Brief Summary
The goal of this study is to test the effectiveness, safety, and tolerability of the combination of broadly neutralizing antibodies (bNAbs) (teropavimab (TAB; GS-5423) and zinlirvimab (ZAB; GS-2872)) with lenacapavir (LEN) in virologically suppressed adults with HIV-1 infection.
The purpose of this study is to evaluate the efficacy of switching to a regimen of LEN, TAB and ZAB, versus continuing on baseline oral antiretroviral therapy (ART) as determined by the proportion of participants with human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) ≥ 50 copies/mL at Week 26.
The purpose of this study is to evaluate the efficacy of switching to a regimen of LEN, TAB and ZAB, versus continuing on baseline oral antiretroviral therapy (ART) as determined by the proportion of participants with human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) ≥ 50 copies/mL at Week 26.
Brief Title
A Study of Teropavimab and Zinlirvimab in Combination With Capsid Inhibitor Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection
Detailed Description
Participants will be randomized in Treatment Groups 1 and 2 to receive LEN, TAB, and ZAB, with differing doses of TAB and ZAB between the 2 groups and in Treatment Group 3 to continue their baseline oral ART for 52 weeks. Eligible participants in Treatment Groups 1 through 3 will have the option of participating in the study extension phase to receive LEN, TAB and ZAB after completing study follow-up through Week 52.
Treatment Group 2 was removed prior to dosing of all groups during Protocol Amendment 2.
Treatment Group 2 was removed prior to dosing of all groups during Protocol Amendment 2.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
HIV Infection
Eligibility Criteria
Key Inclusion Criteria:
* On stable oral antiretroviral therapy (ART) consisting of no more than 2 drug classes (with the exception of pharmacologic boosters cobicistat or ritonavir) for ≥ 1 year prior to screening visit 2. A change in ART regimen ≥ 28 days prior to screening visit 2 for reasons other than virologic failure (VF) (eg, tolerability, simplification, drug-drug interaction profile) is allowed.
* No clinically significant documented historical resistance to the current ART regimen with the exception of isolated nucleoside reverse transcriptase inhibitor mutations including M184V or ≤ 2 thymidine analog mutations (TAMs: M41L, D67N, K70R, L210W, T215Y, and/or K219Q).
* Plasma human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) \< 50 copies/mL at screening visit 2.
* Documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 12 months preceding screening visit 2 (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Virologic elevations of ≥ 50 copies/mL (transient detectable viremia or "blips") prior to screening are acceptable.
* Proviral phenotypic sensitivity to both teropavimab and zinlirvimab at screening or from protocol GS-US-536-5816 within 24 months prior to screening.
* Screening clusters of differentiation 4 (CD4)+ T-cell count ≥ 200 cells/μL at screening visit 2.
Key Exclusion Criteria:
* Comorbid condition requiring ongoing immunosuppression.
* Evidence of hepatitis C virus (HCV) infection (prior infection cleared spontaneously or with treatment is acceptable)
* Evidence of current hepatitis B virus (HBV) infection regardless of HBV surface antigen status, at the screening visit 2.
* History of opportunistic infection or illness indicative of Stage 3 HIV disease.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
* On stable oral antiretroviral therapy (ART) consisting of no more than 2 drug classes (with the exception of pharmacologic boosters cobicistat or ritonavir) for ≥ 1 year prior to screening visit 2. A change in ART regimen ≥ 28 days prior to screening visit 2 for reasons other than virologic failure (VF) (eg, tolerability, simplification, drug-drug interaction profile) is allowed.
* No clinically significant documented historical resistance to the current ART regimen with the exception of isolated nucleoside reverse transcriptase inhibitor mutations including M184V or ≤ 2 thymidine analog mutations (TAMs: M41L, D67N, K70R, L210W, T215Y, and/or K219Q).
* Plasma human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) \< 50 copies/mL at screening visit 2.
* Documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 12 months preceding screening visit 2 (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Virologic elevations of ≥ 50 copies/mL (transient detectable viremia or "blips") prior to screening are acceptable.
