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Clinical Trial Results:
AN OPEN-LABEL, MULTICENTER, MULTIPLE-DOSE PHARMACOKINETIC AND 48-WEEK SAFETY AND EFFICACY TRIAL OF MARAVIROC IN COMBINATION WITH OPTIMIZED BACKGROUND THERAPY FOR THE TREATMENT OF ANTIRETROVIRAL-EXPERIENCED CCR5-TROPIC HIV-1 INFECTED CHILDREN 2-18 YEARS OF AGE

Summary
EudraCT number	2008-006873-33
Trial protocol	ES PT IT GB FR Outside EU/EEA
Global end of trial date

Results information
Results version number	v2(current)
This version publication date	04 Oct 2019
First version publication date	14 Apr 2016
Other versions	v1
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

A4001031

ISRCTN number

US NCT number

NCT00791700

WHO universal trial number (UTN)

Sponsor organisation name

ViiV Healthcare

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom, TW8 9GS

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc, +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc, +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-000020-PIP01-07

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Interim

Date of interim/final analysis

11 Mar 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Main objective of the trial

This study aimed to: Primary objectives: • determine the PK profile(s) and dosing schedule(s) for MVC in treatment experienced HIV infected children and adolescents on different background therapies; • determine the safety and tolerability of MVC in HIV infected children and adolescents. Secondary objectives: • describe the efficacy of multiple dose administration of MVC in treatment experienced children infected with R5 HIV 1; • describe tropism changes over time

Protection of trial subjects

This study was designed and monitored in accordance with Pfizer standard operating procedures (SOPs), until transition to the Contract Research Organization (CRO) PAREXEL in November 2012, after which the study was monitored in accordance with CRO SOPs. Both Pfizer and CRO SOPs complied with the ethical principles of Good Clinical Practice (GCP) as required by the major regulatory authorities, and in accordance with the Declaration of Helsinki as amended by legal and regulatory requirements, as well as the general principles set forth in the International Ethical Guidelines for Biomedical Research Involving Human Subjects (Council for International Organizations of Medical Sciences 2002), Guidelines for GCP (International Conference on Harmonization 1996), and the Declaration of Helsinki (World Medical Association 2008). In addition, the study was conducted in accordance with the CSP, the International Conference on Harmonization guideline on GCP, and applicable local regulatory requirements and laws.

Background therapy

Optimized background treatment (OBT), consisting of 3 to 5 commercially available Anti-retroviral (ARV) agents were selected by the investigator and approved by Pfizer, on the basis of resistance testing, treatment history and safety considerations. Subjects with toxicity due to drugs in the OBT regimen were able to substitute a drug of the same class during the study in consultation with the medical monitor. All concomitant medications were recorded on the CRF. Although no other forms of therapy for the treatment of HIV infection will be allowed while on study medication, IVIG for the treatment of HIV infection is allowed. ARV agents comprising the OBT regimen were taken according to the manufacturer product labeling or local guidelines. Dose adjustments to Maraviroc (MVC) were made in subjects taking concomitant medications that significantly inhibit and/or induce CYP3A4. This is because MVC is a substrate for CYP3A4. Medications such as analgesics, antiinflammatory agents, antibiotics, and nutritional supplements other than those contraindicated (list below), could be used as needed. Contraindicated medications included but not limited to were immunomodulators (except interferon or IVIG), grapefruit or grapefruit related citrus fruits (eg, Seville oranges, pomelos) and St.John's Wort or other herbal therapies. The use of rifampin for the treatment mycobacterial infection for subjects in Stage 2 was allowed on a case-by-case basis with the approval of the study team. Rifampin was not allowed for subjects in Stage 1. Co-administration of isoniazid was allowed on an individual basis upon discussion with and approval of the study team.

Evidence for comparator

Actual start date of recruitment

22 Apr 2009

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

5 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Brazil: 6

Country: Number of subjects enrolled

Italy: 1

Country: Number of subjects enrolled

Portugal: 4

Country: Number of subjects enrolled

Puerto Rico: 1

Country: Number of subjects enrolled

South Africa: 62

Country: Number of subjects enrolled

Spain: 6

Country: Number of subjects enrolled

Thailand: 11

Country: Number of subjects enrolled

United States: 12

Worldwide total number of subjects

103

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This open-label, multicenter, multiple dose pharmacokinetic, safety and efficacy study enrolled 103 subjects at 24 sites in 8 countries. Data reported in this result summary is the 5 year safety update.

Screening details

Criteria such as the following were considered: HIV-1 infected treatment-experienced children and adolescents who were failing current ARV therapy or have failed their most recent ARV regimen, defined by plasma HIV-1 RNA>=1000 copies/mL, infected with only R5 HIV-1, and have ARV experience/intolerance of 6 months with at least 2 ARV drug classes.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Blinding implementation details

Open-label study

Are arms mutually exclusive

Yes

Cohort 1

Arm description

>=2 - <6 years of age, MVC liquid formulation

Arm type

Experimental

Investigational medicinal product name

Maraviroc

Investigational medicinal product code

UK-427,857

Other name

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

MVC liquid formulation (20 mg/ml)

Cohort 2

Arm description

>=6 - <12 years of age, MVC tablet formulation

Arm type

Experimental

Investigational medicinal product name

Maraviroc

Investigational medicinal product code

UK-427,857

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

MVC tablet formulation (25 mg, 75 mg, 150 mg)

Cohort 3

Arm description

>=6 - <12 years of age, MVC liquid formulation

Arm type

Experimental

Investigational medicinal product name

Maraviroc

Investigational medicinal product code

UK-427,857

Other name

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

MVC liquid formulation (20 mg/ml)

Cohort 4

Arm description

>=12 - <18 years of age, MVC tablet formulation

Arm type

Experimental

Investigational medicinal product name

Maraviroc

Investigational medicinal product code

UK-427,857

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

MVC tablet formulation (25 mg, 75 mg, 150 mg)

Number of subjects in period 1	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Started	16	31	13	43
Completed	10	20	7	13
Not completed	6	11	6	30
Adverse Event	-	-	1	1
Death	-	-	-	1
No longer willing to participate in study	1	1	-	8
Non-compliance with study treatment	-	2	-	4
Withdrawn due to pregnancy	-	-	-	1
Unspecified	-	1	-	1
Lost to follow-up	4	3	4	6
Insufficient clinical response	1	4	1	8

