A Study of Switching to RPV Plus Other ARVs in HIV-1-infected Children (Aged 2 to <12 Years) Who Are Virologically Suppressed

• ClinicalTrials.gov Identifier: NCT04012931
• Recruitment Status: Completed
• First Posted: July 9, 2019
• Results First Posted: May 2, 2024
• Last Update Posted: May 2, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV
• Interventions: Drug: Rilpivirine; Drug: ARV Background Regimen
• Enrollment: 26

Participant Flow

Recruitment Details

Pre-assignment Details

Participant flow is based on the initial administered dose, irrespective of subsequent dose-alterations. Out of the 2 participants weighing <20 kg who received rilpivirine 15 mg, 1 participant switched to rilpivirine 12.5 mg group after the first 4 weeks. This participant was counted in the <20 kg rilpivirine 15 mg group in the Participant flow section, whereas it was counted in the <20 kg rilpivirine 12.5 mg group for the pharmacokinetic assessments reported in the outcome measure section.

Arm/Group Title	Rilpivirine
Arm/Group Description	Participants weighing less than (<) 20 kilograms (kg) received rilpivirine 12.5 milligrams (mg) or 15 mg; 20 to <25 kg received rilpivirine 15 mg; greater than equal to (>=) 25 kg received rilpivirine 25 mg orally once daily in combination with investigator-selected antiretrovirals (ARVs), including but not limited to nucleoside/nucleotide reverse transcriptase inhibitor (N[t]RTIs) (example, azidothymidine [AZT], abacavir [ABC], tenofovir alafenamide [TAF], or tenofovir disoproxil fumarate [TDF] in combination with emtricitabine [FTC] or lamivudine [3TC]), whichever were approved and marketed or considered local standard of care for children aged between >=2 and <12 years in a particular country. Integrase inhibitors (for example, dolutegravir [DTG] or raltegravir) were administered in combination with rilpivirine as appropriate. The overall treatment duration of the study was 52 weeks.
Period Title: Overall Study
Started	26
Participants Aged 2 to <6 Years	1
Participants Aged >=6 to <12 Years	25
Participants >=25 kg Who Received 25 mg Rilpivirine	18
Participants 20 to <25 kg Who Received 15 mg Rilpivirine	5
Participants <20 kg Who Received 15 mg Rilpivirine	2
Participants <20 kg Who Received 12.5 mg Rilpivirine	1
Completed	26
Not Completed	0

Baseline Characteristics

Arm/Group Title		Rilpivirine
Arm/Group Description		Participants weighing less than (<) 20 kilograms (kg) received rilpivirine 12.5 milligrams (mg) or 15 mg; 20 to <25 kg received rilpivirine 15 mg; greater than equal to (>=) 25 kg received rilpivirine 25 mg orally once daily in combination with investigator-selected antiretrovirals (ARVs), including but not limited to nucleoside/nucleotide reverse transcriptase inhibitor (N[t]RTIs) (example, azidothymidine [AZT], abacavir [ABC], tenofovir alafenamide [TAF], or tenofovir disoproxil fumarate [TDF] in combination with emtricitabine [FTC] or lamivudine [3TC]), whichever were approved and marketed or considered local standard of care for children aged between >=2 and <12 years in a particular country. Integrase inhibitors (for example, dolutegravir [DTG] or raltegravir) were administered in combination with rilpivirine as appropriate. The overall treatment duration of the study was 52 weeks.
Overall Number of Baseline Participants		26
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	26 participants
		9.5 (1.83)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants
	Children (2-12 years)	26 100.0%
	Adolescents (12-17 years)	0 0.0%
	Adults (18-64 years)	0 0.0%
	From 65 to 84 years	0 0.0%
	85 years and over	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants
	Female	10 38.5%
	Male	16 61.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants
	Hispanic or Latino	4 15.4%
	Not Hispanic or Latino	22 84.6%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants
	American Indian or Alaska Native	0 0.0%
	Asian	7 26.9%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	13 50.0%
	White	6 23.1%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	26 participants
Italy		5 19.2%
Portugal		1 3.8%
South Africa		8 30.8%
Spain		3 11.5%
Thailand		7 26.9%
Uganda		2 7.7%