* Proviral phenotypic sensitivity to both teropavimab and zinlirvimab at screening or from protocol GS-US-536-5816 within 24 months prior to screening.
* Screening clusters of differentiation 4 (CD4)+ T-cell count ≥ 200 cells/μL at screening visit 2.
Key Exclusion Criteria:
* Comorbid condition requiring ongoing immunosuppression.
* Evidence of hepatitis C virus (HCV) infection (prior infection cleared spontaneously or with treatment is acceptable)
* Evidence of current hepatitis B virus (HBV) infection regardless of HBV surface antigen status, at the screening visit 2.
* History of opportunistic infection or illness indicative of Stage 3 HIV disease.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Inclusion Criteria
Inclusion Criteria:
* On stable oral antiretroviral therapy (ART) consisting of no more than 2 drug classes (with the exception of pharmacologic boosters cobicistat or ritonavir) for ≥ 1 year prior to screening visit 2. A change in ART regimen ≥ 28 days prior to screening visit 2 for reasons other than virologic failure (VF) (eg, tolerability, simplification, drug-drug interaction profile) is allowed.
* No clinically significant documented historical resistance to the current ART regimen with the exception of isolated nucleoside reverse transcriptase inhibitor mutations including M184V or ≤ 2 thymidine analog mutations (TAMs: M41L, D67N, K70R, L210W, T215Y, and/or K219Q).
* Plasma human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) \< 50 copies/mL at screening visit 2.
* Documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 12 months preceding screening visit 2 (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Virologic elevations of ≥ 50 copies/mL (transient detectable viremia or "blips") prior to screening are acceptable.
* Proviral phenotypic sensitivity to both teropavimab and zinlirvimab at screening or from protocol GS-US-536-5816 within 24 months prior to screening.
* Screening clusters of differentiation 4 (CD4)+ T-cell count ≥ 200 cells/μL at screening visit 2.
Inclusion/
* On stable oral antiretroviral therapy (ART) consisting of no more than 2 drug classes (with the exception of pharmacologic boosters cobicistat or ritonavir) for ≥ 1 year prior to screening visit 2. A change in ART regimen ≥ 28 days prior to screening visit 2 for reasons other than virologic failure (VF) (eg, tolerability, simplification, drug-drug interaction profile) is allowed.
* No clinically significant documented historical resistance to the current ART regimen with the exception of isolated nucleoside reverse transcriptase inhibitor mutations including M184V or ≤ 2 thymidine analog mutations (TAMs: M41L, D67N, K70R, L210W, T215Y, and/or K219Q).
* Plasma human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) \< 50 copies/mL at screening visit 2.
* Documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 12 months preceding screening visit 2 (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Virologic elevations of ≥ 50 copies/mL (transient detectable viremia or "blips") prior to screening are acceptable.
* Proviral phenotypic sensitivity to both teropavimab and zinlirvimab at screening or from protocol GS-US-536-5816 within 24 months prior to screening.
* Screening clusters of differentiation 4 (CD4)+ T-cell count ≥ 200 cells/μL at screening visit 2.
Inclusion/
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
65 Years
Minimum Age
18 Years
NCT Id
NCT05729568
Org Class
Industry
Org Full Name
Gilead Sciences
Org Study Id
GS-US-536-5939
Overall Status
Active, not recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 2 Randomized, Open-label Study to Evaluate the Safety and Efficacy of Broadly Neutralizing Antibodies (bNAbs) GS-5423 and GS-2872 in Combination With the Capsid Inhibitor Lenacapavir as Long-Acting Treatment Dosed Every 6 Months in Virologically Suppressed Adults With HIV-1 Infection
Primary Outcomes
Outcome Description
Percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 26 was analyzed using US FDA-defined snapshot algorithm, which defines a participant's virologic outcome and included participants a) who had last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 26 analysis window; b) who did not have on-treatment HIV-1 RNA data in the Week 26 analysis window and i) discontinued study drug prior to or in the Week 26 analysis window due to lack of efficacy, or ii) discontinued study drug prior to or in the Week 26 analysis window due to adverse event (AE) or death and had last available on-treatment HIV-1 RNA ≥ 50 copies/mL, or iii) discontinued study drug prior to or in the Week 26 analysis window due to reasons other than AE, death, or lack of efficacy and had the last available on-treatment HIV-1 RNA ≥ 50 copies/mL.