Baseline characteristics

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Reporting group title

Cohort 1

Reporting group description

>=2 - <6 years of age, MVC liquid formulation

Reporting group title

Cohort 2

Reporting group description

>=6 - <12 years of age, MVC tablet formulation

Reporting group title

Cohort 3

Reporting group description

>=6 - <12 years of age, MVC liquid formulation

Reporting group title

Cohort 4

Reporting group description

>=12 - <18 years of age, MVC tablet formulation

Reporting group values	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Total
Number of subjects	16	31	13	43	103
Age categorical
Units: Subjects
Children (2-11 years)	16	31	13	1	61
Adolescents (12-17 years)	0	0	0	42	42
Age Continuous \|
Units: years
arithmetic mean (standard deviation)	3.4 ± 0.9	9.1 ± 1.7	8.9 ± 2.0	14.0 ± 1.6	-
Gender, Male/Female
Units: participants
Female	5	16	6	27	54
Male	11	15	7	16	49

Subject analysis set title

Response

Subject analysis set type

Full analysis

Subject analysis set description

Subjects with plasma HIV-1 RNA <48 copies/mL at Week 48 using Missing, Switch, Discontinuation’=Failure (MSDF) algorithm.

Subject analysis set title

PDVF

Subject analysis set type

Full analysis

Subject analysis set description

Subjects with protocol-defined virologic failure

Subject analysis set title

Other Failure/Remainder

Subject analysis set type

Full analysis

Subject analysis set description

Subjects who discontinued due to other reasons.

Subject analysis set title

Cohort 1 (Grade 3)

Subject analysis set type

Safety analysis

Subject analysis set description

>=2 - <6 years of age, MVC liquid formulation

Subject analysis set title

Cohort 1 (Grade 4)

Subject analysis set type

Safety analysis

Subject analysis set description

>=2 - <6 years of age, MVC liquid formulation

Subject analysis set title

Cohort 2 (Grade 3)

Subject analysis set type

Safety analysis

Subject analysis set description

>=6 - <12 years of age, MVC tablet formulation

Subject analysis set title

Cohort 2 (Grade 4)

Subject analysis set type

Safety analysis

Subject analysis set description

>=6 - <12 years of age, MVC tablet formulation

Subject analysis set title

Cohort 3 (Grade 3)

Subject analysis set type

Safety analysis

Subject analysis set description

>=6 - <12 years of age, MVC liquid formulation

Subject analysis set title

Cohort 3 (Grade 4)

Subject analysis set type

Safety analysis

Subject analysis set description

>=6- <12years of age, MVC liquid formulation

Subject analysis set title

Cohort 4 (Grade 3)

Subject analysis set type

Safety analysis

Subject analysis set description

>=12 - <18 years of age, MVC tablet formulation

Subject analysis set title

Cohort 4 (Grade 4)

Subject analysis set type

Safety analysis

Subject analysis set description

>=12 - <18 years of age, MVC tablet formulation

Subject analysis sets values	Response	PDVF	Other Failure/Remainder	Cohort 1 (Grade 3)	Cohort 1 (Grade 4)	Cohort 2 (Grade 3)	Cohort 2 (Grade 4)	Cohort 3 (Grade 3)	Cohort 3 (Grade 4)	Cohort 4 (Grade 3)	Cohort 4 (Grade 4)
Number of subjects	49	23	31	16	16	31	31	13	13	43	43
Age categorical
Units: Subjects
Children (2-11 years)	0	0	0	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0	0	0
Age Continuous \|
Units: years
arithmetic mean (standard deviation)	0 ± 0	0 ± 0	0 ± 0	0 ± 0	0 ± 0	0 ± 0	0 ± 0	0 ± 0	0 ± 0	0 ± 0	0 ± 0
Gender, Male/Female
Units: participants
Female	0	0	0	0	0	0	0	0	0	0	0
Male	0	0	0	0	0	0	0	0	0	0	0

End points

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Reporting group title

Cohort 1

Reporting group description

>=2 - <6 years of age, MVC liquid formulation

Reporting group title

Cohort 2

Reporting group description

>=6 - <12 years of age, MVC tablet formulation

Reporting group title

Cohort 3

Reporting group description

>=6 - <12 years of age, MVC liquid formulation

Reporting group title

Cohort 4

Reporting group description

>=12 - <18 years of age, MVC tablet formulation

Subject analysis set title

Response

Subject analysis set type

Full analysis

Subject analysis set description

Subjects with plasma HIV-1 RNA <48 copies/mL at Week 48 using Missing, Switch, Discontinuation’=Failure (MSDF) algorithm.

Subject analysis set title

PDVF

Subject analysis set type

Full analysis

Subject analysis set description

Subjects with protocol-defined virologic failure

Subject analysis set title

Other Failure/Remainder

Subject analysis set type

Full analysis

Subject analysis set description

Subjects who discontinued due to other reasons.

Subject analysis set title

Cohort 1 (Grade 3)

Subject analysis set type

Safety analysis

Subject analysis set description

>=2 - <6 years of age, MVC liquid formulation

Subject analysis set title

Cohort 1 (Grade 4)

Subject analysis set type

Safety analysis

Subject analysis set description

>=2 - <6 years of age, MVC liquid formulation

Subject analysis set title

Cohort 2 (Grade 3)

Subject analysis set type

Safety analysis

Subject analysis set description

>=6 - <12 years of age, MVC tablet formulation

Subject analysis set title

Cohort 2 (Grade 4)

Subject analysis set type

Safety analysis

Subject analysis set description

>=6 - <12 years of age, MVC tablet formulation

Subject analysis set title

Cohort 3 (Grade 3)

Subject analysis set type

Safety analysis

Subject analysis set description

>=6 - <12 years of age, MVC liquid formulation

Subject analysis set title

Cohort 3 (Grade 4)

Subject analysis set type

Safety analysis

Subject analysis set description

>=6- <12years of age, MVC liquid formulation

Subject analysis set title

Cohort 4 (Grade 3)

Subject analysis set type

Safety analysis

Subject analysis set description

>=12 - <18 years of age, MVC tablet formulation

Subject analysis set title

Cohort 4 (Grade 4)

Subject analysis set type

Safety analysis

Subject analysis set description

>=12 - <18 years of age, MVC tablet formulation

Primary: Pharmacokinetic (PK) Parameters for subjects with data in Stage 1 enrolled in Stage 2 – Week 2 and Week 48

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End point title

Pharmacokinetic (PK) Parameters for subjects with data in Stage 1 enrolled in Stage 2 – Week 2 and Week 48 ^[1]

End point description

A PK analysis was performed using PK data from subjects that participated in Stage 1 (PK Populations 2 and 3) where intensive MVC PK data were available at Week 2. The primary aim of this analysis was to describe and summarize MVC PK parameters at Week 2 and Week 48 by cohort and OBT group. Geometric Coefficient of Variation is defined as the geometric standard deviation to the power of the reciprocal of the geometric mean. PK analysis was also performed for Population 2 (subset of APS 1) consisting of all Stage 1 subjects who had a Week 2 full PK profile; and for Population 3 (subset of APS 1) consisting of all Stage 1 subjects who had an approved dose for Stage 2 / met the PK target. Number of Subjects Analyzed signifies the number of subjects analyzed for PK. n= number of subjects analyzed at individual time points for this outcome measure.

