Trial Outcomes & Findings for Romidepsin Plus 3BNC117 Phase 2a Study (NCT NCT02850016)
NCT ID: NCT02850016
Last Updated: 2022-07-14
Results Overview
Viral rebound is defined as HIV-1 RNA ≥ 200 copies/mL on 2 consecutive measurements during ATI. If viral rebound occurs, the date of the first measurement of HIV-1 RNA ≥ 200 copies/mL will be defined as "date of viral rebound
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
48 participants
Primary outcome timeframe
Week 24 to Week 36
Results posted on
2022-07-14
Participant Flow
48 participants signed informed consent. 22 met eligibility criteria and were randomized to study groups A or B in a 1:1 ratio. 2 participants withdrew consent prior to receiving the investigational products. 20 were available for analyses.
Participants were screened after signing informed consent and underwent a baseline leukapheresis procedure.
Participant milestones
| Measure |
Group A
Two treatment cycles each consisting of 3BNC117 infusions (30mg/kg) + three romidepsin infusions (5mg/m2). 3BNC117 will be administered on Days 0 and 56. Romidepsin will be administered on days 2, 9, 16, 58, 65, and 72 .
3BNC117: Intravenous Infusion of 3BNC117
Romidepsin: Intravenous Infusion of Romidepsin
|
Group B
Two treatment cycles each consisting of three romidepsin infusions (5mg/m2). Romidepsin will be administered on days 0, 7, 14, 56, 63, and 70 .
Romidepsin: Intravenous Infusion of Romidepsin
|
|---|---|---|
|
Overall Study
STARTED
|
11
|
9
|
|
Overall Study
COMPLETED
|
10
|
7
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Group A
Two treatment cycles each consisting of 3BNC117 infusions (30mg/kg) + three romidepsin infusions (5mg/m2). 3BNC117 will be administered on Days 0 and 56. Romidepsin will be administered on days 2, 9, 16, 58, 65, and 72 .
3BNC117: Intravenous Infusion of 3BNC117
Romidepsin: Intravenous Infusion of Romidepsin
|
Group B
Two treatment cycles each consisting of three romidepsin infusions (5mg/m2). Romidepsin will be administered on days 0, 7, 14, 56, 63, and 70 .
Romidepsin: Intravenous Infusion of Romidepsin
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
Baseline Characteristics
Romidepsin Plus 3BNC117 Phase 2a Study
Baseline characteristics by cohort
| Measure |
Group A
n=11 Participants
Two treatment cycles each consisting of 3BNC117 infusions (30mg/kg) + three romidepsin infusions (5mg/m2). 3BNC117 will be administered on Days 0 and 56. Romidepsin will be administered on days 2, 9, 16, 58, 65, and 72 .
3BNC117: Intravenous Infusion of 3BNC117
Romidepsin: Intravenous Infusion of Romidepsin
|
Group B
n=9 Participants
Two treatment cycles each consisting of three romidepsin infusions (5mg/m2). Romidepsin will be administered on days 0, 7, 14, 56, 63, and 70 .
Romidepsin: Intravenous Infusion of Romidepsin
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
11 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
40 years
n=5 Participants
|
51 years
n=7 Participants
|
44 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Region of Enrollment
Denmark
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
5 participants
n=5 Participants
|
4 participants
n=7 Participants
|
9 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 24 to Week 36Population: Of the 11 participants randomized to Group A, 1 chose not to interrupt ART. Of the 9 participants randomized to Group B, 1 stopped ART earlier than planned in the protocol and 1 chose not to interrupt ART.
Viral rebound is defined as HIV-1 RNA ≥ 200 copies/mL on 2 consecutive measurements during ATI. If viral rebound occurs, the date of the first measurement of HIV-1 RNA ≥ 200 copies/mL will be defined as "date of viral rebound
Outcome measures
| Measure |
Group A
n=10 Participants
Two treatment cycles each consisting of 3BNC117 infusions (30mg/kg) + three romidepsin infusions (5mg/m2). 3BNC117 will be administered on Days 0 and 56. Romidepsin will be administered on days 2, 9, 16, 58, 65, and 72 .
3BNC117: Intravenous Infusion of 3BNC117
Romidepsin: Intravenous Infusion of Romidepsin
|
Group B
n=7 Participants
Two treatment cycles each consisting of three romidepsin infusions (5mg/m2). Romidepsin will be administered on days 0, 7, 14, 56, 63, and 70 .
