HIV Infections
Conditions
Brief summary
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.
Detailed description
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.
Interventions
30 mg tablets administered orally
NRTIs were not provided by the study. Participants obtained NRTIs outside of the study through routine care.
600 mg loading dose followed by 400 mg maintenance doses administered by intramuscular (IM) injection
BIOLOGICALVRC07-523LS
40 mg/kg administered as an intravenous (IV) infusion
DRUGStandard of Care (SOC) ART
SOC ART was not provided by the study. Participants obtained SOC ART outside of the study through routine care.
Sponsors
ViiV Healthcare
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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: * A negative serum or urine pregnancy test within 48 hours prior to study entry * If participating in sexual activity that could lead to pregnancy, must agree to use an effective form of contraception. * Negative HBsAg result * Negative hepatitis C virus antibody * Ability and willingness to provide written informed consent Step 1
Exclusion criteria
* Any previous receipt of humanized or human monoclonal antibody (licensed or investigational). * Weight greater than 115 kg or less than 53 kg. * AIDS-defining illness within 60 days prior to study entry. * History of a severe allergic reaction within 2 years prior to study entry. * Currently breastfeeding or pregnant. * Active drug or alcohol use or dependence that would interfere with adherence to study requirements. * Acute or serious illness that requires systemic treatment, quarantine, and/or hospitalization within 30 days prior to entry. * Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 60 days prior to study entry. * Treatment for hepatitis C within 24 weeks prior to study entry. * Vaccinations within 7 days prior to study entry. * Initiation of ART during acute HIV-1 infection (as determined by the site investigator by history and/or available medical records). * Personal or known family history of prolonged QT syndrome or a clinically significant finding on the screening electrocardiogram (ECG) based on an assessment of the screening ECG by that site investigator. * Unstable liver disease or known biliary abnormalities * Moderate or severe hepatic impairment (Class B or C) as determined by Child-Pugh classification. * History of seizures or treatment for seizures within the past 2 years prior to study entry. * Current acute illness that in the opinion of the investigator will prevent the participant from complying with study visits. 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: * A negative serum or urine pregnancy test within 48 hours prior to step 2 entry * If participating in sexual activity that could lead to pregnancy, continued agreement to use an effective form of contraception. Step 2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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). | 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 |
| Cumulative Probability of Confirmed Virologic Failure at or Prior to Step 2 Week 44 | Measured from Step 2 entry through 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ARV Resistance of Breakthrough Isolates | Measured from Step 2 entry through Step 2 Week 48 | 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). |
| Cumulative Probability of Confirmed Virologic Failure at or Prior to Step 2 Week 24 | Measured from Step 2 entry through Step 2 Week 24 | Virologic failure defined as confirmed (i.e., two consecutive values) HIV-1 RNA ≥ 200 copies/mL |
| Cumulative Probability of Confirmed Virologic Failure or Premature Treatment Discontinuation at or Prior to Step 2 Week 44 | Measured from Step 2 entry through 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. |
| Cumulative Probability of Confirmed HIV-1 RNA ≥ 50 Copies/mL at or Prior to Step 2 Week 44 | Measured from Step 2 entry through 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. |
| Cumulative Probability of Confirmed HIV-1 RNA ≥ 50 Copies/mL at or Prior to Step 2 Week 24 | Measured from Step 2 entry through 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. |
| Median Concentrations of VRC07-523LS | Measured at Step 2 Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 | Concentrations of VRC07-523LS, measured in serum, at selected time points in Step 2. |
| Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Step 2 Week 44 | 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. |
| Frequency of Anti-Drug Antibodies (ADA) Against VRC07-523LS | Measured at Step 2 Week 28 and 48 | Number of participants who were anti-drug antibody (ADA) negative or ADA positive calculated at each sampled timepoint. |
| 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. | Measured from Step 1 entry through the end of Step 1 (for a maximum of 5 weeks) | 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. |
| Proportion of Participants Who Prematurely Discontinued Oral CAB 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) | The proportion of participants who discontinued, for any reason, oral CAB (during Step 1) or the CAB LA plus VRC07-523LS combination. |
| 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. | Measured from Step 1 entry through entire study follow-up (for a maximum of 101 weeks) | 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. |
| Cumulative Probability of Confirmed HIV-1 RNA ≥ 50 Copies/mL or Premature Treatment Discontinuation at or Prior to Step 2 Week 44 | Measured from Step 2 entry through 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. |
| Median Concentration of CAB LA | Measured at Step 2 Week 4, 8, 24, and 48 | Concentrations of long-acting cabotegravir, measured in plasma, at select time points in Step 2 |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
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.