Outcome Measures

1. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 12.5 mg (for <20 kg Group)
Description	AUC(0-24h) was defined the area under the plasma concentration-time curve from time of administration up to 24 hours postdose of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. Out of the 2 participants weighing <20 kg who received rilpivirine 15 mg, 1 participant switched to rilpivirine 12.5 mg group after the first 4 weeks. This participant was counted in the <20 kg rilpivirine 12.5 mg group for the pharmacokinetic assessments, hence the number of participants analyzed for this outcome measure in this arm are exceeding the participants that started this arm. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time Frame	Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS): who had taken at least 1 dose of rilpivirine. N (number of participants analyzed): who were evaluable for this outcome measure, intensive PK data was collected from a subset of participants.

Arm/Group Title		Rilpivirine 12.5 Milligrams (mg) (<20 kg)
Arm/Group Description:		Participants weighing less than (<)20 kilograms (kg) received rilpivirine 12.5 mg orally once daily in combination with investigator-selected background regimen, that were approved and marketed or considered local standard of care for children aged between 2 and 12 years in a particular country.
Overall Number of Participants Analyzed		2
Mean (Standard Deviation); Unit of Measure: nanograms*hour/milliliter (ng*h/mL)
Participant 1	Number Analyzed	1 participants
		4116 [1] (NA)
Participant 2	Number Analyzed	1 participants
		4646 [1] (NA)

[1]

Standard deviation could not be calculated for a single participant.

2. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 15 mg (for <20 kg Group)
Description	AUC(0-24h) was defined the area under the plasma concentration-time curve from time of administration up to 24 hours postdose of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time Frame	Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)

Outcome Measure Data

Analysis Population Description

FAS included all participants who had taken at least 1 dose of rilpivirine. N (number of participants analyzed): who were evaluable for this outcome measure, intensive PK data was collected from a subset of participants.

Arm/Group Title	Rilpivirine 15 mg (<20 kg)
Arm/Group Description:	Participants weighing <20 kg received rilpivirine 15 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between 2 and 12 years in a particular country.
Overall Number of Participants Analyzed	1
Mean (Standard Deviation); Unit of Measure: ng*h/mL
	3494 [1] (NA)

[1]

Standard deviation could not be calculated for a single participant.

3. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 15 mg (for 20 to <25 mg Group)
Description	AUC(0-24h) was defined the area under the plasma concentration-time curve from time of administration up to 24 hours postdose of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time Frame	Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)

Outcome Measure Data

Analysis Population Description

FAS included all participants who had taken at least 1 dose of rilpivirine.

Arm/Group Title	Rilpivirine 15 mg (20 to <25 kg)
Arm/Group Description:	Participants weighing 20 to <25 kg received rilpivirine 15 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between 2 and 12 years in a particular country.
Overall Number of Participants Analyzed	5
Mean (Standard Deviation); Unit of Measure: ng*h/mL
	3506 (946)

4. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 25 mg (for >=25 kg Group)
Description	AUC(0-24h) was defined the area under the plasma concentration-time curve from time of administration up to 24 hours postdose of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time Frame	Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)

Outcome Measure Data

Analysis Population Description

FAS included all participants who had taken at least 1 dose of rilpivirine. N (number of participants analyzed): who were evaluable for this outcome measure, intensive PK data was collected from a subset of participants.

Arm/Group Title		Rilpivirine 25 mg (>=25 kg)
Arm/Group Description:		Participants weighing >=25 kg received rilpivirine 25 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between 2 and 12 years in a particular country.
Overall Number of Participants Analyzed		2
Mean (Standard Deviation); Unit of Measure: ng*h/mL
Participant 1	Number Analyzed	1 participants
		4514 [1] (NA)
Participant 2	Number Analyzed	1 participants
		5644 [1] (NA)

[1]

Standard deviation could not be calculated for a single participant.

