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| ID | Type | Description | Link |
|---|---|---|---|
| 30005 | Registry Identifier | DAIDS-ES Registry Number |
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| Name | Class |
|---|---|
| ViiV Healthcare | INDUSTRY |
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The purpose of this study was to assess the safety, tolerability, antiviral activity, and pharmacokinetics of long-acting cabotegravir (CAB LA) plus the broadly neutralizing monoclonal antibody VRC-HIVMAB075-00-AB (VRC07-523LS), in adults living with HIV-1 with suppressed plasma viremia.
This study had a single, open-label arm and was conducted in three steps.
At Step 1 entry, all participants discontinued their current antiretroviral therapy (ART) regimen, except for the 2 nucleoside reverse transcriptase inhibitors (NRTIs) and started oral CAB. Viral load monitoring occurred at entry, Week 4, and, conditionally, Week 5.
During Step 1, participants who tolerated oral CAB plus their two NRTIs, maintained viral suppression, and met the other Step 2 eligibility requirements, registered for Step 2. Participants in Step 1 who were not eligible for Step 2 returned to their standard of care (SOC) regimen and were followed for an additional 4 weeks before being taken off the study.
In Step 2, participants received CAB LA every 4 weeks through Step 2 Week 44 (12 injections) plus VRC07-523LS every 8 weeks through Step 2 Week 40 (6 infusions). Viral load monitoring occurred every 2 weeks through Week 8 and then every 4 weeks through Week 48. Any participant with a viral load of HIV-1 RNA ≥ 200 copies/mL had to attend an additional virologic failure confirmation visit within 14 days of the measured value. If virologic failure was confirmed (i.e., two consecutive HIV-1 RNA values ≥ 200 copies/mL), the participant transitioned to Step 3.
After completion of Step 2 (Week 48), confirmed virologic failure, or premature treatment discontinuation, all participants who received any CAB LA or VRC07-523LS entered Step 3 and returned to SOC ART for 48 weeks, with visits at step entry and weeks 4, 12, 24, 36, and 48.
The study's primary virology outcome pertains to Step 2 and only includes participants who started the CAB LA plus VRC07-523LS combination. The study's primary safety outcome pertains to Step 2 and Step 3 follow-up for participants who started the CAB LA plus VRC07-523LS combination.
Study visits included physical examinations, clinical assessments, and blood and urine collection.
The study opened to accrual in late December 2019. However, in March 2020 the study temporarily closed to screening and enrollment (including registration to Step 2) due to the COVID-19 pandemic. No participant had reached Step 2 of the study when the pause occurred. Participants in Step 1 were instructed to immediately stop the oral CAB plus 2 NRTI combination, resume their SOC regimen, and discontinue the study. The study reopened to screening and enrollment in September 2020. Analyses for this study only included participants who enrolled after the study reopened in September 2020. Participants previously enrolled were invited to rescreen and reenroll, if still eligible.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CAB LA + VRC07-523LS | Experimental | Step 1: CAB administered orally as one 30 mg tablet once daily, plus two NRTIs, for up to 5 weeks. Step 2: CAB LA loading dose (600 mg) administered as one IM injection at Step 2 entry study visit, and maintenance dose (400 mg), starting at 4 weeks after CAB LA loading dose, and then every 4 weeks through Week R2+44 (for a total of 12 injections). VRC07-523LS (40 mg/kg) administered as an IV infusion starting at Step 2 entry and then every 8 weeks through Week R2+40 (for a total of 6 infusions). Step 3: Standard of Care (SOC) ART regimen for approximately 48 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oral Cabotegravir (CAB) | Drug | 30 mg tablets administered orally |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) or Premature Discontinuation Due to an AE (Regardless of Grade) That is Related To Step 2 Study Treatment (CAB LA Plus VRC07-523LS) | The proportion of participants reporting a grade 3 (severe), grade 4 (potentially life-threatening), or grade 5 (death) adverse event OR premature discontinuation due to an adverse event (regardless of grade) that the clinical management committee judged to be at least possibly related to the CAB LA plus VRC07-523LS combination. Based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017 | Measured from Step 2 entry through the remaining study follow-up (e.g., any time on Step 2 or Step 3 for a maximum follow-up time of 96 weeks). |
| Cumulative Probability of Confirmed Virologic Failure at or Prior to Step 2 Week 44 | Virologic failure is defined as confirmed (i.e., two consecutive values) HIV-1 RNA ≥ 200 copies/mL at or prior to Step 2 Week 44 of the CAB LA plus VRC07-523LS combination. | Measured from Step 2 entry through Step 2 Week 44 |
| Measure | Description | Time Frame |
|---|---|---|
| Median Concentrations of VRC07-523LS | Concentrations of VRC07-523LS, measured in serum, at selected time points in Step 2. | Measured at Step 2 Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 |
| Median Concentration of CAB LA |
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Step 1 Inclusion Criteria:
Individual with HIV-1
On a three-drug ART regimen for at least 8 weeks that includes a boosted protease inhibitor (PI), a nonnuceloside reverse transcriptase inhibitor (NNRTI), or an integrase inhibitor (INSTI) plus two nuclesodie reverse transcriptase inhibitors (NRTI) with no history of switch due to virologic failure.
