Clinical Trials Register

Summary
EudraCT Number:	2018-004301-32
Sponsor's Protocol Code Number:	TMC278HTX2002
National Competent Authority:	Romania - National Agency for Medicines and Medical Devices
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2022-03-31
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Romania - National Agency for Medicines and Medical Devices

A.2

EudraCT number

2018-004301-32

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Clinical 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

A.4.1

Sponsor's protocol code number

TMC278HTX2002

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/322/2018

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Janssen Sciences Ireland UC
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Janssen Sciences Ireland UC
B.4.2	Country	Ireland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janssen Research and Development
B.5.2	Functional name of contact point	Cheryll Natress
B.5.3	Address:
B.5.3.1	Street Address	50-100 Holmers Farm Way
B.5.3.2	Town/ city	High Wycombe
B.5.3.3	Post code	HP12 4DP
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	00441494658589
B.5.5	Fax number	0044203320102
B.5.6	E-mail	prderacta@prdgb.JNJ.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Edurant®
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Rilpivirine
D.3.2	Product code	TMC278
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Rilpivirine Hydrochloride
D.3.9.1	CAS number	700361-47-3
D.3.9.2	Current sponsor code	TMC278
D.3.9.3	Other descriptive name	R314585
D.3.9.4	EV Substance Code	SUB31460
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Rilpivirine hydrochloride
D.3.2	Product code	TMC278
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Rilpivirine hydrochloride
D.3.9.1	CAS number	700361-47-3
D.3.9.2	Current sponsor code	TMC278
D.3.9.3	Other descriptive name	RILPIVIRINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB31460
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

HIV-1 Infection

E.1.1.1

Medical condition in easily understood language

HIV-1 Infection

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10068341
E.1.2	Term	HIV-1 infection
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objectives are:
• To evaluate the steady-state pharmacokinetics (PK) of rilpivirine and determine the appropriate dose of rilpivirine in combination with other antiretrovirals (ARVs) in participants aged ≥2 to <12 years with a body weight of <25 kg.
• To evaluate the safety and tolerability of rilpivirine in combination with other ARVs in participants aged ≥2 to <12 years over a 24-week treatment period.

E.2.2

Secondary objectives of the trial

The secondary objectives are:
• To evaluate the safety and tolerability of rilpivirine in combination with other ARVs over a 48-week treatment period.
• To evaluate the efficacy of rilpivirine in combination with other ARVs over a 24- and 48-week treatment period.
• To evaluate population PK and PK/pharmacodynamic (PD) relationships for safety and efficacy of rilpivirine in combination with other ARVs.
• To assess resistance in case of loss of virologic response to rilpivirine in combination with other ARVs.
• To evaluate treatment adherence to rilpivirine in combination with other ARVs over a 24 and 48 week treatment period.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1. Aged ≥2 to <12 years at screening.
2. Weighing at least 11 kg at screening.
3. Have documented chronic HIV-1 infection.
4. On a stable ARV regimen for at least 6 months prior to screening and virologically suppressed, with documents evidence of at least 2 plasma viral loads <50 HIV-1 RNA copies/mL: one within 2-12 months prior to screening and one at screening.
5. Criterion deleted
6. Parent(s) (preferably both if available per local requirements) or the participant's legally acceptable representative[s]) must sign an ICF indicating that he or she understands the purpose of and procedures required for the study. Assent is also required from participants capable of understanding the nature of the study (typically aged ≥ 7 years)
7. Can comply with the protocol requirements.
8. Can switch from any ARV class.
9. Never been treated with a therapeutic HIV vaccine.
10. Otherwise healthy and medically stable on the basis of physical examination, medical history, vital signs, and 12-lead ECG performed at screening. If there are abnormalities, they must be consistent with the underlying illness in the study population. This determination must be recorded in the participant’s source documents and initialed by the investigator.