5. Secondary Outcome

Title	Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 and >=50 Copies/mL Through Weeks 24 and 48
Description	Percentage of participants with a HIV-1 RNA less than (<) 50 copies per mL and greater than or equal to (>=)50 copies/mL were assessed using Food and Drug Administration (FDA) snapshot approach which defines a participant's virologic response status using only the viral load at the predefined time point within a window of time, along with study drug discontinuation status. HIV-1 RNA level <50 copies per mL, was considered as virologic success and >= 50 copies/mL was considered as virological failure as per the snapshot approach. The FDA snapshot analysis at Week 24 and Week 48 was based on the last observed plasma viral load data within the visit window (that is, Weeks 24 and 48).
Time Frame	From Day 1 up to Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

FAS included all participants who had taken at least 1 dose of rilpivirine.

Arm/Group Title	Rilpivirine: >=2 to <6 Years	Rilpivirine: >=6 to <12 Years
Arm/Group Description:	Participants weighing <20 kilograms (kg) received rilpivirine 12.5 milligrams (mg) or 15 mg; 20-<25 kg received 15 mg; >=25 kg received 25 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between >=2 and <6 years in a particular country. Integrase inhibitors (for example, dolutegravir [DTG] or raltegravir) could also be administered in combination with rilpivirine as appropriate.	Participants weighing <20 kg received rilpivirine 12.5 mg or 15 mg; 20-<25 kg received 15 mg; >=25 kg received 25 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between >=6 and <12 years in a particular country. Integrase inhibitors (for example, dolutegravir [DTG] or raltegravir) could also be administered in combination with rilpivirine as appropriate.
Overall Number of Participants Analyzed	1	25
Measure Type: Number; Unit of Measure: Percentage of participants
Week 24: <50 copies/mL	100.0	100.0
Week 24: >=50 copies/mL	0.0	0.0
Week 48: <50 copies/mL	100.0	100.0
Week 48: >=50 copies/mL	0.0	0.0

6. Secondary Outcome

Title	Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <400 and >=400 Copies/mL Through Weeks 24 and 48
Description	Percentage of participants with viral load (plasma HIV-1 RNA levels) <400 copies/mL and >=400 copies/mL were assessed by the FDA snapshot approach which defines a participant's virologic response status using only the viral load at the predefined time point within a window of time, along with study drug discontinuation status. HIV-1 RNA level <400 copies per mL, was considered as virologic success and >=400 copies/mL was considered as virological failure as per the snapshot approach. The FDA snapshot analysis at Week 24 and Week 48 was based on the last observed plasma viral load data within the visit window (that is, Weeks 24 and 48).
Time Frame	From Day 1 up to Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

FAS included all participants who had taken at least 1 dose of rilpivirine.

Arm/Group Title	Rilpivirine: >=2 to <6 Years	Rilpivirine: >=6 to <12 Years
Arm/Group Description:	Participants weighing <20 kilograms (kg) received rilpivirine 12.5 milligrams (mg) or 15 mg; 20-<25 kg received 15 mg; >=25 kg received 25 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between >=2 and <6 years in a particular country. Integrase inhibitors (for example, dolutegravir [DTG] or raltegravir) could also be administered in combination with rilpivirine as appropriate.	Participants weighing <20 kg received rilpivirine 12.5 mg or 15 mg; 20-<25 kg received 15 mg; >=25 kg received 25 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between >=6 and <12 years in a particular country. Integrase inhibitors (for example, dolutegravir [DTG] or raltegravir) could also be administered in combination with rilpivirine as appropriate.
Overall Number of Participants Analyzed	1	25
Measure Type: Number; Unit of Measure: Percentage of participants
Week 24: <400 copies/mL	100.0	100.0
Week 24: >=400 copies/mL	0.0	0.0
Week 48: <400 copies/mL	100.0	100.0
Week 48: >=400 copies/mL	0.0	0.0

7. Secondary Outcome

Title	Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count up to Week 24 and Week 48
Description	The immunologic change was determined by changes in CD4+ cell count using non-completer = failure imputation, that was, missing values after discontinuation were imputed with the baseline value, thus resulting in a 0 change. For intermittent missing data, last observation carried forward (LOCF) approach was applied.
Time Frame	From baseline (Day 1) up to Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

FAS included all participants who had taken at least 1 dose of rilpivirine.

