Trial Outcomes & Findings for Evaluating the Safety, Pharmacokinetics, and Antiviral Activity of a Human Monoclonal Antibody (VRC01) in HIV-Infected Adults Undergoing a Brief Treatment Interruption (NCT NCT02463227)

Last Updated: 2021-10-19

Results Overview

The primary safety outcome examined the occurrence of a Grade 3 or higher systemic (i.e., not a local reaction) adverse event (AE) possibly, probably, or definitely related to the administration of the VRC01 antibody. The DAIDS AE Grading Table (V2.0) was used.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

14 participants

Primary outcome timeframe

Measured from entry through week 21 (Steps 1 and 2)

Results posted on

2021-10-19

Participant Flow

Participant milestones

Participant milestones
Measure	VRC01 Participants received an IV infusion of 40 mg/kg of VRC01 on study days 0, 21, and 42. VRC01: 40 mg/kg of VRC01 administered IV in 100 mL of 0.9% sodium chloride for injection, USP. Administered over about 30 to 60 minutes using a volumetric pump.
Overall Study STARTED	14
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluating the Safety, Pharmacokinetics, and Antiviral Activity of a Human Monoclonal Antibody (VRC01) in HIV-Infected Adults Undergoing a Brief Treatment Interruption

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	VRC01 n=14 Participants Participants received an IV infusion of 40 mg/kg of VRC01 on study days 0, 21, and 42. VRC01: 40 mg/kg of VRC01 administered IV in 100 mL of 0.9% sodium chloride for injection, USP. Administered over about 30 to 60 minutes using a volumetric pump.
Age, Continuous	38 years n=5 Participants
Age, Customized 18-29 years	1 Participants n=5 Participants
Age, Customized 30-39 years	6 Participants n=5 Participants
Age, Customized 40-49 years	6 Participants n=5 Participants
Age, Customized 50+ years	1 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
Race/Ethnicity, Customized White Non-Hispanic	6 Participants n=5 Participants
Race/Ethnicity, Customized Black Non-Hispanic	6 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic (Regardless of Race)	2 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants
Intravenous Drug History Never	13 Participants n=5 Participants
Intravenous Drug History Previously	1 Participants n=5 Participants
Weight	86 kilograms n=5 Participants
BMI	28.3 kg/m^2 n=5 Participants
HIV-1 RNA < 20 copies/mL	10 Participants n=5 Participants
HIV-1 RNA < 40 copies/mL	2 Participants n=5 Participants
HIV-1 RNA = 40 copies/mL	1 Participants n=5 Participants
HIV-1 RNA = 50600 copies/mL	1 Participants n=5 Participants
CD4 Cell Count	896 cells/mm^3 n=5 Participants

PRIMARY outcome

Timeframe: Measured from entry through week 21 (Steps 1 and 2)

Population: All participants exposed to study treatment (VRC01) were included.

Outcome measures

Outcome measures
Measure	VRC01 n=14 Participants Participants received an IV infusion of 40 mg/kg of VRC01 on study days 0, 21, and 42. VRC01: 40 mg/kg of VRC01 administered IV in 100 mL of 0.9% sodium chloride for injection, USP. Administered over about 30 to 60 minutes using a volumetric pump.
Percentage of Participants Who Experienced a Grade 3 or Higher Systemic (i.e., Not a Local Reaction) Adverse Event (AE) That is Possibly, Probably, or Definitely Related to the Administration of the VRC01 Antibody	0 percentage of participants Interval 0.0 to 23.0

PRIMARY outcome

Timeframe: Measured at Weeks 1, 2, 3, 4, 5, 6, 7, and 8 of the ATI

Population: Per protocol, the analysis population was limited to participants who received all scheduled VRC01 infusions and underwent an ATI according to protocol.

The primary efficacy outcome is the percentage of participants who had a confirmed HIV-1 RNA greater than or equal to 200 copies/mL at week 8 of the analytical treatment interruption (ATI) or indication to re-initiate ART prior to week 8 of the ATI.