CD4+ cell count greater than or equal to 350 cells/mm^3
Virally suppressed (< 50 copies/mL) within 2 years prior to study entry
Susceptibility to VRC07-523LS based on IC50 less than or equal to 0.25 ug/mL and a Maximum Percent Inhibition > 98% using the Monogram PhenoSense Assay
Certain laboratory values obtained within 60 days prior to study entry and in an acceptable range
For participants of child-bearing potential:
Negative HBsAg result
Negative hepatitis C virus antibody
Ability and willingness to provide written informed consent
Step 1 Exclusion Criteria:
Step 2 Inclusion Criteria:
HIV-1 RNA less than 50 copies/mL at week 4 (Step 1), or HIV-1 RNA of 50-199 copies/mL at week 4 followed by HIV-1 RNA less than 50 copies/mL at week 5 (Step 1).
For participants of child-bearing potential:
Step 2 Exclusion Criteria:
Step 3 Inclusion Criterion:
Step 3 Exclusion Criterion:
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| Name | Affiliation | Role |
|---|---|---|
| Babafemi Taiwo, MBBS | Northwestern University CRS | Study Chair |
| Pablo Tebas, MD | Hospital of the University of Pennsylvania CRS | Study Chair |
| Leah Burke, MD | Weill Cornell Chelsea CRS | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alabama CRS | Birmingham | Alabama | 35294 | United States | ||
| UCSD Antiviral Research Center CRS |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37265259 | Derived | Kuritzkes DR. Broadly neutralizing antibodies and long-acting antiretroviral drugs as treatments for HIV. Curr Opin HIV AIDS. 2023 Jul 1;18(4):225-228. doi: 10.1097/COH.0000000000000801. Epub 2023 May 9. |
| Label | URL |
|---|---|
| The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017 | View source |
Not provided
Individual participant data that underlie results in the publication, after deidentification.
Beginning 3 months following publication and available throughout period of funding of the Advancing Clinical Therapeutics Globally (ACTG) by NIH.
With whom?
For what types of analyses?
By what mechanism will data be made available?
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There was no randomization in this study.
Participants enrolled from Dec 2019 to May 2022 at 18 sites in the United States. In Mar 2020 the study temporarily closed to screening and enrollment. During this pause, all participants were taken off the study. The study reopened to screening and enrollment in mid-September 2020. Analyses only included participants who enrolled after the study reopened. All previously enrolled participants were encouraged to return and rescreen.
Note: Not all participants who entered Step 1, entered Step 2.