End point type

Primary

End point timeframe

Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose)

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: No statistical analyses were done.

End point values	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Number of subjects analysed	16	31	12	42
Units: ng/mL
geometric mean (geometric coefficient of variation)
Cavg-Week2(n=12, 11, 10, 17)	237.34 ± 63	260.65 ± 43	264.45 ± 62	239.85 ± 67
Cavg-Week 48(n=9, 8, 8, 12)	163.73 ± 146	289.69 ± 50	168.62 ± 117	199.12 ± 78
Cmax-Week2 (n=12, 11, 10, 17)	581.47 ± 69	546.80 ± 51	444.37 ± 61	530.80 ± 62
Cmax-Week 48(n=9, 8, 8, 12)	334.68 ± 156	593.68 ± 25	284.96 ± 128	423.32 ± 48
Cmin-Week2(n=12, 11, 10, 17)	18.97 ± 202208	100.02 ± 39	115.84 ± 90	56.17 ± 145
Cmin-Week 48(n=9, 8, 8, 12)	48.11 ± 180	82.21 ± 120	60.03 ± 245	66.51 ± 140

No statistical analyses for this end point

Primary: PK Parameters for Stage 1 subjects Enrolled in Stage 2 – Week 2 and Week 48 Results for Stage 2 doses - AUCtau (Area under the curve at steady state)

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End point title

PK Parameters for Stage 1 subjects Enrolled in Stage 2 – Week 2 and Week 48 Results for Stage 2 doses - AUCtau (Area under the curve at steady state) ^[2]

End point description

A PK analysis was performed using PK data from participants that participated in Stage 1 (PK Populations 2 and 3) where intensive MVC PK data were available at Week 2. The primary aim of this analysis was to describe and summarize MVC PK parameters (AUCtau) at Week 2 and Week 48 by cohort and OBT group. Correlations between MVC PK and efficacy as well as compliance were also assessed. PK analysis was also performed for Population 2 (subset of APS 1) consisting of all Stage 1 participants who had a Week 2 full PK profile; and for Population 3 (subset of APS 1) consisting of all Stage 1 participants who had an approved dose for Stage 2 / met the PK target. Number of Subjects Analyzed signifies the number of subjects analyzed for PK. n= number of subjects analyzed at individual time points for this outcome measure.

End point type

Primary

End point timeframe

Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose)

Notes
[2] - 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: No statistical analyses were done.

End point values	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Number of subjects analysed	16	31	12	42
Units: ng*hr/mL
geometric mean (geometric coefficient of variation)
AUCtau - Week 2 (n=12, 11, 10, 17)	2848.1 ± 63	3127.7 ± 43	3173.4 ± 62	2878.2 ± 67
AUCtau - Week 48 (n=9, 8, 8, 12)	1964.7 ± 146	3476.3 ± 50	2023.5 ± 117	2389.4 ± 78

No statistical analyses for this end point

Primary: PK Parameters for Stage 1 subjects Enrolled in Stage 2 – Week 2 and Week 48 Results for Stage 2 doses - Tmax (Time at maximum concentration)

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End point title

PK Parameters for Stage 1 subjects Enrolled in Stage 2 – Week 2 and Week 48 Results for Stage 2 doses - Tmax (Time at maximum concentration) ^[3]

End point description

A PK analysis was performed using PK data from subjects that participated in Stage 1 (PK Populations 2 and 3) where intensive MVC PK data were available at Week 2. The primary aim of this analysis was to describe and summarize MVC PK parameters (Tmax) at Week 2 and Week 48 by cohort and OBT group. Correlations between MVC PK and efficacy as well as compliance were also assessed. PK analysis was also performed for Population 2 (subset of APS 1) consisting of all Stage 1 subjects who had a Week 2 full PK profile; and for Population 3 (subset of APS 1) consisting of all Stage 1 subjects who had an approved dose for Stage 2 / met the PK target. Number of Subjects Analyzed signifies the number of subjects analyzed for PK. n= number of subjects analyzed at individual time points for this outcome measure.

End point type

Primary

End point timeframe

Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose)

Notes
[3] - 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: No statistical analyses were done.

End point values	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Number of subjects analysed	16	31	12	42
Units: hour
median (full range (min-max))
Tmax - Week 2 (n=12, 11, 10, 17)	2.000 (0.97 to 6.00)	4.000 (0.75 to 6.00)	2.000 (1.00 to 4.00)	2.000 (1.00 to 4.00)
Tmax - Week 48 (n=9, 8, 8, 12)	2.000 (0.00 to 6.03)	2.000 (1.00 to 8.00)	3.000 (0.00 to 6.00)	2.000 (1.00 to 4.00)

No statistical analyses for this end point

Primary: Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events (All Causality)

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End point title

Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events (All Causality) ^[4]

End point description

Safety analysis was performed on all subjects who received at least 1 dose of study drug. It was assessed by spontaneous reports, physical examination and laboratory test results in all subjects who received at least 1 dose of study drug. The investigator used the Division of AIDS (DAIDS) version 4 Table for Grading the Severity of Adult and Pediatric AEs. MCT disorders= Musculoskeletal and Connective Tissue Disorder.

End point type

Primary

End point timeframe

Baseline up to 5 years

Notes
[4] - 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: No statistical analyses were done.