Outcome measures

Outcome measures
Measure	VRC01 n=13 Participants Participants received an IV infusion of 40 mg/kg of VRC01 on study days 0, 21, and 42. VRC01: 40 mg/kg of VRC01 administered IV in 100 mL of 0.9% sodium chloride for injection, USP. Administered over about 30 to 60 minutes using a volumetric pump.
Percentage of Participants Who Had a Confirmed HIV-1 RNA Greater Than or Equal to 200 Copies/mL at Week 8 of the Analytical Treatment Interruption (ATI) or Indication to Re-initiate ART Prior to Week 8 of the ATI	92 percentage of participants Interval 68.0 to 99.6

SECONDARY outcome

Timeframe: Measured from entry through week 21 (Steps 1 and 2)

Population: Per protocol, the analysis population was limited to participants who received all scheduled VRC01 infusions and underwent an ATI according to protocol.

Measured value of plasma VRC01, measured in micrograms per milliliter, at the time of rebound. Rebound is defined as the point in time when plasma HIV-1 RNA surpassed 40 copies/mL.

Outcome measures

Outcome measures
Measure	VRC01 n=13 Participants Participants received an IV infusion of 40 mg/kg of VRC01 on study days 0, 21, and 42. VRC01: 40 mg/kg of VRC01 administered IV in 100 mL of 0.9% sodium chloride for injection, USP. Administered over about 30 to 60 minutes using a volumetric pump.
Measured Value of Plasma VRC01 at the Time of Rebound	127 micrograms/mL Interval 25.0 to 255.0

SECONDARY outcome

Timeframe: Measured at weeks 1, 2, 3, 4, 5, 6, 7, and 8 of the ATI

Population: Per protocol, the analysis population was limited to participants who received all scheduled VRC01 infusions and underwent an ATI according to protocol.

Measured values of plasma VRC01, measured in micrograms per milliliter, through week 8 of the ATI. The median and range of all VRC01 measurements taken in the first 8 weeks of the ATI were reported.

Outcome measures

Outcome measures
Measure	VRC01 n=13 Participants Participants received an IV infusion of 40 mg/kg of VRC01 on study days 0, 21, and 42. VRC01: 40 mg/kg of VRC01 administered IV in 100 mL of 0.9% sodium chloride for injection, USP. Administered over about 30 to 60 minutes using a volumetric pump.
Measured Values of VRC01 in Plasma in the First 8 Weeks of the Analytical Treatment Interruption (ATI)	175 micrograms/mL Interval 68.0 to 1494.0

SECONDARY outcome

Timeframe: Measured at weeks 1, 2, 3, and 4 of the ATI

Population: Per protocol, the analysis population was limited to participants who received all scheduled VRC01 infusions and underwent an ATI according to protocol.

The secondary efficacy outcome was the percentage of participants who had a confirmed HIV-1 RNA greater than or equal to 200 copies/mL at week 4 of the ATI or indication to reinitiate ART prior to week 4 of the ATI.

Outcome measures

Outcome measures
Measure	VRC01 n=13 Participants Participants received an IV infusion of 40 mg/kg of VRC01 on study days 0, 21, and 42. VRC01: 40 mg/kg of VRC01 administered IV in 100 mL of 0.9% sodium chloride for injection, USP. Administered over about 30 to 60 minutes using a volumetric pump.
Percentage of Participants Who Had a Confirmed HIV-1 RNA Greater Than or Equal to 200 Copies/mL at Week 4 of the ATI or Indication to Reinitiate ART Prior to Week 4 of the ATI	62 percentage of participants Interval 35.0 to 83.0