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| ID | Title | Description |
|---|---|---|
| FG000 | CAB LA + VRC07-523LS | Step 1: CAB administered orally as one 30 mg tablet once daily, plus two NRTIs, for up to 5 weeks. Step 2: CAB LA loading dose (600 mg) administered as one IM injection at Step 2 entry study visit, and maintenance dose (400 mg), starting at 4 weeks after CAB LA loading dose, and then every 4 weeks through Week R2+44 (for a total of 12 injections). VRC07-523LS (40 mg/kg) administered as an IV infusion starting at Step 2 entry and then every 8 weeks through Week R2+40 (for a total of 6 infusions). Step 3: Standard of Care (SOC) ART regimen for approximately 48 weeks. Oral Cabotegravir (CAB): 30 mg tablets administered orally Nucleoside Reverse Transcriptase Inhibitors (NRTIs): NRTIs were not provided by the study. Participants obtained NRTIs outside of the study through routine care. Long-Acting Injectable Cabotegravir (CAB LA): 600 mg loading dose followed by 400 mg maintenance doses administered by intramuscular (IM) injection VRC07-523LS: 40 mg/kg administered as an intravenous (IV) infusion Standard of Care (SOC) ART: SOC ART was not provided by the study. Participants obtained SOC ART outside of the study through routine care. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Step 1 (Oral CAB + 2 NRTIs) |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_ICF | Yes | No | Yes | Study Protocol and Informed Consent Form | Mar 11, 2022 |
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| Nucleoside Reverse Transcriptase Inhibitors (NRTIs) |
| Drug |
NRTIs were not provided by the study. Participants obtained NRTIs outside of the study through routine care. |
|
| Long-Acting Injectable Cabotegravir (CAB LA) | Drug | 600 mg loading dose followed by 400 mg maintenance doses administered by intramuscular (IM) injection |
|
| VRC07-523LS | Biological | 40 mg/kg administered as an intravenous (IV) infusion |
|
|
| Standard of Care (SOC) ART | Drug | SOC ART was not provided by the study. Participants obtained SOC ART outside of the study through routine care. |
|
Concentrations of long-acting cabotegravir, measured in plasma, at select time points in Step 2
| Measured at Step 2 Week 4, 8, 24, and 48 |
| ARV Resistance of Breakthrough Isolates | ARV resistance testing was conducted on samples obtained when confirmed virologic failure (two consecutive HIV-1 RNA values ≥ 200 copies/mL) occurred. Interpretation of resistance results, pertaining to integrase inhibitor resistance mutations, was obtained using the Stanford HIVDB Algorithm Version 9.3 (released 2022-11-20). | Measured from Step 2 entry through Step 2 Week 48 |
| Cumulative Probability of Confirmed Virologic Failure at or Prior to Step 2 Week 24 | Virologic failure defined as confirmed (i.e., two consecutive values) HIV-1 RNA ≥ 200 copies/mL | Measured from Step 2 entry through Step 2 Week 24 |
| Cumulative Probability of Confirmed Virologic Failure or Premature Treatment Discontinuation at or Prior to Step 2 Week 44 | Virologic failure, defined as confirmed (i.e., two consecutive values) HIV-1 RNA ≥ 200 copies/mL or premature treatment discontinuation, defined as the date at which a participant ended Step 2 treatment (CAB LA and VRC07-523LS), for any reason, without receiving all 12 CAB LA injections and 6 VRC07-523LS infusions, at or prior to Step 2 Week 44. | Measured from Step 2 entry through Step 2 Week 44 |
| Cumulative Probability of Confirmed HIV-1 RNA ≥ 50 Copies/mL at or Prior to Step 2 Week 44 | Confirmed (i.e., two consecutive values) HIV-1 RNA ≥ 50 copies/mL measured at or prior to Step 2 Week 44. | Measured from Step 2 entry through Step 2 Week 44 |
| Cumulative Probability of Confirmed HIV-1 RNA ≥ 50 Copies/mL at or Prior to Step 2 Week 24 | Confirmed (i.e., two consecutive values) HIV-1 RNA ≥ 50 copies/mL measured at or prior to Step 2 Week 24. | Measured from Step 2 entry through Step 2 Week 24 |
| Cumulative Probability of Confirmed HIV-1 RNA ≥ 50 Copies/mL or Premature Treatment Discontinuation at or Prior to Step 2 Week 44 | Confirmed (i.e., two consecutive values) HIV-1 RNA ≥ 50 copies/mL or premature treatment discontinuation, defined as the date at which a participant ended Step 2 treatment (CAB LA and VRC07-523LS), for any reason, without receiving all 12 CAB LA injections and 6 VRC07-523LS infusions, at or prior to Step 2 Week 44. | Measured from Step 2 entry through Step 2 Week 44 |
| Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Step 2 Week 44 | The proportion of participants with HIV-1 RNA ≥ 50 copies/mL, HIV-1 RNA < 50 copies/mL, and without data in Step 2 Week 44 window (days 295-322 from Step 2 entry) as defined by the FDA Snapshot algorithm. | Step 2 Week 44 |
| Frequency of Anti-Drug Antibodies (ADA) Against VRC07-523LS | Number of participants who were anti-drug antibody (ADA) negative or ADA positive calculated at each sampled timepoint. | Measured at Step 2 Week 28 and 48 |
| Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) or Premature Discontinued Due to an AE (Regardless of Grade) That is Related to Oral CAB. | The proportion of participants reporting a grade 3 (severe), grade 4 (potentially life-threatening), or grade 5 (death) adverse event OR premature discontinuation due to an adverse event (regardless of grade) that the clinical management committee judged to be at least possibly related to oral CAB. Based on the Division of AIDS Table for Grading the Severity of Adult and Pedatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. | Measured from Step 1 entry through the end of Step 1 (for a maximum of 5 weeks) |
| Proportion of Participants Who Prematurely Discontinued Oral CAB or the CAB LA Plus VRC07-523LS Combination | The proportion of participants who discontinued, for any reason, oral CAB (during Step 1) or the CAB LA plus VRC07-523LS combination. | Measured from Step 1 entry through the end of Step 2 (for a maximum of 53 weeks) |
| Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) That is Related to Oral CAB or the CAB LA Plus VRC07-523LS Combination. | The proportion of participants reporting a grade 3 (severe), grade 4 (potentially life-threatening), or grade 5 (death) that the clinical management committee judged to be at least possibly related to oral CAB or the CAB LA plus VRC07-523LS combination. Based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. | Measured from Step 1 entry through entire study follow-up (for a maximum of 101 weeks) |
| San Diego |
| California |
| 92103 |
| United States |
| Ucsf Hiv/Aids Crs | San Francisco | California | 94110 | United States |
| University of Colorado Hospital CRS | Aurora | Colorado | 80045 | United States |
| Northwestern University CRS | Chicago | Illinois | 60611 | United States |
| Johns Hopkins University CRS | Baltimore | Maryland | 21205 | United States |
| Washington University Therapeutics (WT) CRS | St Louis | Missouri | 63110-1010 | United States |
| New Jersey Medical School Clinical Research Center CRS | Newark | New Jersey | 07103 | United States |
| Weill Cornell Chelsea CRS | New York | New York | 10010 | United States |
| Columbia P&S CRS | New York | New York | 10032-3732 | United States |
| Weill Cornell Uptown CRS | New York | New York | 10065 | United States |
| University of Rochester Adult HIV Therapeutic Strategies Network CRS | Rochester | New York | 14642 | United States |
| Chapel Hill CRS | Chapel Hill | North Carolina | 27599 | United States |
| Cincinnati Clinical Research Site | Cincinnati | Ohio | 45219 | United States |
| Ohio State University CRS | Columbus | Ohio | 43210 | United States |
| Penn Therapeutics, CRS | Philadelphia | Pennsylvania | 19104 | United States |
| University of Washington AIDS CRS | Seattle | Washington | 98104-9929 | United States |
| Puerto Rico AIDS Clinical Trials Unit CRS | San Juan | 00935 | Puerto Rico |
| Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010 | View source |
| Completed Step 1 and Enrolled to Step 2 |
|
| Completed Step 1 and Discontinued the Study |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Step 2 (CAB LA + VRC07-523LS) |
|
|
| Step 3 (SOC ART) |
|
|
75 participants were enrolled to the study. One participant enrolled erroneously despite not meeting the eligibility criteria for VRC07-523LS susceptibility. This participant discontinued the study during Step 1 and is excluded from all analyses.
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| ID | Title | Description |
|---|---|---|
| BG000 | CAB LA + VRC07-523LS | Step 1: CAB administered orally as one 30 mg tablet once daily, plus two NRTIs, for up to 5 weeks. Step 2: CAB LA loading dose (600 mg) administered as one IM injection at Step 2 entry study visit, and maintenance dose (400 mg), starting at 4 weeks after CAB LA loading dose, and then every 4 weeks through Week R2+44 (for a total of 12 injections). VRC07-523LS (40 mg/kg) administered as an IV infusion starting at Step 2 entry and then every 8 weeks through Week R2+40 (for a total of 6 infusions). Step 3: Standard of Care (SOC) ART regimen for approximately 48 weeks. Oral Cabotegravir (CAB): 30 mg tablets administered orally Nucleoside Reverse Transcriptase Inhibitors (NRTIs): NRTIs were not provided by the study. Participants obtained NRTIs outside of the study through routine care. Long-Acting Injectable Cabotegravir (CAB LA): 600 mg loading dose followed by 400 mg maintenance doses administered by intramuscular (IM) injection VRC07-523LS: 40 mg/kg administered as an intravenous (IV) infusion Standard of Care (SOC) ART: SOC ART was not provided by the study. Participants obtained SOC ART outside of the study through routine care. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Inter-Quartile Range | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||||