Arm/Group Title	Rilpivirine: >=2 to <6 Years	Rilpivirine: >=6 to <12 Years
Arm/Group Description:	Participants weighing <20 kilograms (kg) received rilpivirine 12.5 milligrams (mg) or 15 mg; 20-<25 kg received 15 mg; >=25 kg received 25 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between >=2 and <6 years in a particular country. Integrase inhibitors (for example, dolutegravir [DTG] or raltegravir) could also be administered in combination with rilpivirine as appropriate.	Participants weighing <20 kg received rilpivirine 12.5 mg or 15 mg; 20-<25 kg received 15 mg; >=25 kg received 25 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between >=6 and <12 years in a particular country. Integrase inhibitors (for example, dolutegravir [DTG] or raltegravir) could also be administered in combination with rilpivirine as appropriate.
Overall Number of Participants Analyzed	1	25
Mean (Standard Error); Unit of Measure: Cells/cubic millimeter
Week 24	313.0 [1] (NA)	26.3 (32.10)
Week 48	279.0 [1] (NA)	-19.9 (28.52)

[1]

Standard error could not be calculated for a single participant.

8. Secondary Outcome

Title	Predose Plasma Concentration (C[0h]) of Rilpivirine 12.5 mg (for <20 kg Group)
Description	C(0h) was defined as the predose plasma concentration of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. Out of the 2 participants weighing <20 kg who received rilpivirine 15 mg, 1 participant switched to rilpivirine 12.5 mg group after the first 4 weeks. This participant was counted in the <20 kg rilpivirine 12.5 mg group for the pharmacokinetic assessments, hence the number of participants analyzed for this outcome measure in this arm are exceeding the participants that started this arm. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time Frame	Predose at anytime during Day 28 to Day 32 (Week 4)

Outcome Measure Data

Analysis Population Description

FAS included all participants who had taken at least 1 dose of rilpivirine. N (number of participants analyzed): who were evaluable for this outcome measure, intensive PK data was collected from a subset of participants.

Arm/Group Title		Rilpivirine 12.5 Milligrams (mg) (<20 kg)
Arm/Group Description:		Participants weighing less than (<)20 kilograms (kg) received rilpivirine 12.5 mg orally once daily in combination with investigator-selected background regimen, that were approved and marketed or considered local standard of care for children aged between 2 and 12 years in a particular country.
Overall Number of Participants Analyzed		2
Mean (Standard Deviation); Unit of Measure: ng/mL
Participant 1	Number Analyzed	1 participants
		116 [1] (NA)
Participant 2	Number Analyzed	1 participants
		161 [1] (NA)

[1]

Standard deviation could not be calculated for a single participant.

9. Secondary Outcome

Title	Predose Plasma Concentration (C[0h]) of Rilpivirine 15 mg (for <20 kg Group)
Description	C(0h) was defined as the predose plasma concentration of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time Frame	Predose at anytime during Day 28 to Day 32 (Week 4)

Outcome Measure Data

Analysis Population Description

FAS included all participants who had taken at least 1 dose of rilpivirine. N (number of participants analyzed): who were evaluable for this outcome measure, intensive PK data was collected from a subset of participants.

Arm/Group Title	Rilpivirine 15 mg (<20 kg)
Arm/Group Description:	Participants weighing <20 kg received rilpivirine 15 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between 2 and 12 years in a particular country.
Overall Number of Participants Analyzed	1
Mean (Standard Deviation); Unit of Measure: ng/mL
	79.3 [1] (NA)

[1]

Standard deviation could not be calculated for a single participant.

10. Secondary Outcome

Title	Predose Plasma Concentration (C[0h]) of Rilpivirine 15 mg (for 20 to <25 kg Group)
Description	C(0h) was defined as the predose plasma concentration of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time Frame	Predose at anytime during Day 28 to Day 32 (Week 4)

Outcome Measure Data

Analysis Population Description

FAS included all participants who had taken at least 1 dose of rilpivirine.