Adverse Events

VRC01

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	VRC01 n=14 participants at risk Participants received an IV infusion of 40 mg/kg of VRC01 on study days 0, 21, and 42. VRC01: 40 mg/kg of VRC01 administered IV in 100 mL of 0.9% sodium chloride for injection, USP. Administered over about 30 to 60 minutes using a volumetric pump.
Skin and subcutaneous tissue disorders Pruritus	7.1% 1/14 • Adverse event data were collected from entry throughout the study, up to week 34. The protocol required reporting of laboratory results and signs/symptoms grade ≥ 2, grade \< 2 solicited signs/symptoms from the infusion report card, laboratory results and signs/symptoms that led to a change in VRC01 infusion, and diagnoses identified by the ACTG criteria for clinical events and other diseases since the last visit. The DAIDS AE Grading Table (V2.0) and Expedited AE Manual (V2.0) were used.
Respiratory, thoracic and mediastinal disorders Wheezing	7.1% 1/14 • Adverse event data were collected from entry throughout the study, up to week 34. The protocol required reporting of laboratory results and signs/symptoms grade ≥ 2, grade \< 2 solicited signs/symptoms from the infusion report card, laboratory results and signs/symptoms that led to a change in VRC01 infusion, and diagnoses identified by the ACTG criteria for clinical events and other diseases since the last visit. The DAIDS AE Grading Table (V2.0) and Expedited AE Manual (V2.0) were used.
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	7.1% 1/14 • Adverse event data were collected from entry throughout the study, up to week 34. The protocol required reporting of laboratory results and signs/symptoms grade ≥ 2, grade \< 2 solicited signs/symptoms from the infusion report card, laboratory results and signs/symptoms that led to a change in VRC01 infusion, and diagnoses identified by the ACTG criteria for clinical events and other diseases since the last visit. The DAIDS AE Grading Table (V2.0) and Expedited AE Manual (V2.0) were used.
Respiratory, thoracic and mediastinal disorders Sinus congestion	7.1% 1/14 • Adverse event data were collected from entry throughout the study, up to week 34. The protocol required reporting of laboratory results and signs/symptoms grade ≥ 2, grade \< 2 solicited signs/symptoms from the infusion report card, laboratory results and signs/symptoms that led to a change in VRC01 infusion, and diagnoses identified by the ACTG criteria for clinical events and other diseases since the last visit. The DAIDS AE Grading Table (V2.0) and Expedited AE Manual (V2.0) were used.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.1% 1/14 • Adverse event data were collected from entry throughout the study, up to week 34. The protocol required reporting of laboratory results and signs/symptoms grade ≥ 2, grade \< 2 solicited signs/symptoms from the infusion report card, laboratory results and signs/symptoms that led to a change in VRC01 infusion, and diagnoses identified by the ACTG criteria for clinical events and other diseases since the last visit. The DAIDS AE Grading Table (V2.0) and Expedited AE Manual (V2.0) were used.
Respiratory, thoracic and mediastinal disorders Nasal congestion	7.1% 1/14 • Adverse event data were collected from entry throughout the study, up to week 34. The protocol required reporting of laboratory results and signs/symptoms grade ≥ 2, grade \< 2 solicited signs/symptoms from the infusion report card, laboratory results and signs/symptoms that led to a change in VRC01 infusion, and diagnoses identified by the ACTG criteria for clinical events and other diseases since the last visit. The DAIDS AE Grading Table (V2.0) and Expedited AE Manual (V2.0) were used.
Respiratory, thoracic and mediastinal disorders Cough	7.1% 1/14 • Adverse event data were collected from entry throughout the study, up to week 34. The protocol required reporting of laboratory results and signs/symptoms grade ≥ 2, grade \< 2 solicited signs/symptoms from the infusion report card, laboratory results and signs/symptoms that led to a change in VRC01 infusion, and diagnoses identified by the ACTG criteria for clinical events and other diseases since the last visit. The DAIDS AE Grading Table (V2.0) and Expedited AE Manual (V2.0) were used.
Nervous system disorders Hypoaesthesia	7.1% 1/14 • Adverse event data were collected from entry throughout the study, up to week 34. The protocol required reporting of laboratory results and signs/symptoms grade ≥ 2, grade \< 2 solicited signs/symptoms from the infusion report card, laboratory results and signs/symptoms that led to a change in VRC01 infusion, and diagnoses identified by the ACTG criteria for clinical events and other diseases since the last visit. The DAIDS AE Grading Table (V2.0) and Expedited AE Manual (V2.0) were used.