Pre-assignment details
There was no randomization in this study.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 74 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Step 1 (Oral CAB + 2 NRTIs) | Determined to be ineligible | 1 |
| Step 2 (CAB LA + VRC07-523LS) | Adverse Event | 1 |
| Step 2 (CAB LA + VRC07-523LS) | Death | 1 |
| Step 2 (CAB LA + VRC07-523LS) | Participant refusal to remain on long-acting treatment | 3 |
| Step 2 (CAB LA + VRC07-523LS) | Virologic failure, as defined by the protocol | 5 |
| Step 2 (CAB LA + VRC07-523LS) | Withdrawal by Subject | 1 |
| Step 3 (SOC ART) | Death | 1 |
| Step 3 (SOC ART) | Participant moved | 1 |
Baseline characteristics
| Characteristic | CAB LA + VRC07-523LS |
|---|---|
| Age, Continuous | 54 years |
| Baseline BMI | 28 kg/m^2 |
| Baseline CD4 cell count | 720 cells/mm^3 |
| Baseline HIV-1 RNA Greater than or equal to 50 copies/mL | 3 Participants |
| Baseline HIV-1 RNA Less than 50 copies/mL | 71 Participants |
| Race/Ethnicity, Customized Black (Non-Hispanic) | 25 Participants |
| Race/Ethnicity, Customized Hispanic or Latino (regardless of race) | 8 Participants |
| Race/Ethnicity, Customized Other | 3 Participants |
| Race/Ethnicity, Customized White (Non-Hispanic) | 38 Participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 55 Participants |
| VRC07-523LS IC50 | 0.076 ug/mL |
| VRC07-523LS MPI | 99.9 Percent |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 74 | 1 / 71 | 1 / 68 |
| other Total, other adverse events | 9 / 74 | 37 / 71 | 29 / 68 |
| serious Total, serious adverse events | 1 / 74 | 9 / 71 | 6 / 68 |
Outcome results
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.
Time frame: Measured from Step 2 entry through Step 2 Week 44
Population: All participants who initiated the CAB LA plus VRC07-523LS combination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CAB LA + VRC07-523LS | Cumulative Probability of Confirmed Virologic Failure at or Prior to Step 2 Week 44 | 0.07 Cumulative probability |
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
Time frame: 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).
Population: All participants who initiated the CAB LA plus VRC07-523LS combination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CAB LA + VRC07-523LS | 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) | 0.17 Proportion of participants |
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).
Time frame: Measured from Step 2 entry through Step 2 Week 48
Population: 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.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CAB LA + VRC07-523LS | ARV Resistance of Breakthrough Isolates | Susceptible | 3 Participants |
| CAB LA + VRC07-523LS | ARV Resistance of Breakthrough Isolates | Intermediate or Low-Level Resistance | 1 Participants |
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.
Time frame: Measured from Step 2 entry through Step 2 Week 24
Population: All participants who initiated the CAB LA plus VRC07-523LS combination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CAB LA + VRC07-523LS | Cumulative Probability of Confirmed HIV-1 RNA ≥ 50 Copies/mL at or Prior to Step 2 Week 24 | 0.12 Cumulative probability |
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.
Time frame: Measured from Step 2 entry through Step 2 Week 44
Population: All participants who intiated the CAB LA plus VRC07-523LS combination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CAB LA + VRC07-523LS | Cumulative Probability of Confirmed HIV-1 RNA ≥ 50 Copies/mL at or Prior to Step 2 Week 44 | 0.13 Cumulative probability |
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.
Time frame: Measured from Step 2 entry through Step 2 Week 44
Population: All participants who initiated the CAB LA plus VRC07-523LS combination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CAB LA + VRC07-523LS | Cumulative Probability of Confirmed HIV-1 RNA ≥ 50 Copies/mL or Premature Treatment Discontinuation at or Prior to Step 2 Week 44 | 0.20 Cumulative probability |
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
Time frame: Measured from Step 2 entry through Step 2 Week 24
Population: All participants who initiated the CAB LA plus VRC07-523LS combination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CAB LA + VRC07-523LS | Cumulative Probability of Confirmed Virologic Failure at or Prior to Step 2 Week 24 | 0.04 Cumulative probability |
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.
Time frame: Measured from Step 2 entry through Step 2 Week 44
Population: All participants initiating the CAB LA plus VRC07-523LS combination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CAB LA + VRC07-523LS | Cumulative Probability of Confirmed Virologic Failure or Premature Treatment Discontinuation at or Prior to Step 2 Week 44 | 0.14 Cumulative probability |
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.