Arm/Group Title	Rilpivirine 15 mg (20 to <25 kg)
Arm/Group Description:	Participants weighing 20 to <25 kg received rilpivirine 15 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between 2 and 12 years in a particular country.
Overall Number of Participants Analyzed	5
Mean (Standard Deviation); Unit of Measure: ng/mL
	138 (58.7)

11. Secondary Outcome

Title	Predose Plasma Concentration (C[0h]) of Rilpivirine 25 mg (for >=25 kg Group)
Description	C(0h) was defined as the predose plasma concentration of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time Frame	Predose at anytime during Day 28 to Day 32 (Week 4)

Outcome Measure Data

Analysis Population Description

FAS included all participants who had taken at least 1 dose of rilpivirine. N (number of participants analyzed): who were evaluable for this outcome measure, intensive PK data was collected from a subset of participants.

Arm/Group Title		Rilpivirine 25 mg (>=25 kg)
Arm/Group Description:		Participants weighing >=25 kg received rilpivirine 25 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between 2 and 12 years in a particular country.
Overall Number of Participants Analyzed		2
Mean (Standard Deviation); Unit of Measure: ng/mL
Participant 1	Number Analyzed	1 participants
		146 [1] (NA)
Participant 2	Number Analyzed	1 participants
		342 [1] (NA)

[1]

Standard deviation could not be calculated for a single participant.

12. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 12.5 mg (for <20 kg Group)
Description	Cmax was defined as the maximum observed plasma concentration of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. Out of the 2 participants weighing <20 kg who received rilpivirine 15 mg, 1 participant switched to rilpivirine 12.5 mg group after the first 4 weeks. This participant was counted in the <20 kg rilpivirine 12.5 mg group for the pharmacokinetic assessments, hence the number of participants analyzed for this outcome measure in this arm are exceeding the participants that started this arm. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time Frame	Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)

Outcome Measure Data

Analysis Population Description

FAS included all participants who had taken at least 1 dose of rilpivirine. N (number of participants analyzed): who were evaluable for this outcome measure, intensive PK data was collected from a subset of participants.

Arm/Group Title		Rilpivirine 12.5 Milligrams (mg) (<20 kg)
Arm/Group Description:		Participants weighing less than (<)20 kilograms (kg) received rilpivirine 12.5 mg orally once daily in combination with investigator-selected background regimen, that were approved and marketed or considered local standard of care for children aged between 2 and 12 years in a particular country.
Overall Number of Participants Analyzed		2
Mean (Standard Deviation); Unit of Measure: ng/mL
Participant 1	Number Analyzed	1 participants
		273 [1] (NA)
Participant 2	Number Analyzed	1 participants
		318 [1] (NA)

[1]

Standard deviation could not be calculated for a single participant.

13. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 15 mg (for <20 kg Group)
Description	Cmax was defined as the maximum observed plasma concentration of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time Frame	Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)

Outcome Measure Data

Analysis Population Description

FAS included all participants who had taken at least 1 dose of rilpivirine. N (number of participants analyzed): who were evaluable for this outcome measure, intensive PK data was collected from a subset of participants.

Arm/Group Title	Rilpivirine 15 mg (<20 kg)
Arm/Group Description:	Participants weighing <20 kg received rilpivirine 15 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between 2 and 12 years in a particular country.
Overall Number of Participants Analyzed	1
Mean (Standard Deviation); Unit of Measure: ng/mL
	214 [1] (NA)

[1]

Standard deviation could not be calculated for a single participant.

14. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 15 mg (for 20 to <25 mg Group)
Description	Cmax was defined as the maximum observed plasma concentration of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time Frame	Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)

Outcome Measure Data

Analysis Population Description

FAS included all participants who had taken at least 1 dose of rilpivirine.

Arm/Group Title	Rilpivirine 15 mg (20 to <25 kg)
Arm/Group Description:	Participants weighing 20 to <25 kg received rilpivirine 15 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between 2 and 12 years in a particular country.
Overall Number of Participants Analyzed	5
Mean (Standard Deviation); Unit of Measure: ng/mL
	217 (43.1)

15. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 25 mg (for >=25 kg Group)
Description	Cmax was defined as the maximum observed plasma concentration of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time Frame	Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)

Outcome Measure Data

Analysis Population Description

FAS included all participants who had taken at least 1 dose of rilpivirine. N (number of participants analyzed): who were evaluable for this outcome measure, intensive PK data was collected from a subset of participants.