| Baseline BMI | Median | Inter-Quartile Range | kg/m^2 |
| |||||||||||||||||
| Baseline HIV-1 RNA | Count of Participants | Participants |
| ||||||||||||||||||
| Baseline CD4 cell count | One participant had a missing CD4 count at study entry. | Median | Inter-Quartile Range | cells/mm^3 |
| ||||||||||||||||
| VRC07-523LS IC50 | The IC50 represents the VRC07-523LS concentration needed to inhibit viral replication by 50%. | Median | Full Range | ug/mL |
| ||||||||||||||||
| VRC07-523LS MPI | The Maximum Percent Inhibition (MPI) refers to the highest level of viral replication inhibition achieved by a specific VRC07-523LS concentration. | Median | Full Range | Percent |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) or Premature Discontinuation Due to an AE (Regardless of Grade) That is Related To Step 2 Study Treatment (CAB LA Plus VRC07-523LS) | The proportion of participants reporting a grade 3 (severe), grade 4 (potentially life-threatening), or grade 5 (death) adverse event OR premature discontinuation due to an adverse event (regardless of grade) that the clinical management committee judged to be at least possibly related to the CAB LA plus VRC07-523LS combination. Based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017 | All participants who initiated the CAB LA plus VRC07-523LS combination | Posted | Number | 95% Confidence Interval | Proportion of participants | Measured from Step 2 entry through the remaining study follow-up (e.g., any time on Step 2 or Step 3 for a maximum follow-up time of 96 weeks). |
|
|
| |||||||||||||||||||||||||
| Primary | Cumulative Probability of Confirmed Virologic Failure at or Prior to Step 2 Week 44 | Virologic failure is defined as confirmed (i.e., two consecutive values) HIV-1 RNA ≥ 200 copies/mL at or prior to Step 2 Week 44 of the CAB LA plus VRC07-523LS combination. | All participants who initiated the CAB LA plus VRC07-523LS combination | Posted | Number | 95% Confidence Interval | Cumulative probability | Measured from Step 2 entry through Step 2 Week 44 |
| |||||||||||||||||||||||||||
| Secondary | Median Concentrations of VRC07-523LS | Concentrations of VRC07-523LS, measured in serum, at selected time points in Step 2. | All participants who initiated the CAB LA plus VRC07-523LS combination and had PK samples obtained at the scheduled study visits were included. | Posted | Median | Inter-Quartile Range | ug/mL | Measured at Step 2 Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 |
| |||||||||||||||||||||||||||
| Secondary | Median Concentration of CAB LA | Concentrations of long-acting cabotegravir, measured in plasma, at select time points in Step 2 | All participants who initiated the CAB LA plus VRC07-523LS combination and had PK samples obtained at the scheduled study visits were included. | Posted | Median | Inter-Quartile Range | ng/mL | Measured at Step 2 Week 4, 8, 24, and 48 |
| |||||||||||||||||||||||||||
| Secondary | ARV Resistance of Breakthrough Isolates | ARV resistance testing was conducted on samples obtained when confirmed virologic failure (two consecutive HIV-1 RNA values ≥ 200 copies/mL) occurred. Interpretation of resistance results, pertaining to integrase inhibitor resistance mutations, was obtained using the Stanford HIVDB Algorithm Version 9.3 (released 2022-11-20). | Participants with confirmed virologic failure (two consecutive HIV-1 RNA values ≥ 200 copies/mL) who initiated the VRC07-523LS + CAB LA combination and had reportable assay results. | Posted | Count of Participants | Participants | Measured from Step 2 entry through Step 2 Week 48 |
| ||||||||||||||||||||||||||||
| Secondary | Cumulative Probability of Confirmed Virologic Failure at or Prior to Step 2 Week 24 | Virologic failure defined as confirmed (i.e., two consecutive values) HIV-1 RNA ≥ 200 copies/mL | All participants who initiated the CAB LA plus VRC07-523LS combination | Posted | Number | 95% Confidence Interval | Cumulative probability | Measured from Step 2 entry through Step 2 Week 24 |
| |||||||||||||||||||||||||||
| Secondary | Cumulative Probability of Confirmed Virologic Failure or Premature Treatment Discontinuation at or Prior to Step 2 Week 44 | Virologic failure, defined as confirmed (i.e., two consecutive values) HIV-1 RNA ≥ 200 copies/mL or premature treatment discontinuation, defined as the date at which a participant ended Step 2 treatment (CAB LA and VRC07-523LS), for any reason, without receiving all 12 CAB LA injections and 6 VRC07-523LS infusions, at or prior to Step 2 Week 44. | All participants initiating the CAB LA plus VRC07-523LS combination | Posted | Number | 95% Confidence Interval | Cumulative probability | Measured from Step 2 entry through Step 2 Week 44 |
| |||||||||||||||||||||||||||
