Safety and Pharmacokinetics Evaluation of Fostemsavir + (OBT) in HIV-1 Infected Children and Adolescents Who Are Failing Their cART and Have Dual- or Triple-class Antiretroviral Resistance

NCT04648280 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: SHIELD (Penta22)
• Study Type: interventional
• Target: 60
• Locations: 3 countries
• Sites: 8

Brief Summary

In the SHIELD study, the study sponsor seeks to assess safety, PK and antiviral activity for children and adolescents with dual or triple class resistance. It will also assess the acceptability and swallowability of formulation among the pediatric population. The dose selection of FTR for children and adolescents ≥20kg utilized a population pharmacokinetic (POP PK) model-based approach to achieve similar adult TMR exposures following FTR 600mg BID administration with combination therapy that was demonstrated to be safe and effective in the FTR Phase 3 BRIGHTE study in HTE patients.

Conditions

HIV Infections With Multi Drug Resistant Virus

Outcome Measures

Primary Outcomes (4)

• Occurrence of the following events through Week 24

  24 weeks

• AUC(0-tau)

  at week 1, 4, 12, 24, 48

• Cmax

  at week 1, 4, 12, 24, 48

• Ctau of temsavir across weight bands

  at week 1, 4, 12, 24, 48

Secondary Outcomes (6)

• Proportion of patients with HIV-1 RNA <50 copies/mL

  at 24 weeks and 48 weeks

• Change in log10 HIV-1 RNA from baseline

  at 24 weeks and 48 weeks

• Occurrence of: AEs, treatment-related AEs, AEs of Grade 3 or higher, serious AEs, and AEs leading to premature study treatment discontinuation.

  at Week 48 and at the end of Study

• Occurrence of WHO 3 or 4 defining events, or death

  up to 156 weeks

• efficacy of fostemsavir plus OBT

  up to 156 weeks

Study Arms (1)

Fostemsavir

EXPERIMENTAL

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 ARV resistance

Drug: Fostemsavir

Interventions

Fostemsavir DRUG

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 ARV resistance

Fostemsavir

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• PENTA Foundation: lead
• ViiV Healthcare: collaborator
• PHPT Foundation: collaborator
• Hospital Universitario 12 de Octubre: collaborator
• Cromsource: collaborator

Study Sites (8)

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Hospital Geral de Nova Iguaçu

Nova Iguaçu, Brazil

Location

Hospital Federal dos Servidores do Estado

Rio de Janeiro, 20221-161, Brazil

Location

FAM-CRU

Cape Town, South Africa

Location

King Edward VIII Hospital

Durban, South Africa

Location

Rahima Moosa Mother and Child Hospital

Johannesburg, 2112, South Africa

Location

Wits Reproductive Health and HIV Institutel

Johannesburg, South Africa

Location

PHRU

Soweto, South Africa

Location

MeSH Terms

Interventions

fostemsavir

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2020
• First Posted: December 1, 2020
• Study Start: June 30, 2022
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (5); US (1); BR (2)