Arm/Group Title		Rilpivirine 25 mg (>=25 kg)
Arm/Group Description:		Participants weighing >=25 kg received rilpivirine 25 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between 2 and 12 years in a particular country.
Overall Number of Participants Analyzed		2
Mean (Standard Deviation); Unit of Measure: ng/mL
Participant 1	Number Analyzed	1 participants
		309 [1] (NA)
Participant 2	Number Analyzed	1 participants
		418 [1] (NA)

[1]

Standard deviation could not be calculated for a single participant.

16. Secondary Outcome

Title	Percentage of Participants With Viral Genotype at the Time of Virologic Failure at Weeks 24 and 48
Description	Percentage of participants with viral genotype at the time of virologic failure (that is, HIV 1 RNA >=50 copies/mL and >=400 copies/mL) per FDA snapshot approach were reported. Confirmed virologic failure was defined as 2 consecutive HIV-1 RNA plasma viral load measurements >=200 copies/mL and suspected virologic failure was defined as HIV-1 RNA >=200 copies/mL. No participant achieved virologic failure hence this outcome measure could not be evaluated.
Time Frame	Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

FAS included all participants who had taken at least 1 dose of rilpivirine.

Arm/Group Title	Rilpivirine: >=2 to <6 Years	Rilpivirine: >=6 to <12 Years
Arm/Group Description:	Participants weighing <20 kilograms (kg) received rilpivirine 12.5 milligrams (mg) or 15 mg; 20-<25 kg received 15 mg; >=25 kg received 25 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between >=2 and <6 years in a particular country. Integrase inhibitors (for example, dolutegravir [DTG] or raltegravir) could also be administered in combination with rilpivirine as appropriate.	Participants weighing <20 kg received rilpivirine 12.5 mg or 15 mg; 20-<25 kg received 15 mg; >=25 kg received 25 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between >=6 and <12 years in a particular country. Integrase inhibitors (for example, dolutegravir [DTG] or raltegravir) could also be administered in combination with rilpivirine as appropriate.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

17. Secondary Outcome

Title	Percentage of Participants With Treatment Adherence >95% Based on Tablet Count up to Weeks 24 and 48
Description	Percentage of participants with treatment adherence greater than (>) 95 percent (%) as assessed by tablet count (study intervention accountability) up to Weeks 24 and 48 of study treatment were reported. Treatment adherence was defined as having a treatment adherence of >95% by tablet count.
Time Frame	From Day 1 up to Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

FAS included all participants who had taken at least 1 dose of rilpivirine. N (number of participants analyzed): participants who were evaluable for this outcome measure. For participants who never returned kits dispensed at baseline, adherence could not be derived.

Arm/Group Title	Rilpivirine: >=2 to <6 Years	Rilpivirine: >=6 to <12 Years
Arm/Group Description:	Participants weighing <20 kilograms (kg) received rilpivirine 12.5 milligrams (mg) or 15 mg; 20-<25 kg received 15 mg; >=25 kg received 25 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between >=2 and <6 years in a particular country. Integrase inhibitors (for example, dolutegravir [DTG] or raltegravir) could also be administered in combination with rilpivirine as appropriate.	Participants weighing <20 kg received rilpivirine 12.5 mg or 15 mg; 20-<25 kg received 15 mg; >=25 kg received 25 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between >=6 and <12 years in a particular country. Integrase inhibitors (for example, dolutegravir [DTG] or raltegravir) could also be administered in combination with rilpivirine as appropriate.
Overall Number of Participants Analyzed	1	22
Measure Type: Number; Unit of Measure: Percentage of participants
Week 24	100.0	86.4
Week 48	100.0	90.9

18. Secondary Outcome

Title	Change From Baseline in Percentage of Cluster of Differentiation 4 (CD4+) Cell Count up to Week 24 and Week 48
Description	The immunologic change was determined by changes in CD4+ cell count using non-completer = failure imputation, that was, missing values after discontinuation were imputed with the baseline value, thus resulting in a 0 change. For intermittent missing data, last observation carried forward (LOCF) approach was applied.
Time Frame	From baseline (Day 1) up to Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

FAS included all participants who had taken at least 1 dose of rilpivirine.