Romidepsin: Intravenous Infusion of Romidepsin
|
|---|---|---|
|
Days to Viral Rebound During Analytical Treatment Interruption (ATI)
|
18 days
Interval 14.0 to 28.0
|
28 days
Interval 21.0 to 35.0
|
SECONDARY outcome
Timeframe: 48 weeksPopulation: All participants who received at least a single dose of the investigational products.
The occurrence of adverse events was assessed during each follow up visit. Adverse events of grades 1 or higher were reported.
Outcome measures
| Measure |
Group A
n=11 Participants
Two treatment cycles each consisting of 3BNC117 infusions (30mg/kg) + three romidepsin infusions (5mg/m2). 3BNC117 will be administered on Days 0 and 56. Romidepsin will be administered on days 2, 9, 16, 58, 65, and 72 .
3BNC117: Intravenous Infusion of 3BNC117
Romidepsin: Intravenous Infusion of Romidepsin
|
Group B
n=9 Participants
Two treatment cycles each consisting of three romidepsin infusions (5mg/m2). Romidepsin will be administered on days 0, 7, 14, 56, 63, and 70 .
Romidepsin: Intravenous Infusion of Romidepsin
|
|---|---|---|
|
Number of of Adverse Events (AE), Serious Adverse Events (SAE), and Serious Unexpected Serious Adverse Reactions (SUSAR).
All Adverse events related to Romidepsin
|
112 events
|
66 events
|
|
Number of of Adverse Events (AE), Serious Adverse Events (SAE), and Serious Unexpected Serious Adverse Reactions (SUSAR).
All Adverse events related to 3BNC117
|
4 events
|
0 events
|
|
Number of of Adverse Events (AE), Serious Adverse Events (SAE), and Serious Unexpected Serious Adverse Reactions (SUSAR).
Grade 2 or higher Adverse Events Related to Romidepsin
|
29 events
|
5 events
|
|
Number of of Adverse Events (AE), Serious Adverse Events (SAE), and Serious Unexpected Serious Adverse Reactions (SUSAR).
Grade 2 or higher Adverse Events Related to 3BNC117
|
1 events
|
0 events
|
SECONDARY outcome
Timeframe: baseline and week 24Population: Participants who completed dosing per protocol and underwent leukapheresis at baseline and following the interventions (week 24).
Determined by total HIV-1 DNA and episomal HIV-1 DNA (2-LTR) in circulating total CD4+ T cells at baseline and prior to the ATI period (week 24).
Outcome measures
| Measure |
Group A
n=11 Participants
Two treatment cycles each consisting of 3BNC117 infusions (30mg/kg) + three romidepsin infusions (5mg/m2). 3BNC117 will be administered on Days 0 and 56. Romidepsin will be administered on days 2, 9, 16, 58, 65, and 72 .
3BNC117: Intravenous Infusion of 3BNC117
Romidepsin: Intravenous Infusion of Romidepsin
|
Group B
n=9 Participants
Two treatment cycles each consisting of three romidepsin infusions (5mg/m2). Romidepsin will be administered on days 0, 7, 14, 56, 63, and 70 .
Romidepsin: Intravenous Infusion of Romidepsin
|
|---|---|---|
|
Change in the Size of the Proviral HIV-1 Reservoir
|
58 HIV-1 DNA per million CD4+ T cells
Interval 27.0 to 482.0
|
46 HIV-1 DNA per million CD4+ T cells
Interval 0.0 to 270.0
|
SECONDARY outcome
Timeframe: 48 weeksPopulation: Participants with detectable plasma HIV-1RNA during the treatment cycles measure by commercial assays.
As measured by a routine clinical assay (Cobas Taqman; detection limit 20 copies/mL), a transcription mediated amplification (TMA)-based assay (detection limit 12 copies/ml) and/or a single copy assay (detection limit 1-2 copies/mL)
Outcome measures
| Measure |
Group A
n=11 Participants
Two treatment cycles each consisting of 3BNC117 infusions (30mg/kg) + three romidepsin infusions (5mg/m2). 3BNC117 will be administered on Days 0 and 56. Romidepsin will be administered on days 2, 9, 16, 58, 65, and 72 .
3BNC117: Intravenous Infusion of 3BNC117
Romidepsin: Intravenous Infusion of Romidepsin
|
Group B
n=9 Participants
Two treatment cycles each consisting of three romidepsin infusions (5mg/m2). Romidepsin will be administered on days 0, 7, 14, 56, 63, and 70 .