End point values	Cohort 1 (Grade 3)	Cohort 1 (Grade 4)	Cohort 2 (Grade 3)	Cohort 2 (Grade 4)	Cohort 3 (Grade 3)	Cohort 3 (Grade 4)	Cohort 4 (Grade 3)	Cohort 4 (Grade 4)
Number of subjects analysed	16	16	31	31	13	13	43	43
Units: Number of events
Gastrointestinal disorders - Vomiting	1	0	1	0	0	0	0	0
Hepat. disorders - Drug-induced liver injury	0	0	0	0	0	0	0	1
Infections and infestations - H1N1 influenza	0	0	0	0	0	0	1	0
Infections and infestations - Pneumonia	0	0	0	0	1	0	1	0
Investigations - Lipase increased	0	1	0	0	0	0	0	0
Pyschiatric disorder - Bipolar disorder	0	0	1	0	0	0	0	0
Gastrointestinal disorders - Gastritis	0	0	1	0	0	0	0	0
Investigations - Hepatic enzyme abnormal	0	0	1	0	0	0	0	0
Investigations - Transaminases increased	0	0	1	0	0	0	0	0
Pyschiatric disorder - Aggression	0	0	1	0	0	0	0	0
Blood and lymphatic system disorders - Anaemia	0	0	0	0	0	0	1	0
Infections and infestations - Meningitis	0	0	0	0	0	0	0	1
Otitis media	0	0	1	0	0	0	0	0

No statistical analyses for this end point

Primary: Treatment discontinuation secondary to Serious Adverse Event (SAE) related to study drug

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End point title

Treatment discontinuation secondary to Serious Adverse Event (SAE) related to study drug ^[5]

End point description

The primary reason for a subject discontinuing from study drug or the clinical study was recorded in the source documents as well as the case report form. A discontinuation had to be reported immediately to the study medical monitor or his/her designated representative if it was due to an SAE. Safety analysis was performed on all subjects who received at least 1 dose of study drug. In this study, there was no treatment discontinuation secondary to Serious Adverse Event (SAE) related to study drug.

End point type

Primary

End point timeframe

Baseline up to 5 years

Notes
[5] - 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: No statistical analyses were done.

End point values	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Number of subjects analysed	16	31	13	43
Units: subejcts	0	0	0	0

No statistical analyses for this end point

Secondary: Percentage of subjects with HIV‑1 RNA <400 copies/mL through Week 48 (MSDF)

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End point title

Percentage of subjects with HIV‑1 RNA <400 copies/mL through Week 48 (MSDF)

End point description

The proportion of subjects who achieved HIV-1 RNA <400 copies/mL at week 24 or 48 was assessed according to Food and Drug Administration’s (FDA’s) MSDF Snapshot algorithm. The algorithm uses the plasma HIV-1 RNA in the Week 24 or 48 visit window, follows the “virology-first principle” and considers a subject who has a missing plasma HIV-1 RNA, or switches to prohibited ARV regimen or discontinues from the study or study drug for any reason, or dies, as a failure. The percentage of subjects is reported below.

End point type

Secondary

End point timeframe

Week 24 and Week 48 post-treatment

End point values	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Number of subjects analysed	16	31	13	43
Units: percentage of subjects
number (not applicable)
Week 24	68.8	90.3	69.2	62.8
Week 48	75.0	77.4	69.2	51.2

No statistical analyses for this end point

Secondary: Percentage of subjects with HIV‑1 RNA <48 copies/mL through Week 48 (MSDF)

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End point title

Percentage of subjects with HIV‑1 RNA <48 copies/mL through Week 48 (MSDF)

End point description

The proportion of subjects who achieved HIV-1 RNA <48 copies/mL at week 24 or 48 was assessed according to Food and Drug Administration’s (FDA’s) MSDF Snapshot algorithm. The algorithm uses the plasma HIV-1 RNA in the Week 24 or 48 visit window, follows the “virology-first principle” and considers a subject who has a missing plasma HIV-1 RNA, or switches to prohibited ARV regimen or discontinues from the study or study drug for any reason, or dies, as a failure. The percentage of subjects is reported below. The FAS consisted of all subjects who received at least 1 dose of study drug.

End point type

Secondary

End point timeframe

Week 24 and Week 48 post-treatment

End point values	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Number of subjects analysed	16	31	13	43
Units: percentage of subjects
number (not applicable)
Week 24	25.0	64.5	61.5	48.8
Week 48	50.0	54.8	53.8	39.5

No statistical analyses for this end point

Secondary: Percentage of Subjects with HIV-1 RNA Levels <400 copies/mL at Weeks 24 and 48 using Missing, Discontinuation = Failure (MD=F) Approach

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End point title

Percentage of Subjects with HIV-1 RNA Levels <400 copies/mL at Weeks 24 and 48 using Missing, Discontinuation = Failure (MD=F) Approach

End point description

Subjects who have been discontinued from the study, have been lost to follow-up, or have missing HIV-1 RNA data prior to the time point of interest were considered to have HIV-1 RNA levels > lower limit of quantification (LLOQ) . This will be referred to as [non-completer = failure; NC=F] or [missing, discontinuation = failure; MD=F]. The proportion of subjects (100*n/N) is reported below. The FAS consisted of all subjects who received at least 1 dose of study drug.

End point type

Secondary

End point timeframe

Week 24 and Week 48 post-treatment

End point values	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Number of subjects analysed	16	31	13	43
Units: percentage of subjects
number (confidence interval 95%)
Week 24 (n=10, 27, 8, 27)	62.5 (38.8 to 86.2)	87.10 (75.3 to 98.9)	69.2 (44.1 to 94.3)	62.8 (48.3 to 77.2)
Week 48 (n=12, 23, 9, 22)	75.0 (53.8 to 96.2)	74.2 (58.8 to 89.6)	69.2 (44.1 to 94.3)	51.2 (36.2 to 66.1)

No statistical analyses for this end point

Secondary: Percentage of Subjects with HIV-1 RNA Levels < 48 copies/mL at Weeks 24 and 48 using MD=F Approach

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End point title

Percentage of Subjects with HIV-1 RNA Levels < 48 copies/mL at Weeks 24 and 48 using MD=F Approach

End point description

End point type

Secondary

End point timeframe

Week 24 and Week 48 post-treatment

End point values	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Number of subjects analysed	16	31	13	43
Units: Percentage of Subjects
number (confidence interval 95%)
Week 24 (n=3, 20, 8, 21)	18.8 (0.0 to 37.9)	64.5 (47.7 to 81.4)	61.5 (35.1 to 89.0)	48.8 (33.9 to 63.8)
Week 48 (n=8, 16, 8, 17)	50.0 (25.5 to 74.5)	51.6 (34.0 to 69.2)	61.5 (35.1 to 89.0)	39.5 (24.9 to 54.2)

No statistical analyses for this end point

Secondary: Percentage of subjects with HIV-1 RNA < 400 copies/mL and <48 copies/mL using the time to loss of virologic response algorithm (TLOVR) at Week 48

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End point title

Percentage of subjects with HIV-1 RNA < 400 copies/mL and <48 copies/mL using the time to loss of virologic response algorithm (TLOVR) at Week 48

End point description

TLOVR is defined as the time from first dose of study medication (Day 1) until the time of virologic failure using the a TLOVR algorithm. The FAS consisted of all subjects who received at least 1 dose of study drug.