Arm/Group Title	Rilpivirine: >=2 to <6 Years	Rilpivirine: >=6 to <12 Years
Arm/Group Description:	Participants weighing <20 kilograms (kg) received rilpivirine 12.5 milligrams (mg) or 15 mg; 20-<25 kg received 15 mg; >=25 kg received 25 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between >=2 and <6 years in a particular country. Integrase inhibitors (for example, dolutegravir [DTG] or raltegravir) could also be administered in combination with rilpivirine as appropriate.	Participants weighing <20 kg received rilpivirine 12.5 mg or 15 mg; 20-<25 kg received 15 mg; >=25 kg received 25 mg orally once daily in combination with investigator-selected background regimen, whichever were approved and marketed or considered local standard of care for children aged between >=6 and <12 years in a particular country. Integrase inhibitors (for example, dolutegravir [DTG] or raltegravir) could also be administered in combination with rilpivirine as appropriate.
Overall Number of Participants Analyzed	1	25
Mean (Standard Error); Unit of Measure: Percentage of lymphocytes
Week 24	5.3 [1] (NA)	1.2 (1.04)
Week 48	6.4 [1] (NA)	0.7 (1.14)

[1]

Standard error could not be calculated for a single participant

Adverse Events

Time Frame	Baseline (Day 1) up to Week 52
Adverse Event Reporting Description	Safety was based on the full analysis set (FAS) which included all participants who had taken at least 1 dose of rilpivirine.
Arm/Group Title	Rilpivirine
Arm/Group Description	Participants weighing less than (<) 20 kilograms (kg) received rilpivirine 12.5 milligrams (mg) or 15 mg; 20 to <25 kg received rilpivirine 15 mg; greater than equal to (>=) 25 kg received rilpivirine 25 mg orally once daily in combination with investigator-selected antiretrovirals (ARVs), including but not limited to nucleoside/nucleotide reverse transcriptase inhibitor (N[t]RTIs) (example, azidothymidine [AZT], abacavir [ABC], tenofovir alafenamide [TAF], or tenofovir disoproxil fumarate [TDF] in combination with emtricitabine [FTC] or lamivudine [3TC]), whichever were approved and marketed or considered local standard of care for children aged between >=2 and <12 years in a particular country. Integrase inhibitors (for example, dolutegravir [DTG] or raltegravir) were administered in combination with rilpivirine as appropriate. The overall treatment duration of the study was 52 weeks.
All-Cause Mortality
	Rilpivirine
	Affected / at Risk (%)
Total	0/26 (0.00%)
Serious Adverse Events
	Rilpivirine
	Affected / at Risk (%)	# Events
Total	0/26 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Rilpivirine
	Affected / at Risk (%)	# Events
Total	11/26 (42.31%)
Gastrointestinal disorders
Abdominal Pain * 1	2/26 (7.69%)	2
Nausea * 1	2/26 (7.69%)	3
Vomiting * 1	4/26 (15.38%)	16
General disorders
Pyrexia * 1	2/26 (7.69%)	2
Infections and infestations
Rhinitis * 1	2/26 (7.69%)	3
Upper Respiratory Tract Infection * 1	2/26 (7.69%)	2
Investigations
Alanine Aminotransferase Increased * 1	3/26 (11.54%)	5
Aspartate Aminotransferase Increased * 1	2/26 (7.69%)	2
Metabolism and nutrition disorders
Decreased Appetite * 1	2/26 (7.69%)	2
Nervous system disorders
Headache * 1	2/26 (7.69%)	2
Respiratory, thoracic and mediastinal disorders
Nasal Congestion * 1	2/26 (7.69%)	2
1 Term from vocabulary, MedDRA 25.1; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent application.

Results Point of Contact

• Name/Title: Global Medical Head
• Organization: Janssen Research & Development, LLC
• Phone: 844-434-4210
• EMail: ClinicalTrialDisclosure@its.jnj.com

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT04012931
• Other Study ID Numbers: CR108606; 2018-004301-32 ( EudraCT Number ); TMC278HTX2002 ( Other Identifier: Janssen Research & Development, LLC )
• First Submitted: July 8, 2019
• First Posted: July 9, 2019
• Results First Submitted: February 16, 2024
• Results First Posted: May 2, 2024
• Last Update Posted: May 2, 2024