| Secondary | Cumulative Probability of Confirmed HIV-1 RNA ≥ 50 Copies/mL at or Prior to Step 2 Week 44 | Confirmed (i.e., two consecutive values) HIV-1 RNA ≥ 50 copies/mL measured at or prior to Step 2 Week 44. | All participants who intiated the CAB LA plus VRC07-523LS combination | Posted | Number | 95% Confidence Interval | Cumulative probability | Measured from Step 2 entry through Step 2 Week 44 |
| |||||||||||||||||||||||||||
| Secondary | Cumulative Probability of Confirmed HIV-1 RNA ≥ 50 Copies/mL at or Prior to Step 2 Week 24 | Confirmed (i.e., two consecutive values) HIV-1 RNA ≥ 50 copies/mL measured at or prior to Step 2 Week 24. | All participants who initiated the CAB LA plus VRC07-523LS combination | Posted | Number | 95% Confidence Interval | Cumulative probability | Measured from Step 2 entry through Step 2 Week 24 |
| |||||||||||||||||||||||||||
| Secondary | Cumulative Probability of Confirmed HIV-1 RNA ≥ 50 Copies/mL or Premature Treatment Discontinuation at or Prior to Step 2 Week 44 | Confirmed (i.e., two consecutive values) HIV-1 RNA ≥ 50 copies/mL or premature treatment discontinuation, defined as the date at which a participant ended Step 2 treatment (CAB LA and VRC07-523LS), for any reason, without receiving all 12 CAB LA injections and 6 VRC07-523LS infusions, at or prior to Step 2 Week 44. | All participants who initiated the CAB LA plus VRC07-523LS combination | Posted | Number | 95% Confidence Interval | Cumulative probability | Measured from Step 2 entry through Step 2 Week 44 |
| |||||||||||||||||||||||||||
| Secondary | Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Step 2 Week 44 | The proportion of participants with HIV-1 RNA ≥ 50 copies/mL, HIV-1 RNA < 50 copies/mL, and without data in Step 2 Week 44 window (days 295-322 from Step 2 entry) as defined by the FDA Snapshot algorithm. | All participants who initiated the CAB LA plus VRC07 combination. | Posted | Count of Participants | Participants | Step 2 Week 44 |
| ||||||||||||||||||||||||||||
| Secondary | Frequency of Anti-Drug Antibodies (ADA) Against VRC07-523LS | Number of participants who were anti-drug antibody (ADA) negative or ADA positive calculated at each sampled timepoint. | All participants who initiated the CAB LA plus VRC07-523LS combination and had ADA samples obtained at the scheduled study visit were included. | Posted | Count of Participants | Participants | Measured at Step 2 Week 28 and 48 |
| ||||||||||||||||||||||||||||
| Secondary | Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) or Premature Discontinued Due to an AE (Regardless of Grade) That is Related to Oral CAB. | The proportion of participants reporting a grade 3 (severe), grade 4 (potentially life-threatening), or grade 5 (death) adverse event OR premature discontinuation due to an adverse event (regardless of grade) that the clinical management committee judged to be at least possibly related to oral CAB. Based on the Division of AIDS Table for Grading the Severity of Adult and Pedatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. | All eligible participants who initiated oral CAB. | Posted | Number | 95% Confidence Interval | Proportion of participants | Measured from Step 1 entry through the end of Step 1 (for a maximum of 5 weeks) |
| |||||||||||||||||||||||||||
| Secondary | Proportion of Participants Who Prematurely Discontinued Oral CAB or the CAB LA Plus VRC07-523LS Combination | The proportion of participants who discontinued, for any reason, oral CAB (during Step 1) or the CAB LA plus VRC07-523LS combination. | All eligible participants who initiated Step 1 (oral CAB) and all participants who initiated Step 2 (CAB LA plus VRC07-523LS) treatment | Posted | Count of Participants | Participants | Measured from Step 1 entry through the end of Step 2 (for a maximum of 53 weeks) |
| ||||||||||||||||||||||||||||
| Secondary | Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) That is Related to Oral CAB or the CAB LA Plus VRC07-523LS Combination. | The proportion of participants reporting a grade 3 (severe), grade 4 (potentially life-threatening), or grade 5 (death) that the clinical management committee judged to be at least possibly related to oral CAB or the CAB LA plus VRC07-523LS combination. Based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. | All eligible participants who initiated oral CAB and all participants who initiated the CAB LA plus VRC07-523LS combination | Posted | Number | 95% Confidence Interval | Proportion of participants | Measured from Step 1 entry through entire study follow-up (for a maximum of 101 weeks) |
|
Step 1: From study entry through step completion or premature discontinuation of study/Step 1 (maximum time in Step 1 was 5 weeks). Step 2: From Step 2 entry through step completion or premature discontinuation of study/Step 2 (maximum time in Step 2 was 48 weeks). Step 3: From Step 3 entry through study completion of premature discontinuation (maximum time in Step 3 was 48 weeks).