Romidepsin: Intravenous Infusion of Romidepsin
|
|---|---|---|
|
Plasma HIV-1 RNA
|
4 Participants
|
4 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: baseline and week 24Population: Participants who completed dosing according to protocol.
The median fold-change in cell-associated unspliced HIV-1 RNA concentrations after romidepsin administration across all infusions
Outcome measures
| Measure |
Group A
n=11 Participants
Two treatment cycles each consisting of 3BNC117 infusions (30mg/kg) + three romidepsin infusions (5mg/m2). 3BNC117 will be administered on Days 0 and 56. Romidepsin will be administered on days 2, 9, 16, 58, 65, and 72 .
3BNC117: Intravenous Infusion of 3BNC117
Romidepsin: Intravenous Infusion of Romidepsin
|
Group B
n=9 Participants
Two treatment cycles each consisting of three romidepsin infusions (5mg/m2). Romidepsin will be administered on days 0, 7, 14, 56, 63, and 70 .
Romidepsin: Intravenous Infusion of Romidepsin
|
|---|---|---|
|
HIV-1 Transcriptional Activity as Determined by Unspliced HIV-1 RNA (CA usHIV-1 RNA) in Circulating Total CD4+ T Cells.
|
9 CA-us HIV-1 RNA per million CD4 T cells
Interval 1.0 to 111.0
|
11 CA-us HIV-1 RNA per million CD4 T cells
Interval 5.0 to 85.0
|
Adverse Events
Group A
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Group B
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Group A
n=11 participants at risk
Two treatment cycles each consisting of 3BNC117 infusions (30mg/kg) + three romidepsin infusions (5mg/m2). 3BNC117 will be administered on Days 0 and 56. Romidepsin will be administered on days 2, 9, 16, 58, 65, and 72 .
3BNC117: Intravenous Infusion of 3BNC117
Romidepsin: Intravenous Infusion of Romidepsin
|
Group B
n=9 participants at risk
Two treatment cycles each consisting of three romidepsin infusions (5mg/m2). Romidepsin will be administered on days 0, 7, 14, 56, 63, and 70 .
Romidepsin: Intravenous Infusion of Romidepsin
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
100.0%
11/11 • Number of events 29 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
100.0%
9/9 • Number of events 9 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
|
General disorders
Headache
|
36.4%
4/11 • Number of events 13 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
33.3%
3/9 • Number of events 10 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
|
General disorders
Fatigue
|
45.5%
5/11 • Number of events 12 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
44.4%
4/9 • Number of events 4 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
|
General disorders
Chills
|
27.3%
3/11 • Number of events 8 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
22.2%
2/9 • Number of events 2 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
|
Gastrointestinal disorders
Vomiting
|
36.4%
4/11 • Number of events 8 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
22.2%
2/9 • Number of events 2 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
|
Investigations
Decreased phosphorus
|
9.1%
1/11 • Number of events 5 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
22.2%
2/9 • Number of events 5 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
|
General disorders
Malaise
|
27.3%
3/11 • Number of events 5 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
22.2%
2/9 • Number of events 6 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
27.3%
3/11 • Number of events 4 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
11.1%
1/9 • Number of events 1 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
|
Gastrointestinal disorders
Constipation
|
9.1%
1/11 • Number of events 3 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
0.00%
0/9 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
|
Renal and urinary disorders
Increased creatinine
|
18.2%
2/11 • Number of events 3 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
0.00%
0/9 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
|
Eye disorders
Xerostomia
|
27.3%
3/11 • Number of events 3 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
11.1%
1/9 • Number of events 1 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
|
Gastrointestinal disorders
Heartburn
|
18.2%
2/11 • Number of events 2 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
11.1%
1/9 • Number of events 1 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
9.1%
1/11 • Number of events 2 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
11.1%
1/9 • Number of events 3 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
|
Cardiac disorders
Neutropenia
|
18.2%
2/11 • Number of events 2 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
0.00%
0/9 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
18.2%
2/11 • Number of events 2 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
22.2%
2/9 • Number of events 2 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
|
Gastrointestinal disorders
Abdominal discomfort
|
9.1%
1/11 • Number of events 1 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
0.00%
0/9 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
|
Cardiac disorders
Prolonged QT interval
|
9.1%
1/11 • Number of events 1 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
22.2%
2/9 • Number of events 2 • 48 weeks
The definition of adverse event and/or serious adverse event DO NOT differ from the clinicaltrials.gov definitions
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place