Trial Outcomes & Findings for Safety and Pharmacokinetic Study of Dapivirine Gel (0.05%) Administered Rectally to HIV-1 Seronegative Adults (NCT NCT03239483)

Last Updated: 2021-10-19

Results Overview

As defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 and/or Addenda 1, 2 and 3 (Female Genital \[Dated November 2007\], Male Genital \[Dated November 2007\] and Rectal \[Clarification Dated May 2012\] Grading Tables for Use in Microbicide Studies)

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

28 participants

Primary outcome timeframe

Measured after the participant has started study product until the participant's study termination at approximately Day 40

Results posted on

2021-10-19

Participant Flow

Participant milestones

Participant milestones
Measure	Dapivirine Gel Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic. Dapivirine gel: Dapivirine gel (0.05%); administered rectally	Placebo Gel Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic. Placebo gel: Universal HEC placebo gel; administered rectally
Overall Study STARTED	19	9
Overall Study COMPLETED	17	9
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Dapivirine Gel Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic. Dapivirine gel: Dapivirine gel (0.05%); administered rectally	Placebo Gel Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic. Placebo gel: Universal HEC placebo gel; administered rectally
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Safety and Pharmacokinetic Study of Dapivirine Gel (0.05%) Administered Rectally to HIV-1 Seronegative Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dapivirine Gel n=19 Participants Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic. Dapivirine gel: Dapivirine gel (0.05%); administered rectally	Placebo Gel n=9 Participants Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic. Placebo gel: Universal HEC placebo gel; administered rectally	Total n=28 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=93 Participants	9 Participants n=4 Participants	28 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Continuous	26 years n=93 Participants	35 years n=4 Participants	33 years n=27 Participants
Sex: Female, Male Female	4 Participants n=93 Participants	5 Participants n=4 Participants	9 Participants n=27 Participants
Sex: Female, Male Male	15 Participants n=93 Participants	4 Participants n=4 Participants	19 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=93 Participants	9 Participants n=4 Participants	27 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	7 Participants n=93 Participants	4 Participants n=4 Participants	11 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	3 Participants n=4 Participants	4 Participants n=27 Participants
Race (NIH/OMB) White	11 Participants n=93 Participants	2 Participants n=4 Participants	13 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	13 participants n=93 Participants	6 participants n=4 Participants	19 participants n=27 Participants
Region of Enrollment Thailand	6 participants n=93 Participants	3 participants n=4 Participants	9 participants n=27 Participants

PRIMARY outcome

Timeframe: Measured after the participant has started study product until the participant's study termination at approximately Day 40

Population: enrolled participants receiving at least one dose of study product

Outcome measures

Outcome measures
Measure	Dapivirine Gel n=18 Participants Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic. Dapivirine gel: Dapivirine gel (0.05%); administered rectally	Placebo Gel n=9 Participants Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic. Placebo gel: Universal HEC placebo gel; administered rectally
Frequency of Grade 2 or Higher Adverse Events (AEs)	3 Participants	5 Participants

PRIMARY outcome

Timeframe: Sample collected at approximately 1, 2, 24, 48 and 72 hours after first single dose, 24 hours after first dose during daily dosing, before last dose and 1,2, 24,48, and 72 hours after last dose.

Population: enrolled participants on the Dapivirine arm who received at least one dose of study product and had a sample collected at the specific time-point. 0 is an estimate for values below the limit of quantification (LLOQ = 20 pg/mL) since only numeric values are allowed. The value would be somewhere between the LLOQ and 0.

As assessed by pharmacokinetic sampling and analysis

Outcome measures

Outcome measures
Measure	Dapivirine Gel n=18 Participants Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic. Dapivirine gel: Dapivirine gel (0.05%); administered rectally	Placebo Gel Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic. Placebo gel: Universal HEC placebo gel; administered rectally
Measurement of Dapivirine Concentrations in Plasma 30 to 60 minutes after single dose	31.5 pg/mL Interval 0.0 to 54.6	—
Measurement of Dapivirine Concentrations in Plasma 120 minutes after single dose	326 pg/mL Interval 153.0 to 481.0	—
Measurement of Dapivirine Concentrations in Plasma 24 hours after single dose	20.1 pg/mL Interval 0.0 to 56.6	—
Measurement of Dapivirine Concentrations in Plasma 48 hours after single dose	0 pg/mL Interval 0.0 to 27.3	—
Measurement of Dapivirine Concentrations in Plasma 72 hours after single dose	0 pg/mL Interval 0.0 to 0.0	—
Measurement of Dapivirine Concentrations in Plasma 24 hours after first daily dose	67.9 pg/mL Interval 43.1 to 111.0	—
Measurement of Dapivirine Concentrations in Plasma Before last daily dose	167 pg/mL Interval 136.0 to 219.0	—
Measurement of Dapivirine Concentrations in Plasma 30 to 60 minutes after last daily dose	290.5 pg/mL Interval 147.0 to 506.5	—
Measurement of Dapivirine Concentrations in Plasma 120 minutes after last daily dose	403 pg/mL Interval 330.0 to 493.0	—
Measurement of Dapivirine Concentrations in Plasma 24 hours after last daily dose	119.0 pg/mL Interval 86.4 to 172.0	—
Measurement of Dapivirine Concentrations in Plasma 48 hours after last daily dose	113 pg/mL Interval 69.0 to 132.0	—
Measurement of Dapivirine Concentrations in Plasma 72 hours after last daily dose	80.3 pg/mL Interval 47.3 to 129.0	—

