HIV Infections With Multi Drug Resistant VirusPhase 1/2NCT04648280
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 Phase 1/2 study testing Fostemsavir in people with HIV Infections With Multi Drug Resistant Virus, run by PENTA Foundation at 8 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- HIV Infections With Multi Drug Resistant Virus
- What is being tested?
- Fostemsavir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 8 sitesin 3 countries
- Study dates
- 30 Jun 2022to Dec 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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
Show all 18Show fewer
- 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.
Trial locations and contacts
8 sites in 3 countries.
8 sites in 3 countries
South Africa5 sites
FAM-CRU
Cape Town
King Edward VIII Hospital
Durban
Rahima Moosa Mother and Child Hospital
Johannesburg, 2112
Wits Reproductive Health and HIV Institutel
Johannesburg
PHRU
Soweto
Brazil2 sites
Hospital Geral de Nova Iguaçu
Nova Iguaçu
Hospital Federal dos Servidores do Estado
Rio de Janeiro, 20221-161
United States1 site
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
About this study
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
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.
- Being tested
- Fostemsavir
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FostemsavirDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Fostemsavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of the following events through Week 24
Measured: 24 weeks
AUC(0-tau)
Measured: at week 1, 4, 12, 24, 48
Cmax
Measured: at week 1, 4, 12, 24, 48
Ctau of temsavir across weight bands
Measured: at week 1, 4, 12, 24, 48
Secondary outcomes (6)
Proportion of patients with HIV-1 RNA <50 copies/mL
To evaluate the antiviral activity of fostemsavir + OBT
Measured: at 24 weeks and 48 weeks
Change in log10 HIV-1 RNA from baseline
Measured: 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.
Measured: at Week 48 and at the end of Study
Occurrence of WHO 3 or 4 defining events, or death
Measured: up to 156 weeks
efficacy of fostemsavir plus OBT
changes from baseline in CD4+ T cell counts and the percentage of CD4 + T-cells
Measured: up to 156 weeks
Emergence of genotypic or phenotypic resistance to Temsavir and components of OBT
Measured: up to 156 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2020
- Study start30 Jun 2022
- Primary completionDec 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV Infections With Multi Drug Resistant VirusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- PENTA Foundation
- Sponsor type
- Research network
- Collaborators
- ViiV Healthcare, PHPT Foundation, Hospital Universitario 12 de Octubre, Cromsource
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04648280
- Sponsor's protocol ID
- SHIELD (Penta22)
- Status last verified
- Mar 2026
- First submitted
- 10 Nov 2020
- Last updated
- 5 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Grasa C, Salvadori N, Nardone A, Than-In-At K, Koblansky A, Parry C, Thakkar N, Wang M, Giaquinto C, Rojo P, Cressey TR. SHIELD study: 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 children and adolescents with HIV who are failing their current combination antiretroviral therapy (cART) and have dual- or triple-class antiretroviral (ARV) resistance. BMC Infect Dis. 2026 Feb 24;26(1):684. doi: 10.1186/s12879-026-12806-9.
PubMed 41735855
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04648280
- Acronym / sponsor ID
- SHIELD (Penta22)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- PENTA FoundationResearch network
- Collaborators
- ViiV Healthcare, PHPT Foundation, Hospital Universitario 12 de Octubre, Cromsource
- Study start
- 30 Jun 2022 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 1 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fostemsavir | Experimental | Drug: FostemsavirFostemsavir 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 |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fostemsavirfostemsavir 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 |
Primary outcome
Occurrence of the following events through Week 24
Time frame: 24 weeks
AUC(0-tau)
Time frame: at week 1, 4, 12, 24, 48
Cmax
Time frame: at week 1, 4, 12, 24, 48
Ctau of temsavir across weight bands
Time frame: at week 1, 4, 12, 24, 48
6 secondary outcomes
Proportion of patients with HIV-1 RNA <50 copies/mL
Time frame: at 24 weeks and 48 weeks
Change in log10 HIV-1 RNA from baseline
Time frame: 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.
Time frame: at Week 48 and at the end of Study
Occurrence of WHO 3 or 4 defining events, or death
Time frame: up to 156 weeks
efficacy of fostemsavir plus OBT
Time frame: up to 156 weeks
Emergence of genotypic or phenotypic resistance to Temsavir and components of OBT
Time frame: up to 156 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2026.
- Derived from this study: PubMed 41735855Grasa C, Salvadori N, Nardone A, Than-In-At K, Koblansky A, Parry C, Thakkar N, Wang M, Giaquinto C, Rojo P, Cressey TR. SHIELD study: 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 children and adolescents with HIV who are failing their current combination antiretroviral therapy (cART) and have dual- or triple-class antiretroviral (ARV) resistance. BMC Infect Dis. 2026 Feb 24;26(1):684. doi: 10.1186/s12879-026-12806-9.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Fostemsavir in people with HIV Infections With Multi Drug Resistant Virus, run by PENTA Foundation at 8 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 5 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in South Africa, Brazil, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of the following events through Week 24 (time frame: 24 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04648280, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2026.