End point type

Secondary

End point timeframe

Week 48

End point values	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Number of subjects analysed	16	31	13	43
Units: Percentage of subjects
number (not applicable)
<400 copies/mL; TLOVR Responder	62.5	74.2	69.2	48.8
<48 copies/mL; TLOVR Responder	43.8	54.8	46.2	44.2

No statistical analyses for this end point

Secondary: Percentage of Subjects with >= 1.0 log10 reduction in HIV-1RNA concentration from baseline to Week 24 and Week 48

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End point title

Percentage of Subjects with >= 1.0 log10 reduction in HIV-1RNA concentration from baseline to Week 24 and Week 48

End point description

Percentage of subjects with at least a 1.0 log10 reduction in HIV-1 RNA from baseline to Week 24 and Week 48 were tabulated and is presented below. The number of subjects with an observation at specified time points were used to calculate the percentage.

End point type

Secondary

End point timeframe

Week 24 and Week 48 post-treatment

End point values	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Number of subjects analysed	16	31	13	43
Units: percentage of subjects
number (confidence interval 95%)
Week 24	92.3 (77.8 to 106.8)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	93.1 (83.9 to 102.3)
Week 48	100.0 (100.0 to 100.0)	96.2 (88.8 to 103.6)	100.0 (100.0 to 100.0)	88.0 (75.3 to 100.7)

No statistical analyses for this end point

Secondary: Summary of Change from Baseline in HIV-1 RNA (Original) at Week 24 and Week 48

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End point title

Summary of Change from Baseline in HIV-1 RNA (Original) at Week 24 and Week 48

End point description

Plasma HIV-1 RNA was determined using the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 Test (lower limit of quantification [LLOQ] <48 copies/mL). Blood samples were taken at the time points indicated in the subject evaluation schedule. Screening HIV-1 RNA >1000 copies/ml was used to determine eligibility for the study. The FAS consisted of all subjects who received at least 1 dose of study drug. LOCF was used to impute missing values.

End point type

Secondary

End point timeframe

Week 24 and Week 48 post-treatment

End point values	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Number of subjects analysed	15	31	12	39
Units: copies/mL
arithmetic mean (standard deviation)
Change from Baseline - Original - Week 24	-271974.6 ± 391843.59	-38764.0 ± 63688.93	-58081.0 ± 79720.33	-57325.7 ± 172108.62
Change from Baseline - Original - Week 48	-267834.2 ± 378896.88	-34787.7 ± 60222.60	-56351.7 ± 76231.03	-55321.1 ± 173840.55

No statistical analyses for this end point

Secondary: Change from Baseline in cluster of differentiation 4 (CD4+) cell count at weeks 24 and 48

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End point title

Change from Baseline in cluster of differentiation 4 (CD4+) cell count at weeks 24 and 48

End point description

Change from baseline in CD4 cell count to Week 24 and Week 48 were tabulated in aggregated and broken down by age cohort using summary statistics. The FAS consisted of all subjects who received at least 1 dose of study drug. LOCF was used to impute missing values.

End point type

Secondary

End point timeframe

Week 24 and Week 48 post-treatment

End point values	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Number of subjects analysed	15	30	12	39
Units: cells/mm^3
arithmetic mean (standard deviation)
Week 24	232.7 ± 381.6	355.8 ± 294.0	213.9 ± 166.4	173.6 ± 203.6
Week 48	275.9 ± 363.4	362.7 ± 373.5	167.3 ± 150.9	168.6 ± 211.0

No statistical analyses for this end point

Secondary: Change from Baseline in CD4+ % at weeks 24 and 48

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End point title

Change from Baseline in CD4+ % at weeks 24 and 48

End point description

Change from baseline in CD4 % to Week 24 and Week 48 were tabulated in aggregated and broken down by age cohort using summary statistics. The FAS consisted of all subjects who received at least 1 dose of study drug. LOCF was used to impute missing values.

End point type

Secondary

End point timeframe

Week 24 and Week 48 post-treatment

End point values	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Number of subjects analysed	15	31	12	39
Units: percentage of CD4+ cells
arithmetic mean (standard deviation)
Week 24 (n=15, 31, 12, 39)	7.3 ± 5.0	3.8 ± 7.4	3.5 ± 4.0	3.8 ± 6.1
Week 48 (n=15, 31, 12, 39)	7.5 ± 7.6	6.0 ± 6.8	2.5 ± 4.2	4.6 ± 6.5

No statistical analyses for this end point

Secondary: Protocol Defined Virologic Failure

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End point title

Protocol Defined Virologic Failure

End point description

The occurrence of any one of the following criteria would constitute Virologic failure: A=Decrease from Baseline plasma HIV-1 RNA <1 log10 and plasma HIV-1 RNA >400 copies/mL starting at Week 12 and confirmed at consecutive Week 16; B=Decrease from Baseline plasma HIV-1 RNA <2.0 log10 and plasma HIV-1 RNA >400 copies/mL at Week 24 OR plasma HIV-1 RNA >10,000 copies/mL on and after Week 24, and confirmed within 14 to 21 days; C=Increase from nadir plasma HIV-1 RNA of >=1 log10 (>=1,000 copies/mL if nadir plasma HIV-1 RNA <48 copies/mL) at any time, and confirmed within 14 to 21 days. The FAS consisted of all subjects who received at least 1 dose of study drug.

