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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: HIV Infections With Multi Drug Resistant Virus
• Intervention / Treatment: Drug: Fostemsavir

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Brazil
  • Nova Iguaçu, Brazil
    • Hospital Geral de Nova Iguaçu
  • Rio de Janeiro, Brazil, 20221-161
    • Hospital Federal dos Servidores do Estado
• South Africa
  • Cape Town, South Africa
    • FAM-CRU
  • Durban, South Africa
    • King Edward VIII Hospital
  • Johannesburg, South Africa, 2112
    • Rahima Moosa Mother and Child Hospital
  • Johannesburg, South Africa
    • Wits Reproductive Health and HIV Institutel
  • Soweto, South Africa
    • PHRU
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fostemsavir; 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; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with HIV-1 RNA <50 copies/mL	To evaluate the antiviral activity of fostemsavir + OBT	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	changes from baseline in CD4+ T cell counts and the percentage of CD4 + T-cells	up to 156 weeks
Emergence of genotypic or phenotypic resistance to Temsavir and components of OBT		up to 156 weeks

Collaborators and Investigators

• Sponsor: PENTA Foundation
• Collaborators: ViiV Healthcare; Hospital Universitario 12 de Octubre; Cromsource; PHPT Foundation

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2022
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: November 10, 2020
• First Submitted That Met QC Criteria: November 23, 2020
• First Posted (Actual): December 1, 2020

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; fostemsavir
• Other Study ID Numbers: SHIELD (Penta22)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No