PRIMARY outcome

Timeframe: Sample collected at approximately 1, 2, 24, 48 and 72 hours after first single dose, 24 hours after first dose during daily dosing, and 1,2, 24,48, and 72 hours after last dose.

Population: enrolled participants on the Dapivirine arm who received at least one dose of product and had a sample collected at the specific time-point. 0 is an estimate for values below the limit of quantification (LLOQ = 0.001 ng/mg) since only numeric values are allowed. The value would be somewhere between the lower limit of quantification and 0.

As assessed by pharmacokinetic rectal fluid sampling and analysis

Outcome measures

Outcome measures
Measure	Dapivirine Gel n=18 Participants Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic. Dapivirine gel: Dapivirine gel (0.05%); administered rectally	Placebo Gel Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic. Placebo gel: Universal HEC placebo gel; administered rectally
Measurement of Dapivirine Concentrations in Rectal Fluid 30 to 60 minutes after first application	30.1 ng/mg Interval 16.1 to 43.9	—
Measurement of Dapivirine Concentrations in Rectal Fluid 120 minutes after single dose	12.765 ng/mg Interval 6.055 to 141.5	—
Measurement of Dapivirine Concentrations in Rectal Fluid 24 hours after single dose	0 ng/mg Interval 0.0 to 0.016	—
Measurement of Dapivirine Concentrations in Rectal Fluid 48 hours after single dose	0.009 ng/mg Interval 0.0 to 0.038	—
Measurement of Dapivirine Concentrations in Rectal Fluid 72 hours after single dose	0 ng/mg Interval 0.0 to 0.0	—
Measurement of Dapivirine Concentrations in Rectal Fluid 24 hours after first daily dose	0.180 ng/mg Interval 0.0 to 1.91	—
Measurement of Dapivirine Concentrations in Rectal Fluid 30 to 60 minutes after last daily dose	89.7 ng/mg Interval 44.9 to 258.0	—
Measurement of Dapivirine Concentrations in Rectal Fluid 120 minutes after last daily dose	26.65 ng/mg Interval 4.95 to 278.5	—
Measurement of Dapivirine Concentrations in Rectal Fluid 24 hours after last daily dose	0.007 ng/mg Interval 0.0 to 0.096	—
Measurement of Dapivirine Concentrations in Rectal Fluid 48 hours after last daily dose	0 ng/mg Interval 0.0 to 0.042	—
Measurement of Dapivirine Concentrations in Rectal Fluid 72 hours after last daily dose	0 ng/mg Interval 0.0 to 0.013	—

PRIMARY outcome

Timeframe: Sample collected at approximately 1, 2, 24, 48 and 72 hours after first single dose and 1,2, 24,48, and 72 hours after last dose.

Population: enrolled participants on the Dapivirine gel arm who received at least one dose of study product and had a sample collected at the specific time-point. 0 is an estimate for values below the limit of quantification (LLOQ = 0.001 ng/mg) since only numeric values are allowed. The value would be somewhere between the LLOQ and 0.

As assessed by pharmacokinetic rectal mucosal tissue homogenates sampling and analysis