Nervous system disorders Headache	7.1% 1/14 • Adverse event data were collected from entry throughout the study, up to week 34. The protocol required reporting of laboratory results and signs/symptoms grade ≥ 2, grade \< 2 solicited signs/symptoms from the infusion report card, laboratory results and signs/symptoms that led to a change in VRC01 infusion, and diagnoses identified by the ACTG criteria for clinical events and other diseases since the last visit. The DAIDS AE Grading Table (V2.0) and Expedited AE Manual (V2.0) were used.
Nervous system disorders Cervical radiculopathy	7.1% 1/14 • Adverse event data were collected from entry throughout the study, up to week 34. The protocol required reporting of laboratory results and signs/symptoms grade ≥ 2, grade \< 2 solicited signs/symptoms from the infusion report card, laboratory results and signs/symptoms that led to a change in VRC01 infusion, and diagnoses identified by the ACTG criteria for clinical events and other diseases since the last visit. The DAIDS AE Grading Table (V2.0) and Expedited AE Manual (V2.0) were used.
Investigations Blood phosphorus abnormal	7.1% 1/14 • Adverse event data were collected from entry throughout the study, up to week 34. The protocol required reporting of laboratory results and signs/symptoms grade ≥ 2, grade \< 2 solicited signs/symptoms from the infusion report card, laboratory results and signs/symptoms that led to a change in VRC01 infusion, and diagnoses identified by the ACTG criteria for clinical events and other diseases since the last visit. The DAIDS AE Grading Table (V2.0) and Expedited AE Manual (V2.0) were used.
Investigations Blood glucose increased	7.1% 1/14 • Adverse event data were collected from entry throughout the study, up to week 34. The protocol required reporting of laboratory results and signs/symptoms grade ≥ 2, grade \< 2 solicited signs/symptoms from the infusion report card, laboratory results and signs/symptoms that led to a change in VRC01 infusion, and diagnoses identified by the ACTG criteria for clinical events and other diseases since the last visit. The DAIDS AE Grading Table (V2.0) and Expedited AE Manual (V2.0) were used.
Investigations Blood creatinine abnormal	7.1% 1/14 • Adverse event data were collected from entry throughout the study, up to week 34. The protocol required reporting of laboratory results and signs/symptoms grade ≥ 2, grade \< 2 solicited signs/symptoms from the infusion report card, laboratory results and signs/symptoms that led to a change in VRC01 infusion, and diagnoses identified by the ACTG criteria for clinical events and other diseases since the last visit. The DAIDS AE Grading Table (V2.0) and Expedited AE Manual (V2.0) were used.
Infections and infestations Viral upper respiratory tract infection	7.1% 1/14 • Adverse event data were collected from entry throughout the study, up to week 34. The protocol required reporting of laboratory results and signs/symptoms grade ≥ 2, grade \< 2 solicited signs/symptoms from the infusion report card, laboratory results and signs/symptoms that led to a change in VRC01 infusion, and diagnoses identified by the ACTG criteria for clinical events and other diseases since the last visit. The DAIDS AE Grading Table (V2.0) and Expedited AE Manual (V2.0) were used.
Infections and infestations Onychomycosis	7.1% 1/14 • Adverse event data were collected from entry throughout the study, up to week 34. The protocol required reporting of laboratory results and signs/symptoms grade ≥ 2, grade \< 2 solicited signs/symptoms from the infusion report card, laboratory results and signs/symptoms that led to a change in VRC01 infusion, and diagnoses identified by the ACTG criteria for clinical events and other diseases since the last visit. The DAIDS AE Grading Table (V2.0) and Expedited AE Manual (V2.0) were used.
General disorders Infusion site induration	7.1% 1/14 • Adverse event data were collected from entry throughout the study, up to week 34. The protocol required reporting of laboratory results and signs/symptoms grade ≥ 2, grade \< 2 solicited signs/symptoms from the infusion report card, laboratory results and signs/symptoms that led to a change in VRC01 infusion, and diagnoses identified by the ACTG criteria for clinical events and other diseases since the last visit. The DAIDS AE Grading Table (V2.0) and Expedited AE Manual (V2.0) were used.

Additional Information

ACTG Clinicaltrials.gov Coordinator

ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

Phone: (301) 628-3313

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place