End point type

Secondary

End point timeframe

Week 48

End point values	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Number of subjects analysed	16	31	13	43
Units: Number of subjects
A (measure description above)	0	2	1	5
B (measure description above)	0	0	0	0
C (measure description above)	3	3	2	8
Number of PDVF	3	5	3	13

No statistical analyses for this end point

Secondary: Shift Table of Viral Tropism between Screening and Confirmed PDVF Prior to Week 48

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End point title

Shift Table of Viral Tropism between Screening and Confirmed PDVF Prior to Week 48

End point description

Virus tropism was determined using the Monogram Biosciences Trofile™ viral tropism assay. A shift table of the change in detected tropism from screening to the time of failure was produced in the aggregate and also broken down by age cohort. Subjects who experienced confirmed PDVF through Week 48 with sufficient plasma HIV-1 RNA for virology analysis while receiving MVC. One subject was excluded from summary tables as classified as MSDF response; one subject was analyzed after stopping treatment.

End point type

Secondary

End point timeframe

Screening and Week 48

End point values	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Number of subjects analysed	3	4	3	13
Units: Number of subjects
With valid on-treatment results	2	4	3	11
Tropism at Confirmed PDVF R5	2	3	2	9
Tropism at Confirmed PDVF DM	0	1	1	2
Tropism at Confirmed PDVF X4	0	0	0	0
Tropism at Confirmed PDVF Not Reportable	1	0	0	1

No statistical analyses for this end point

Secondary: Summary of the Emergence of reverse transcriptase inhibitor (RTI) and protease inhibitor (PI) resistance associated mutations (RAMs) Between Screening and On-Treatment Confirmed PDVF: Total and by Cohort Prior to Week 48

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End point title

Summary of the Emergence of reverse transcriptase inhibitor (RTI) and protease inhibitor (PI) resistance associated mutations (RAMs) Between Screening and On-Treatment Confirmed PDVF: Total and by Cohort Prior to Week 48

End point description

Phenotypic and genotypic susceptibility to reverse transcriptase and protease inhibitors was evaluated at screening using the Monogram Biosciences PhenoSense™ GT (PSGT) assay. Samples from a confirmatory PDVF visit or early termination of MVC were planned to be analyzed if the plasma HIV-1 RNA was ≥400 copies/mL. Subjects with more than one mutation are counted more than once. One subject was excluded from summary tables as classified as MSDF response; one participant was analyzed after stopping treatment.

End point type

Secondary

End point timeframe

48 weeks

End point values	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Number of subjects analysed	3	4	3	13
Units: Number of subjects
With valid on-treatment results	2	4	3	11
PI Minor (L10L/F, L89L/I/M, V77V/I and K20K/R)	0	0	2	3
PI Major	0	0	0	0
NNRTI (K103K/N and K103N)	0	1	1	1
NRTI M184V	0	0	1	0
Total with emergence	0	1	3	4

No statistical analyses for this end point

Secondary: Optimized Background Treatment (OBT) Susceptibility Scores (Net/Overall) by Outcome

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End point title

Optimized Background Treatment (OBT) Susceptibility Scores (Net/Overall) by Outcome

End point description

Outcome (Response, PDVF or other/remainder) was summarized by the total ARV activity of the background regimen using simple and weighted totals (TOBT and p-wTOBTss, respectively) in the aggregate, categorized as 0, 1, ≥2 (TOBT) and 0 0.5, 1 1.5 and ≥2 (p-wOBTss) respectively, as well as by screening genotype. Six subjects (Response: n=5; Other failure: n=1) failed to have successful PhenoSense GT analysis at screening, and so a net susceptibility score was not generated. One more subject was not included in the wOBTss analysis due to failed phenotype analysis. However, net susceptibility scores were imputed for simple analysis based on genotype. The FAS consisted of all subjects who received at least 1 dose of study drug. Susceptibility scores indicate the level resistance to the study medication. Scores include: 1 = susceptible and potential low-level resistance; 0.5 = low and intermediate-level resistance; 0 = high-level resistance.

End point type

Secondary

End point timeframe

48 weeks

End point values	Response	PDVF	Other Failure/Remainder
Number of subjects analysed	49	23	31
Units: Percentage of subjects
number (not applicable)
Simple score 0	0	0	0
Simple score 1.0	8.2	4.3	0
Simple score ≥ 2.0	81.6	95.7	96.8
Weighted score 0-0.5	6.1	30.4	29.0
Weighted score 1.0-1.5	53.1	65.2	29.0
Weighted score ≥ 2.0	28.6	4.3	38.7

No statistical analyses for this end point

Secondary: Summary of Change from Baseline in HIV-1 RNA (Log10 copies/mL) at Week 24 and Week 48

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End point title

Summary of Change from Baseline in HIV-1 RNA (Log10 copies/mL) at Week 24 and Week 48

End point description

Plasma HIV-1 RNA was determined using the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 Test (lower limit of quantification [LLOQ] <48 copies/mL). Blood samples were taken at the time points indicated in the participant evaluation schedule. Screening HIV-1 RNA >1000 copies/ml was used to determine eligibility for the study.

End point type

Secondary

End point timeframe

Week 24 and Week 48 post-treatment

End point values	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Number of subjects analysed	15	31	12	39
Units: Log10 Copies/mL
arithmetic mean (standard deviation)
Change from Baseline - Log10 - Week 24	-2.4853 ± 1.1421	-2.2324 ± 0.8668	-2.1756 ± 1.1854	-1.6482 ± 1.3806
Change from Baseline - Log10 - Week 48	-2.5831 ± 1.2148	-1.9579 ± 1.0861	-2.0549 ± 1.2125	-1.4591 ± 1.4477

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline up to 5 years

Adverse event reporting additional description

The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as non-serious in another subject, or 1 subject may have experienced both a serious and non-serious event during the study.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