E.4

Principal exclusion criteria

Any potential participant who meets any of the following criteria will be excluded from participating in the study:
1. Have previously documented HIV-2 infection.
2. Have known or suspected acute (primary) HIV-1 infection.
3. Taken any disallowed concomitant therapies within 4 weeks before the planned first dose of study intervention.
4. A positive HLA-B*5701 test at screening (when the investigator considers ABC in the background regimen). In case of a positive test, ABC cannot be administered, but instead, the investigator can select another ARV in the background regimen.
HLA-B*5701 testing is not required for participants with prior documented negative results.
5. Any current or history of adrenal disorder.
6. Any active clinically significant diseases (eg, pancreatitis, cardiac dysfunction, active and significant psychiatric disorders, clinical suspicion of adrenal insufficiency, and hepatic impairment) or findings at screening or medical history that, in the investigator’s opinion, would compromise the outcome of the study.
7. A history of virologic failure to ARVs with or without availability of an HIV-1 genotype result at the time of failure.
8. Documented genotypic evidence of resistance to RPV or to the selected background ARVs from historical data available in the source documents.
9. A known clinically significant allergy, hypersensitivity, or intolerance to RPV or its excipients or to the selected background ARVs.
10. Criterion modified per Amendment 1
10.1 Received an investigational intervention (including investigational vaccines) containing an active substance or used an invasive investigational medical device within 90 days before the planned first dose of study intervention.

E.5 End points

E.5.1

Primary end point(s)

1. Area under the plasma concentration-time curve from time of administration up to 24 hours post dose of rilpivirine, as derived from the intensive PK assessments.
2. Incidence of grade 3/4 AEs, SAEs, HIV-related events (including acquired immune deficiency syndrome [AIDS]-defining illnesses and Stage-3-defining Opportunistic Illnesses in HIV Infection), and AEs leading to discontinuation of study intervention through 24 weeks of study treatment.

E.5.1.1

Timepoint(s) of evaluation of this end point

1. From time of administration up to 24 hours postdose of rilpivirine
2. Until 24 weeks

E.5.2

Secondary end point(s)

1. Incidence and severity of AEs/HIV-related events and their relatedness to RPV through 24 and 48 weeks of study treatment.
2. Change from baseline over time and shift in toxicity grades/abnormalities versus reference for clinical laboratory parameters, ECG parameters, vital signs, and physical examination through 24 and 48 weeks of study treatment.
3. Proportion of participants with HIV-1 RNA <50 and ≥50 copies/mL using the Food and Drug Administration (FDA) Snapshot approach through 24 and 48 weeks of study treatment.
4. Proportion of participants with HIV-1 RNA <400 and ≥400 copies/mL using the FDA Snapshot approach through 24 and 48 weeks of study treatment
5. Pharmacokinetic parameters of RPV (other than area under the plasma concentration-time curve [AUC]), as derived from the intensive PK assessments.
6. Pharmacokinetic parameters of rilpivirine, as derived by population PK modeling, through 24 and 48 weeks of study treatment.
7. Viral genotype at the time of virologic failure through 24 and 48 weeks of study treatment.
8. Treatment adherence, as assessed by the Pediatric European Network for the Treatment of AIDS (PENTA) adherence questionnaire and by study intervention accountability, through 24 and 48 weeks of study treatment.

E.5.2.1

Timepoint(s) of evaluation of this end point

1 to 4, 6 to 8: Through 24 and 48 weeks of study treatment

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability, resistance testing, treatment adherence, resistance-associated mutations (RAMs), RPV intake(only for participants scheduled for an intensive PK visit), treatment adherence, palatability and swallowability assessments

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

South Africa

Thailand

Uganda

Italy

Portugal

Romania

Spain

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Upon study completion, participants will be offered the opportunity to continue study treatment in the pediatric rollover study TMC278IFD3004. Participants who do not roll over in the pediatric study TMC278IFD3004 will be informed that study intervention will not be made available to them after they have completed/discontinued the study intervention phase and that they should return to their primary physician to determine standard of care.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-08-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-10-23

P. End of Trial
P.	End of Trial Status	Completed

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