/acquired prolonged QT syndrome/other cardiac diseases predisposing to prolonged QTc
* Hemoglobin \< 8.0 g/dL
* Platelets \< 50,000 cells/mm3
* Confirmed QTcF value \> 450 msec, regardless of sex, at Screening or Day 1
* Current (defined as taking the medication within 14 days of Day 1) or anticipated treatment with medication considered prohibited or restricted as per Appendix II. Certain medication will be carefully evaluated as acceptable, see Appendix II.
* Participation in an experimental drug and/or HIV-1 vaccine trial(s) within the previous 30 days
* Child in governmental care, e.g. child is a ward of the state. Note: This criterion does not apply if the child is officially adopted by a family/guardian.

Where this trial is running

Washington, District of Columbia and 9 other locations

• The George Washington University, Children's National Health System — Washington, District of Columbia, United States (Recruiting)
• Children's Healthcare of Atlanta — Atlanta, Georgia, United States (Recruiting)
• Hospital Geral de Nova Iguaçu — Nova iguaçu, Brazil (Not_yet_recruiting)
• Hospital Federal dos Servidores do Estado — Rio de Janeiro, Brazil (Not_yet_recruiting)
• Fam-Cru — Cape Town, South Africa (Recruiting)
• King Edward VIII Hospital — Durban, South Africa (Recruiting)
• Rahima Moosa Mother and Child Hospital — Johannesburg, South Africa (Recruiting)
• Wits Reproductive Health and HIV Institutel — Johannesburg, South Africa (Recruiting)
• Kalafong Hospital — Pretoria, South Africa (Not_yet_recruiting)
• Phru — Soweto, South Africa (Recruiting)

Study contacts

• Study coordinator: Pablo Rojo

Conditions HIV Infections with Multi Drug Resistant Virus