Clopper-Pearson exact method was used to calculate the 95% confidence interval (CI) for the outcome measure of each treatment. Percentages were rounded off.
Clopper-Pearson exact method was used to calculate the 95% confidence interval (CI) for the outcome measure of each treatment. Percentages were rounded off.
Outcome Measure
Percentage of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) ≥ 50 Copies/mL at Week 26 as Determined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm
Outcome Time Frame
Week 26
Secondary Outcomes
Outcome Time Frame
Week 52
Outcome Measure
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 52 as Determined by the US FDA-defined Snapshot Algorithm
Outcome Description
Percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 26 was analyzed using the US FDA-defined snapshot algorithm, which defined a participant's virologic outcome and included participants who had the last available on-treatment HIV-1 RNA \< 50 copies/mL in the Week 26 analysis window.
The Clopper-Pearson exact method was used to calculate the 95% CI for the outcome measure of each treatment. Percentages were rounded off.
The Clopper-Pearson exact method was used to calculate the 95% CI for the outcome measure of each treatment. Percentages were rounded off.
Outcome Time Frame
Week 26
Outcome Measure
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm
Outcome Time Frame
Week 52
Outcome Measure
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 52 as Determined by the US FDA-defined Snapshot Algorithm
Outcome Time Frame
Baseline, Week 26
Outcome Measure
Change From Baseline in Clusters of Differentiation 4 (CD4) + T-cell Counts at Week 26
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change From Baseline in CD4+ T-cell Counts at Week 52
Outcome Time Frame
Up to approximately 6 years
Outcome Measure
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Outcome Description
Trough concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.
Outcome Time Frame
Week 26
Outcome Measure
Trough Concentration at Week 26 for TAB and ZAB
Outcome Description
Trough concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.
Outcome Time Frame
Week 26
Outcome Measure
Trough Concentration at Week 26 for LEN
Outcome Description
Trough concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.
Outcome Time Frame
Week 52
Outcome Measure
Trough Concentration at Week 52 for TAB and ZAB
Outcome Description
Trough concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.
Outcome Time Frame
Week 52
Outcome Measure
Trough Concentration at Week 52 for LEN
Outcome Description
AUC0-tau is defined as the partial area under the concentration versus time curve from time "0" to time "t".
Outcome Time Frame
Up to approximately 6 years
Outcome Measure
Pharmacokinetic (PK) Parameter: AUC0-tau for TAB and ZAB
Outcome Description
t1/2 is defined as the terminal elimination half-life.
Outcome Time Frame
Up to approximately 6 years
Outcome Measure
PK Parameter: t1/2 for TAB and ZAB
Outcome Description
Cmax is defined as the maximum observed concentration of drug.
Outcome Time Frame
Up to approximately 6 years
Outcome Measure
PK Parameter: Cmax for TAB and ZAB
Outcome Description
Cmax is defined as the maximum observed concentration of drug.
Outcome Time Frame
Up to approximately 6 years
Outcome Measure
PK Parameter: Cmax for LEN
Outcome Description
Tmax is defined as the time (observed time point) of Cmax.
Outcome Time Frame
Up to approximately 6 years
Outcome Measure
PK Parameter: Tmax for TAB, ZAB, and LEN
Outcome Description
Anti-TAB and anti-ZAB antibodies incidence referred to the percentage of participants who have treatment-emergent anti-TAB and anti-ZAB antibodies among all participants evaluable for anti-drug antibody (ADA) incidence.
Outcome Time Frame
Up to approximately 6 years
Outcome Measure
Percentage of Participants With Treatment-emergent Anti-TAB and Anti-ZAB Antibodies
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
65
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Robert Grossberg
Investigator Email
rgrossbe@montefiore.org
Investigator Phone
718-920-5276