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

• ClinicalTrials.gov Identifier: NCT04648280
• Recruitment Status: Not yet recruiting
• First Posted: December 1, 2020
• Last Update Posted: December 1, 2020
• Sponsor: PENTA Foundation
• Collaborators: ViiV Healthcare; PHPT Foundation; Hospital Universitario 12 de Octubre; Cromsource
• Information provided by (Responsible Party): PENTA Foundation

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HIV Infections With Multi Drug Resistant Virus	Drug: Fostemsavir	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Estimated Study Start Date: June 2021
• Estimated Primary Completion Date: June 2024
• Estimated Study Completion Date: June 2027

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Occurrence of the following events through Week 24 [ Time Frame: 24 weeks ]
2. AUC(0-tau) [ Time Frame: at week 1, 4, 12, 24, 48 ]
3. Cmax [ Time Frame: at week 1, 4, 12, 24, 48 ]
4. Ctau of temsavir across weight bands [ Time Frame: at week 1, 4, 12, 24, 48 ]

Secondary Outcome Measures :

1. Proportion of patients with HIV-1 RNA <50 copies/mL [ Time Frame: at 24 weeks and 48 weeks ]
   To evaluate the antiviral activity of fostemsavir + OBT
2. Change in log10 HIV-1 RNA from baseline [ Time Frame: at 24 weeks and 48 weeks ]
3. Occurrence of: AEs, treatment-related AEs, AEs of Grade 3 or higher, serious AEs, and AEs leading to premature study treatment discontinuation. [ Time Frame: at Week 48 and at the end of Study ]
4. Occurrence of WHO 3 or 4 defining events, or death [ Time Frame: up to 156 weeks ]
5. efficacy of fostemsavir plus OBT [ Time Frame: up to 156 weeks ]
   changes from baseline in CD4+ T cell counts and the percentage of CD4 + T-cells
6. Emergence of genotypic or phenotypic resistance to Temsavir and components of OBT [ Time Frame: up to 156 weeks ]

Eligibility Criteria

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

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.

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: PENTA Foundation
• ClinicalTrials.gov Identifier: NCT04648280
• Other Study ID Numbers: SHIELD (Penta22)
• First Posted: December 1, 2020
• Last Update Posted: December 1, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Fostemsavir; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; Molecular Mechanisms of Pharmacological Action