The DAIDS AE Grading Table (V2.1), July 2017 was used. All eligible participants who entered Step 1 are included. For eligible participants who entered Step 2, AEs occurring in Step 2 are shown separately. All participants in Step 2 were eligible for Step 3. AEs occurring in Step 3 are shown in a separate column.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Step 1: Oral CAB Plus 2 NRTIs | Step 1: CAB administered orally as one 30 mg tablet once daily, plus two NRTIs, for up to 5 weeks. Oral Cabotegravir (CAB): 30 mg tablets administered orally Nucleoside Reverse Transcriptase Inhibitors (NRTIs): NRTIs were not provided by the study. Participants obtained NRTIs outside of the study through routine care. | 0 | 74 | 1 | 74 | 9 | 74 |
| EG001 | Step 2: CAB LA + VRC07-523LS | Step 2: CAB LA loading dose (600 mg) administered as one IM injection at Step 2 entry study visit, and maintenance dose (400 mg), starting at 4 weeks after CAB LA loading dose, and then every 4 weeks through Week R2+44 (for a total of 12 injections). VRC07-523LS (40 mg/kg) administered as an IV infusion starting at Step 2 entry and then every 8 weeks through Week R2+40 (for a total of 6 infusions). Long-Acting Injectable Cabotegravir (CAB LA): 600 mg loading dose followed by 400 mg maintenance doses administered by intramuscular (IM) injection VRC07-523LS: 40 mg/kg administered as an intravenous (IV) infusion | 1 | 71 | 9 | 71 | 37 | 71 |
| EG002 | Step 3: Standard of Care ART | Step 3: Standard of Care (SOC) ART regimen for approximately 48 weeks. Standard of Care (SOC) ART: SOC ART was not provided by the study. Participants obtained SOC ART outside of the study through routine care. | 1 | 68 | 6 | 68 | 29 | 68 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute coronary syndrome | Cardiac disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Bacterial sepsis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Escherichia bacteraemia | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Neurosyphilis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Overdose | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Toxicity to various agents | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Intraductal proliferative breast lesion | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Systematic Assessment |
| |
| Lung adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Systematic Assessment |
| |
| Prostate cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Systematic Assessment |
| |
| Uterine leiomyoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 26.0 | Systematic Assessment |
| |
| Suicide attempt | Psychiatric disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Emphysema | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Pneumomediastinum | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| Comminuted fracture | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Wrist fracture | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Blood bilirubin | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Blood cholesterol increased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Blood creatine phosphokinase | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Blood creatinine decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Blood glucose decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Blood pressure increased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Creatinine renal clearance decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Low density lipoprotein increased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| Abnormal loss of weight | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Tension headache | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 26.0 | Systematic Assessment |
| |
| Vasospasm | Vascular disorders | MedDRA 26.0 | Systematic Assessment |
|
This single-arm trial was conducted during the COVID-19 and Mpox public health emergencies, which prompted several countermeasures, including widespread use of multiple doses of new vaccines that can potentially impact virologic response.
In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| ACTG Clinicaltrials.gov Coordinator | ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company | ACTG Network Coordinating Cent | ACTGCT.gov@fstrf.org |
| Jan 16, 2025 |
| Prot_ICF_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 22, 2023 | Mar 31, 2025 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C584914 | cabotegravir |
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
Not provided
Not provided
| Virologic failure, as defined by the protocol |
|
| Participant refusal to remain on long-acting treatment |
|
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| Hispanic or Latino (regardless of race) |
|
| Other |
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