Time frame: Measured at Step 2 Week 28 and 48
Population: All participants who initiated the CAB LA plus VRC07-523LS combination and had ADA samples obtained at the scheduled study visit were included.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| CAB LA + VRC07-523LS | Frequency of Anti-Drug Antibodies (ADA) Against VRC07-523LS | Step 2 Week 28 | ADA Negative | 61 Participants |
| CAB LA + VRC07-523LS | Frequency of Anti-Drug Antibodies (ADA) Against VRC07-523LS | Step 2 Week 28 | ADA Positive | 0 Participants |
| CAB LA + VRC07-523LS | Frequency of Anti-Drug Antibodies (ADA) Against VRC07-523LS | Step 2 Week 48 | ADA Negative | 59 Participants |
| CAB LA + VRC07-523LS | Frequency of Anti-Drug Antibodies (ADA) Against VRC07-523LS | Step 2 Week 48 | ADA Positive | 0 Participants |
Secondary
Median Concentration of CAB LA
Concentrations of long-acting cabotegravir, measured in plasma, at select time points in Step 2
Time frame: Measured at Step 2 Week 4, 8, 24, and 48
Population: All participants who initiated the CAB LA plus VRC07-523LS combination and had PK samples obtained at the scheduled study visits were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CAB LA + VRC07-523LS | Median Concentration of CAB LA | Step 2 Week 4 | 1398 ng/mL |
| CAB LA + VRC07-523LS | Median Concentration of CAB LA | Step 2 Week 8 | 1714 ng/mL |
| CAB LA + VRC07-523LS | Median Concentration of CAB LA | Step 2 Week 24 | 2386 ng/mL |
| CAB LA + VRC07-523LS | Median Concentration of CAB LA | Step 2 Week 48 | 2760 ng/mL |
Secondary
Median Concentrations of VRC07-523LS
Concentrations of VRC07-523LS, measured in serum, at selected time points in Step 2.
Time frame: Measured at Step 2 Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
Population: All participants who initiated the CAB LA plus VRC07-523LS combination and had PK samples obtained at the scheduled study visits were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CAB LA + VRC07-523LS | Median Concentrations of VRC07-523LS | Step 2 Week 4 | 177 ug/mL |
| CAB LA + VRC07-523LS | Median Concentrations of VRC07-523LS | Step 2 Week 8 | 105 ug/mL |
| CAB LA + VRC07-523LS | Median Concentrations of VRC07-523LS | Step 2 Week 12 | 232 ug/mL |
| CAB LA + VRC07-523LS | Median Concentrations of VRC07-523LS | Step 2 Week 16 | 146 ug/mL |
| CAB LA + VRC07-523LS | Median Concentrations of VRC07-523LS | Step 2 Week 20 | 261 ug/mL |
| CAB LA + VRC07-523LS | Median Concentrations of VRC07-523LS | Step 2 Week 24 | 151 ug/mL |
| CAB LA + VRC07-523LS | Median Concentrations of VRC07-523LS | Step 2 Week 28 | 264 ug/mL |
| CAB LA + VRC07-523LS | Median Concentrations of VRC07-523LS | Step 2 Week 32 | 161 ug/mL |
| CAB LA + VRC07-523LS | Median Concentrations of VRC07-523LS | Step 2 Week 36 | 269 ug/mL |
| CAB LA + VRC07-523LS | Median Concentrations of VRC07-523LS | Step 2 Week 40 | 156 ug/mL |
| CAB LA + VRC07-523LS | Median Concentrations of VRC07-523LS | Step 2 Week 44 | 266 ug/mL |
| CAB LA + VRC07-523LS | Median Concentrations of VRC07-523LS | Step 2 Week 48 | 166 ug/mL |
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.
Time frame: Measured from Step 1 entry through the end of Step 1 (for a maximum of 5 weeks)
Population: All eligible participants who initiated oral CAB.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CAB LA + VRC07-523LS | 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. | 0 Proportion of participants |
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.
Time frame: Measured from Step 1 entry through entire study follow-up (for a maximum of 101 weeks)
Population: All eligible participants who initiated oral CAB and all participants who initiated the CAB LA plus VRC07-523LS combination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CAB LA + VRC07-523LS | 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. | 0.15 Proportion of participants |
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.
Time frame: Measured from Step 1 entry through the end of Step 2 (for a maximum of 53 weeks)
Population: All eligible participants who initiated Step 1 (oral CAB) and all participants who initiated Step 2 (CAB LA plus VRC07-523LS) treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CAB LA + VRC07-523LS | Proportion of Participants Who Prematurely Discontinued Oral CAB or the CAB LA Plus VRC07-523LS Combination | 10 Participants |
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.
Time frame: Step 2 Week 44
Population: All participants who initiated the CAB LA plus VRC07 combination.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CAB LA + VRC07-523LS | Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Step 2 Week 44 | No Virologic Data in Week 44 Window: Disc study/study drug for other reasons | 2 Participants |
| CAB LA + VRC07-523LS | Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Step 2 Week 44 | No Virologic Data in Week 44 Window: On study but missing data in window | 1 Participants |
| CAB LA + VRC07-523LS | Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Step 2 Week 44 | HIV-1 RNA ≥ 50 copies/mL on treatment | 7 Participants |
| CAB LA + VRC07-523LS | Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Step 2 Week 44 | HIV-1 RNA < 50 copies/mL on treatment | 58 Participants |
| CAB LA + VRC07-523LS | Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Step 2 Week 44 | No Virologic Data in Week 44 Window: Disc study/study drug due to an AE or death | 3 Participants |