21.1

Reporting group title

Cohort 1

Reporting group description

>=2 - <6 years of age, MVC liquid formulation

Reporting group title

Cohort 2

Reporting group description

>=6 - <12 years of age, MVC tablet formulation

Reporting group title

Cohort 3

Reporting group description

>=6 - <12 years of age, MVC liquid formulation

Reporting group title

Cohort 4

Reporting group description

>=12 - <18 years of age, MVC tablet formulation

Serious adverse events	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Total subjects affected by serious adverse events
subjects affected / exposed	5 / 16 (31.25%)	5 / 31 (16.13%)	3 / 13 (23.08%)	10 / 43 (23.26%)
number of deaths (all causes)	0	0	0	1
number of deaths resulting from adverse events	0	0	0	0
Investigations
Transaminases increased
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Otorrhoea
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Gastric fistula
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Drug-induced liver injury
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Hyperventilation
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Prurigo
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Bipolar disorder
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Osteopenia
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pain in extremity
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tendon disorder
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Abscess oral
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
H1N1 influenza
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pelvic inflammatory disease
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	1 / 13 (7.69%)	2 / 43 (4.65%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary tuberculosis
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tooth abscess
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Meningitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Total subjects affected by non serious adverse events
subjects affected / exposed	12 / 16 (75.00%)	25 / 31 (80.65%)	10 / 13 (76.92%)	34 / 43 (79.07%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	2 / 43 (4.65%)
occurrences all number	0	0	0	2
Vascular disorders
Hypertension
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Surgical and medical procedures
Tooth extraction
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	0	0	0
Pregnancy, puerperium and perinatal conditions
Pregnancy
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Fatigue
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	1	0	1
Influenza like illness
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Malaise
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	2	0	1
Pyrexia
subjects affected / exposed	2 / 16 (12.50%)	1 / 31 (3.23%)	2 / 13 (15.38%)	5 / 43 (11.63%)
occurrences all number	3	1	2	7
Immune system disorders
Allergy to arthropod bite
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Reproductive system and breast disorders
Amenorrhoea
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	2	0	0
Breast enlargement
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Breast mass
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Breast pain
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Dysmenorrhoea
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	1	0	1
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	2	0	0
Bronchospasm
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	3	0	0	0
Catarrh
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	0	0	0
Cough
subjects affected / exposed	1 / 16 (6.25%)	6 / 31 (19.35%)	2 / 13 (15.38%)	3 / 43 (6.98%)
occurrences all number	2	15	3	4
Epistaxis
subjects affected / exposed	1 / 16 (6.25%)	2 / 31 (6.45%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	2	0	0
Nasal congestion
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	1 / 13 (7.69%)	1 / 43 (2.33%)
occurrences all number	0	1	1	1
Hyperventilation
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Oropharyngeal pain
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	2	0	1
Pharyngeal disorder
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Productive cough
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	1 / 43 (2.33%)
occurrences all number	0	0	1	1
Respiratory disorder
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Rhinitis allergic
subjects affected / exposed	0 / 16 (0.00%)	2 / 31 (6.45%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	2	0	1
Rhinorrhoea
subjects affected / exposed	0 / 16 (0.00%)	2 / 31 (6.45%)	1 / 13 (7.69%)	2 / 43 (4.65%)
occurrences all number	0	5	2	2
Rhonchi
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Bronchial hyperreactivity
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	0	0	0
Allergic cough
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Psychiatric disorders
Attention deficit/hyperactivity disorder
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 43 (0.00%)
occurrences all number	0	0	2	0
Hallucination
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Depression
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	2 / 43 (4.65%)
occurrences all number	0	0	0	2
Insomnia
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Nightmare
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0
Panic disorder
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Aggression
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Flat affect
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Investigations
Blood HIV RNA increased
Additional description: From informed consent to 30 days after last MVC dose and within a frequency threshold of 2%.
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	0	0	0
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0
Blood iron decreased
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Blood phosphorus decreased
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0
Cardiac murmur
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0
Hepatic enzyme abnormal
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	2	0	0
Hepatic enzyme increased
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 43 (0.00%)
occurrences all number	1	0	2	0
Lipase increased
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	0	0	0
Neutrophil count decreased
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	2 / 43 (4.65%)
occurrences all number	0	0	0	3
Viral load increased
Additional description: From informed consent to 30 days after last MVC dose and within a frequency threshold of 2%.
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Weight decreased
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0
Weight increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	2 / 43 (4.65%)
occurrences all number	0	0	0	2
Haemoglobin decreased
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Injury, poisoning and procedural complications
Accidental exposure to product
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Arthropod bite
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Arthropod sting
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Contusion
subjects affected / exposed	0 / 16 (0.00%)	2 / 31 (6.45%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	2	0	0
Fall
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Foot fracture
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Head injury
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Ligament sprain
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Injury
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0
Limb injury
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	1	0	1
Muscle strain
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	2
Overdose
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	2	0	1
Skin abrasion
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	2 / 43 (4.65%)
occurrences all number	0	1	0	3
Thermal burn
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	0	0	0
Underdose
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Accidental overdose
subjects affected / exposed	1 / 16 (6.25%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	1	0	0
Ankle fracture
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	0	0	0
Traumatic ulcer
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Traumatic haematoma
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Cardiac disorders
Cardiac disorder
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	3 / 43 (6.98%)
occurrences all number	0	1	0	4
Epilepsy
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Generalised tonic-clonic seizure
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	3	0	0
Headache
subjects affected / exposed	0 / 16 (0.00%)	2 / 31 (6.45%)	2 / 13 (15.38%)	6 / 43 (13.95%)
occurrences all number	0	4	3	10
Lethargy
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0
Somnolence
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Tension headache
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	2 / 43 (4.65%)
occurrences all number	0	0	0	11
Intellectual disability
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	3 / 43 (6.98%)
occurrences all number	1	0	0	4
Iron deficiency anaemia
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	0	0	0
Lymphadenitis
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 43 (0.00%)
occurrences all number	1	0	1	0
Lymphadenopathy
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	5 / 43 (11.63%)
