Clinical Trial Results:
A Phase 2, Open-label, Single-arm, Multicenter Study to Evaluate the Pharmacokinetics, Safety, Tolerability, and Efficacy of Switching to RPV Plus Other ARVs in HIV-1-infected Children (Aged 2 to <12 years) who are Virologically Suppressed
|
Summary
|
|
EudraCT number |
2018-004301-32 |
Trial protocol |
ES PT IT Outside EU/EEA RO |
Global end of trial date |
23 Feb 2023
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
07 Sep 2023
|
First version publication date |
07 Sep 2023
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
TMC278HTX2002
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT04012931 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Janssen Research & Development, LLC
|
||
Sponsor organisation address |
Turnhoutseweg 30, Beerse, Belgium, B-2340
|
||
Public contact |
Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
|
||
Scientific contact |
Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
|
||
EMA paediatric investigation plan number(s) |
EMEA-000317-PIP01-08 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
23 Feb 2023
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
23 Feb 2023
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The main objective of the trial was to evaluate the steady state pharmacokinetics (PK) of rilpivirine (RPV) and determine the appropriate dose of RPV in combination with other anti-retrovirals (ARVs) in subjects aged greater than or equal to (>=) 2 and less than (<) 12 years; and the safety and tolerability of RPV in combination with other ARVs in subjects of same age group over a 48-week treatment period.
|
||
Protection of trial subjects |
This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practice and applicable regulatory requirements.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
23 Jul 2019
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Spain: 3
|
||
Country: Number of subjects enrolled |
Italy: 5
|
||
Country: Number of subjects enrolled |
Portugal: 1
|
||
Country: Number of subjects enrolled |
Thailand: 7
|
||
Country: Number of subjects enrolled |
Uganda: 2
|
||
Country: Number of subjects enrolled |
South Africa: 8
|
||
Worldwide total number of subjects |
26
|
||
EEA total number of subjects |
9
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
26
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
||||||||||
|
Recruitment
|
||||||||||
Recruitment details |
- | |||||||||
|
Pre-assignment
|
||||||||||
Screening details |
A total of 26 subjects were enrolled and treated. | |||||||||
|
Period 1
|
||||||||||
Period 1 title |
Overall Study (overall period)
|
|||||||||
Is this the baseline period? |
Yes | |||||||||
Allocation method |
Non-randomised - controlled
|
|||||||||
Blinding used |
Not blinded | |||||||||
|
Arms
|
||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||
|
Arm title
|
Rilpivirine: >=2 to <6 Years | |||||||||
Arm description |
Subjects weighed <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 an 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. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Rilpivirine
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
EDURANT
|
|||||||||
Pharmaceutical forms |
Tablet
|
|||||||||
Routes of administration |
Oral use
|
|||||||||
Dosage and administration details |
Subjects weighed <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 an 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.
|
|||||||||
Investigational medicinal product name |
Antiretrovirals
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||
Routes of administration |
Oral use
|
|||||||||
Dosage and administration details |
Subjects received investigator-selected antiretrovirals, including but not limited to 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.
|
|||||||||
|
Arm title
|
Rilpivirine: >=6 to <12 years | |||||||||
Arm description |
Subjects weighed <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 an 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. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Antiretrovirals
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||
Routes of administration |
Oral use
|
|||||||||
Dosage and administration details |
Subjects received investigator-selected antiretrovirals, including but not limited to N(t)RTIs (example, AZT, ABC, TAF, or TDF in combination with FTC or 3TC), whichever were approved and marketed or considered local standard of care for children aged between 2 and < 12 years in a particular country.
|
|||||||||
Investigational medicinal product name |
Rilpivirine
|
|||||||||
Investigational medicinal product code |
||||||||||
Other name |
EDURANT
|
|||||||||
Pharmaceutical forms |
Tablet
|
|||||||||
Routes of administration |
Oral use
|
|||||||||
Dosage and administration details |
Subjects weighed <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 an 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.
|
|||||||||
|
||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rilpivirine: >=2 to <6 Years
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects weighed <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 an 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rilpivirine: >=6 to <12 years
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects weighed <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 an 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Rilpivirine: >=2 to <6 Years
|
||
Reporting group description |
Subjects weighed <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 an 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. | ||
Reporting group title |
Rilpivirine: >=6 to <12 years
|
||
Reporting group description |
Subjects weighed <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 an 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. | ||
Subject analysis set title |
Rilpivirine 12.5 Milligrams (mg) (<20 kg)
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Subjects weighed less than (<)20 kilograms (kg) received rilpivirine 12.5 mg orally once daily in combination with an 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.
|
||
Subject analysis set title |
Rilpivirine 15 mg (<20 kg)
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Subjects weighed <20 kg received rilpivirine 15 mg orally once daily in combination with an 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.
|
||
Subject analysis set title |
Rilpivirine 15 mg (20 to <25 kg)
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Subjects weighed 20 to <25 kg received rilpivirine 15 mg orally once daily in combination with an 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.
|
||
Subject analysis set title |
Rilpivirine 25 mg (>=25 kg)
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Subjects weighed >=25 kg received rilpivirine 25 mg orally once daily in combination with an 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.