Outcome measures

Outcome measures
Measure	Dapivirine Gel n=18 Participants Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic. Dapivirine gel: Dapivirine gel (0.05%); administered rectally	Placebo Gel Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic. Placebo gel: Universal HEC placebo gel; administered rectally
Measurement of Dapivirine Concentrations in Rectal Mucosal Tissue Homogenates 30 to 60 minutes after single dose	0.256 ng/mg Interval 0.0 to 0.666	—
Measurement of Dapivirine Concentrations in Rectal Mucosal Tissue Homogenates 120 minutes after single dose	0 ng/mg Interval 0.0 to 0.6	—
Measurement of Dapivirine Concentrations in Rectal Mucosal Tissue Homogenates 24 hours after single dose	0 ng/mg Interval 0.0 to 0.0	—
Measurement of Dapivirine Concentrations in Rectal Mucosal Tissue Homogenates 48 hours after single dose	0 ng/mg Interval 0.0 to 0.0	—
Measurement of Dapivirine Concentrations in Rectal Mucosal Tissue Homogenates 72 hours after single dose	0 ng/mg Interval 0.0 to 0.0	—
Measurement of Dapivirine Concentrations in Rectal Mucosal Tissue Homogenates 30 to 60 minutes after last daily dose	0 ng/mg Interval 0.0 to 0.0	—
Measurement of Dapivirine Concentrations in Rectal Mucosal Tissue Homogenates 120 minutes after last daily dose	0 ng/mg Interval 0.0 to 0.151	—
Measurement of Dapivirine Concentrations in Rectal Mucosal Tissue Homogenates 24 hours after last daily dose	0 ng/mg Interval 0.0 to 0.0	—
Measurement of Dapivirine Concentrations in Rectal Mucosal Tissue Homogenates 48 hours after last daily dose	0 ng/mg Interval 0.0 to 0.0	—
Measurement of Dapivirine Concentrations in Rectal Mucosal Tissue Homogenates 72 hours after last daily dose	0 ng/mg Interval 0.0 to 0.0	—

PRIMARY outcome

Timeframe: From samples collected 24 hours after first dose to 72 hours after last daily dose

Population: enrolled participants on the Dapivirine gel arm who received at least one dose of study product. One participant with a negative estimate for the elimination rate due to an increasing trend in their concentration after multiple dosing and one participant with no values above the limit of quantification were excluded.

The terminal half-life of dapivirine in plasma samples was estimated by fitting a linear regression on the log-transformed concentrations from the 24, 48 and 72 hour time-points after the single and multiple doses.Each regression model includes an adjustment for the difference in concentration after multiple dosing. For each participant, Beta was calculated as the negative of the slope of their repression and half-life was log(2)/Beta. Due to the large number of concentrations below the limit of quantification after the single dose, the estimateion of Beta and half-life relied only on concentration after the multiple dosing for most of the participants.

Outcome measures

Outcome measures
Measure	Dapivirine Gel n=16 Participants Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic. Dapivirine gel: Dapivirine gel (0.05%); administered rectally	Placebo Gel Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic. Placebo gel: Universal HEC placebo gel; administered rectally
Terminal Half-life of Dapivirine Concentrations in Plasma	52.6 hours Interval 35.3 to 86.2	—

SECONDARY outcome

Timeframe: after completing the study (study day 40)

Population: All enrolled participants who completed the exit behavioral questionnaire.

The number of participants who responded by questionnaire that the study product was easy or very easy to use.

Outcome measures

Outcome measures
Measure	Dapivirine Gel n=17 Participants Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic. Dapivirine gel: Dapivirine gel (0.05%); administered rectally	Placebo Gel n=9 Participants Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic. Placebo gel: Universal HEC placebo gel; administered rectally
Acceptability: Ease of Use	16 Participants	9 Participants

SECONDARY outcome

Timeframe: after completing the study (study day 40)

The number of participants who responded on a questionnaire that the study product was comfortable or very comfortable.

Outcome measures

Outcome measures
Measure	Dapivirine Gel n=17 Participants Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic. Dapivirine gel: Dapivirine gel (0.05%); administered rectally	Placebo Gel n=9 Participants Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic. Placebo gel: Universal HEC placebo gel; administered rectally
Acceptability: Comfort	15 Participants	7 Participants

Adverse Events

Dapivirine Gel

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo Gel

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Ross D. Cranston

Fundacio Lluita Contra la Sida, Hospital Universitari Germans Trias | Pujol

Phone: 34-934-657-897

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Dapivirine Gel n=18 participants at risk Participants will receive a single dose of dapivirine gel rectally, followed by 7 daily doses of dapivirine gel to be administered under direct observation in the clinic. Dapivirine gel: Dapivirine gel (0.05%); administered rectally	Placebo Gel n=9 participants at risk Participants will receive a single dose of placebo gel rectally, followed by 7 daily doses of placebo gel to be administered under direct observation in the clinic. Placebo gel: Universal HEC placebo gel; administered rectally
Gastrointestinal disorders Anal pruritus	5.6% 1/18 • Number of events 1 • Adverse event data was collected through study completion (between 40 to 86 days).	0.00% 0/9 • Adverse event data was collected through study completion (between 40 to 86 days).
Gastrointestinal disorders Diarrhoea	11.1% 2/18 • Number of events 2 • Adverse event data was collected through study completion (between 40 to 86 days).	22.2% 2/9 • Number of events 2 • Adverse event data was collected through study completion (between 40 to 86 days).
Gastrointestinal disorders Dyschezia	0.00% 0/18 • Adverse event data was collected through study completion (between 40 to 86 days).	11.1% 1/9 • Number of events 1 • Adverse event data was collected through study completion (between 40 to 86 days).
Gastrointestinal disorders Gastritis	0.00% 0/18 • Adverse event data was collected through study completion (between 40 to 86 days).	11.1% 1/9 • Number of events 1 • Adverse event data was collected through study completion (between 40 to 86 days).
Gastrointestinal disorders Haematochezia	5.6% 1/18 • Number of events 1 • Adverse event data was collected through study completion (between 40 to 86 days).	0.00% 0/9 • Adverse event data was collected through study completion (between 40 to 86 days).
Gastrointestinal disorders Nausea	0.00% 0/18 • Adverse event data was collected through study completion (between 40 to 86 days).	11.1% 1/9 • Number of events 1 • Adverse event data was collected through study completion (between 40 to 86 days).
Gastrointestinal disorders Proctalgia	0.00% 0/18 • Adverse event data was collected through study completion (between 40 to 86 days).	11.1% 1/9 • Number of events 1 • Adverse event data was collected through study completion (between 40 to 86 days).
Gastrointestinal disorders Vomiting	0.00% 0/18 • Adverse event data was collected through study completion (between 40 to 86 days).	11.1% 1/9 • Number of events 1 • Adverse event data was collected through study completion (between 40 to 86 days).
General disorders Malaise	0.00% 0/18 • Adverse event data was collected through study completion (between 40 to 86 days).	11.1% 1/9 • Number of events 2 • Adverse event data was collected through study completion (between 40 to 86 days).
Infections and infestations Respiratory tract infection viral	0.00% 0/18 • Adverse event data was collected through study completion (between 40 to 86 days).	11.1% 1/9 • Number of events 1 • Adverse event data was collected through study completion (between 40 to 86 days).
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/18 • Adverse event data was collected through study completion (between 40 to 86 days).	11.1% 1/9 • Number of events 1 • Adverse event data was collected through study completion (between 40 to 86 days).
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/18 • Adverse event data was collected through study completion (between 40 to 86 days).	11.1% 1/9 • Number of events 1 • Adverse event data was collected through study completion (between 40 to 86 days).
Injury, poisoning and procedural complications procedural pain	0.00% 0/18 • Adverse event data was collected through study completion (between 40 to 86 days).	11.1% 1/9 • Number of events 1 • Adverse event data was collected through study completion (between 40 to 86 days).
Investigations blood pressure increased	5.6% 1/18 • Number of events 2 • Adverse event data was collected through study completion (between 40 to 86 days).	0.00% 0/9 • Adverse event data was collected through study completion (between 40 to 86 days).
Musculoskeletal and connective tissue disorders coccydynia	0.00% 0/18 • Adverse event data was collected through study completion (between 40 to 86 days).	11.1% 1/9 • Number of events 1 • Adverse event data was collected through study completion (between 40 to 86 days).
Nervous system disorders Headache	0.00% 0/18 • Adverse event data was collected through study completion (between 40 to 86 days).	22.2% 2/9 • Number of events 2 • Adverse event data was collected through study completion (between 40 to 86 days).
Psychiatric disorders Insomnia	11.1% 2/18 • Number of events 2 • Adverse event data was collected through study completion (between 40 to 86 days).	0.00% 0/9 • Adverse event data was collected through study completion (between 40 to 86 days).
Renal and urinary disorders Dysuria	0.00% 0/18 • Adverse event data was collected through study completion (between 40 to 86 days).	11.1% 1/9 • Number of events 1 • Adverse event data was collected through study completion (between 40 to 86 days).
Renal and urinary disorders Pollakiuria	0.00% 0/18 • Adverse event data was collected through study completion (between 40 to 86 days).	11.1% 1/9 • Number of events 1 • Adverse event data was collected through study completion (between 40 to 86 days).
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/18 • Adverse event data was collected through study completion (between 40 to 86 days).	11.1% 1/9 • Number of events 1 • Adverse event data was collected through study completion (between 40 to 86 days).
Reproductive system and breast disorders Oropharyngeal pain	5.6% 1/18 • Number of events 1 • Adverse event data was collected through study completion (between 40 to 86 days).	0.00% 0/9 • Adverse event data was collected through study completion (between 40 to 86 days).
Respiratory, thoracic and mediastinal disorders Upper-airway cough syndrome	5.6% 1/18 • Number of events 1 • Adverse event data was collected through study completion (between 40 to 86 days).	0.00% 0/9 • Adverse event data was collected through study completion (between 40 to 86 days).
Skin and subcutaneous tissue disorders Erythema	5.6% 1/18 • Number of events 1 • Adverse event data was collected through study completion (between 40 to 86 days).	0.00% 0/9 • Adverse event data was collected through study completion (between 40 to 86 days).