|
||
|
|||||||||||||||||||||
End point title |
Area Under the Plasma Concentration-time Curve from Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine [1] | ||||||||||||||||||||
End point 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. Full analysis set (FAS) included all subjects who had taken at least 1 dose of rilpivirine, regardless of their compliance with the protocol and adherence to the dosing regimen. Here, 'N' (number of subjects analysed) signifies subjects who were evaluable for this endpoint. Here, '99999' signifies that reported data were individual data, hence mean and standard deviation was not evaluable. One subject with body weight <20 kg who was on 12.5 mg rilpivirine did not increase the rilpivirine dose upon increase in body weight to 20.5 kg at Week 24. This subject switched to the 15 mg dose approximately 1 week before the Week 40 visit.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Predose up to 24 hours postdose
|
||||||||||||||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics was done, no inferential statistical analysis was performed. |
|||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Percentage of Subjects with HIV-1 Ribonucleic Acid (RNA) <50 and >=50 Copies/mL Through Weeks 24 and 48 | ||||||||||||||||||||||||
End point description |
Percentage of subjects with a HIV-1 RNA <50 copies per mL and >=50 copies/mL were assessed using FDA snapshot approach which defines a subject'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.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Up to Weeks 24 and 48
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Percentage of Subjects with HIV-1 Ribonucleic Acid (RNA) <400 and >=400 Copies/mL Through Weeks 24 and 48 | ||||||||||||||||||||||||
End point description |
Percentage of subjects with viral load (plasma HIV-1 RNA levels) less than (<) 400 copies/mL and >=400 copies/mL measured by the Food and Drug Administration (FDA) snapshot algorithm were reported. The FDA snapshot analysis was Week 24 and Week 48 based on the last observed plasma viral load data within the visit window (that is, Weeks 24 and 48). FAS included all subjects who had taken at least 1 dose of rilpivirine.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Up to Weeks 24 and 48
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||
End point title |
Change from Baseline in Cluster Differentiation 4 (CD4+) Cell Count up to Week 24 and Week 48 | ||||||||||||||||||
End point description |
The immunologic change was determined by changes in Cluster of CD4+ cell count using non-completer = failure imputation, that is discontinuation were imputed with baseline value resulting in change=0, other missing data using last observation carried forward (LOCF). FAS included all subjects who had taken at least 1 dose of rilpivirine. Here, 99999 reported since SD was not evaluable for 1 subject.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
From baseline up to Weeks 24 and 48
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Predose Plasma Concentration (C0h) of Rilpivirine | ||||||||||||||||||||
End point description |
C0h was defined as the predose plasma concentration of rilpivirine. FAS included all subjects who had taken at least 1 dose of rilpivirine, regardless of their compliance with the protocol and adherence to the dosing regimen. Here, 'N' (number of subjects analysed) signifies subjects who were evaluable for this endpoint. Here, '99999' signifies that reported data were individual data, hence mean and standard deviation was not evaluable. One subject with body weight <20 kg who was on 12.5 mg rilpivirine did not increase the rilpivirine dose upon increase in body weight to 20.5 kg at Week 24. This subject switched to the 15 mg dose approximately 1 week before the Week 40 visit.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Predose (Day 0)
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Maximum Observed Plasma Concentration (Cmax) of Rilpivirine | ||||||||||||||||||||
End point description |
Cmax was defined as the maximum observed plasma concentration of rilpivirine. FAS included all subjects who had taken at least 1 dose of rilpivirine, regardless of their compliance with the protocol and adherence to the dosing regimen. Here, 'N' (number of subjects analysed) signifies subjects who were evaluable for this endpoint. Here, '99999' signifies that reported data were individual data, hence mean and standard deviation was not evaluable. One subject with body weight <20 kg who was on 12.5 mg rilpivirine did not increase the rilpivirine dose upon increase in body weight to 20.5 kg at Week 24. This subject switched to the 15 mg dose approximately 1 week before the Week 40 visit.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Predose up to 24 hours postdose
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Percentage of Subjects with Viral Genotype at the Time of Virologic Failure at Weeks 24 and 48 | ||||||||||||||||||||||||
End point description |
Percentage of subjects with viral genotype at the time of virologic failure (that is, HIV 1 RNA >=50 and >=400 copies/mL) per 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. FAS included all subjects who had taken at least 1 dose of rilpivirine.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Weeks 24 and 48
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||
End point title |
Percentage of Subjects with Treatment Adherence >95% Based on Tablet Count up to Weeks 24 and 48 | ||||||||||||||||||
End point description |
Percentage of subjects with treatment adherence >95 % 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 greater than (>) 95 percent (%) by tablet count. FAS included all subjects who had taken at least 1 dose of rilpivirine.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Up to Weeks 24 and 48
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to Week 48
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
FAS included all subjects who had taken at least 1 dose of rilpivirine.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rilpivirine
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
FAS included all subjects who had taken at least 1 dose of rilpivirine. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
24 Apr 2019 |
The purpose of the this amendment was to remove inclusion criteria 5 stating that
subjects needed to be aware of their human immunodeficiency virus-1 diagnosis. |
||
18 Dec 2019 |
The purpose of this amendment was to include that rilpivirine dose selection should be based on the subject’s body weight at baseline. Children with a body weight of <25 kg should be dosed with rilpivirine 15 mg once daily and children with a body weight of greater than or equal to (>=)25 kg should be dosed with rilpivirine 25 mg once daily. |
||
21 Feb 2021 |
The purpose of this amendment was to include an optional intensive pharmacokinetic (PK) substudy at several study sites and to clarify some of the inclusion and exclusion criteria. Rilpivirine dose for subjects with a body weight less than (<)20 killograms (kg) was amended from 15 milligrams (mg) to 12.5 mg once daily. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Endpoints presented are consistent to those provided for the other pediatric study with oral rilpivirine (study TMC278-TiDP38-C213). | |||