occurrences all number	1	0	0	5
Neutropenia
subjects affected / exposed	2 / 16 (12.50%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	3	0	0	0
Ear and labyrinth disorders
Deafness
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Cerumen impaction
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Ear haemorrhage
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Eye disorders
Conjunctival pallor
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	2	0	0
Conjunctivitis allergic
subjects affected / exposed	1 / 16 (6.25%)	2 / 31 (6.45%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	1	2	0	1
Hypermetropia
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Refraction disorder
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Abdominal pain
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	2 / 13 (15.38%)	4 / 43 (9.30%)
occurrences all number	0	1	3	5
Abdominal pain lower
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0
Abdominal pain upper
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Anal pruritus
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Constipation
subjects affected / exposed	2 / 16 (12.50%)	1 / 31 (3.23%)	0 / 13 (0.00%)	2 / 43 (4.65%)
occurrences all number	2	1	0	3
Dental caries
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	1 / 13 (7.69%)	1 / 43 (2.33%)
occurrences all number	0	1	1	1
Diarrhoea
subjects affected / exposed	7 / 16 (43.75%)	3 / 31 (9.68%)	4 / 13 (30.77%)	9 / 43 (20.93%)
occurrences all number	12	3	4	10
Dyspepsia
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	2
Flatulence
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Gingival swelling
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Mouth ulceration
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	1 / 13 (7.69%)	1 / 43 (2.33%)
occurrences all number	1	0	1	1
Nausea
subjects affected / exposed	0 / 16 (0.00%)	3 / 31 (9.68%)	0 / 13 (0.00%)	5 / 43 (11.63%)
occurrences all number	0	3	0	5
Odynophagia
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Proctitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Salivary gland mucocoele
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Tongue disorder
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Toothache
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Vomiting
subjects affected / exposed	6 / 16 (37.50%)	8 / 31 (25.81%)	3 / 13 (23.08%)	4 / 43 (9.30%)
occurrences all number	15	9	4	5
Hepatobiliary disorders
Hepatotoxicity
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Hyperbilirubinaemia
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	2 / 43 (4.65%)
occurrences all number	0	0	0	2
Skin and subcutaneous tissue disorders
Acanthosis nigricans
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Acne
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	2 / 43 (4.65%)
occurrences all number	0	0	0	2
Dermatitis
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	2 / 43 (4.65%)
occurrences all number	2	0	0	2
Dermatitis allergic
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Dermatitis contact
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Dermatitis diaper
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	0	0	0
Dry skin
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	2 / 13 (15.38%)	1 / 43 (2.33%)
occurrences all number	0	0	2	1
Ecchymosis
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	0	0	0
Eczema
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	1 / 43 (2.33%)
occurrences all number	0	0	1	1
Papule
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Prurigo
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Rash pruritic
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	1	0	1
Rash
subjects affected / exposed	3 / 16 (18.75%)	1 / 31 (3.23%)	1 / 13 (7.69%)	1 / 43 (2.33%)
occurrences all number	4	3	1	1
Skin lesion
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	2 / 13 (15.38%)	0 / 43 (0.00%)
occurrences all number	0	0	2	0
Urticaria
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Urticaria papular
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	2	0	0
Lipodystrophy acquired
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Neurodermatitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 16 (0.00%)	2 / 31 (6.45%)	0 / 13 (0.00%)	2 / 43 (4.65%)
occurrences all number	0	2	0	2
Back pain
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Bone swelling
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Bursitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Joint swelling
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Musculoskeletal discomfort
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Myofascial pain syndrome
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Osteoporosis
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0
Pain in extremity
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	1 / 13 (7.69%)	1 / 43 (2.33%)
occurrences all number	0	1	1	1
Musculoskeletal stiffness
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Myalgia
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	0	0	0
Infections and infestations
Abscess
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	2 / 43 (4.65%)
occurrences all number	0	0	0	2
Acarodermatitis
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Angular cheilitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Bacterial vaginosis
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Bronchitis
subjects affected / exposed	3 / 16 (18.75%)	3 / 31 (9.68%)	0 / 13 (0.00%)	7 / 43 (16.28%)
occurrences all number	9	12	0	9
Bullous impetigo
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Conjunctivitis
subjects affected / exposed	2 / 16 (12.50%)	2 / 31 (6.45%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	3	2	0	1
Cystitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Ear infection
subjects affected / exposed	1 / 16 (6.25%)	1 / 31 (3.23%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	1	1	0	1
Fungal skin infection
subjects affected / exposed	1 / 16 (6.25%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	1	0	0
Gastroenteritis
subjects affected / exposed	3 / 16 (18.75%)	0 / 31 (0.00%)	2 / 13 (15.38%)	2 / 43 (4.65%)
occurrences all number	3	0	2	4
Gastroenteritis viral
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	0	0	0
Gingivitis
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	1	0	0	1
Herpes virus infection
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	0	0	0
Hordeolum
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Impetigo
subjects affected / exposed	1 / 16 (6.25%)	1 / 31 (3.23%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	1	3	0	1
Influenza
subjects affected / exposed	2 / 16 (12.50%)	6 / 31 (19.35%)	3 / 13 (23.08%)	5 / 43 (11.63%)
occurrences all number	4	9	5	5
Latent tuberculosis
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Lice infestation
subjects affected / exposed	0 / 16 (0.00%)	2 / 31 (6.45%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	3	0	1
Nasopharyngitis
subjects affected / exposed	4 / 16 (25.00%)	4 / 31 (12.90%)	0 / 13 (0.00%)	3 / 43 (6.98%)
occurrences all number	7	6	0	4
Oral herpes
subjects affected / exposed	1 / 16 (6.25%)	2 / 31 (6.45%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	1	3	0	1
Otitis externa
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	2 / 43 (4.65%)
occurrences all number	1	0	0	2
Otitis media
subjects affected / exposed	6 / 16 (37.50%)	1 / 31 (3.23%)	1 / 13 (7.69%)	0 / 43 (0.00%)
occurrences all number	9	1	1	0
Otitis media acute
subjects affected / exposed	2 / 16 (12.50%)	2 / 31 (6.45%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	9	2	0	0
Otitis media chronic
subjects affected / exposed	2 / 16 (12.50%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	2	0	0	0
Paronychia
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0
Parotitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Pharyngitis
subjects affected / exposed	1 / 16 (6.25%)	1 / 31 (3.23%)	0 / 13 (0.00%)	2 / 43 (4.65%)
occurrences all number	1	1	0	2
Oropharyngeal candidiasis
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Pharyngotonsillitis
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	2	0	0	0
Pneumonia
subjects affected / exposed	0 / 16 (0.00%)	3 / 31 (9.68%)	0 / 13 (0.00%)	2 / 43 (4.65%)
occurrences all number	0	3	0	2
Pneumonia bacterial
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Rhinitis
subjects affected / exposed	3 / 16 (18.75%)	1 / 31 (3.23%)	0 / 13 (0.00%)	3 / 43 (6.98%)
occurrences all number	5	1	0	5
Sinobronchitis
subjects affected / exposed	0 / 16 (0.00%)	2 / 31 (6.45%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	2	0	0
Sinusitis
subjects affected / exposed	1 / 16 (6.25%)	1 / 31 (3.23%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	1	1	0	1
Tinea capitis
subjects affected / exposed	2 / 16 (12.50%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	2	1	0	0
Tinea faciei
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Tinea infection
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	0	0	0
Tonsillitis
subjects affected / exposed	1 / 16 (6.25%)	2 / 31 (6.45%)	0 / 13 (0.00%)	2 / 43 (4.65%)
occurrences all number	1	2	0	2
Tooth abscess
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	1 / 13 (7.69%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0
Tracheitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Upper respiratory tract infection
subjects affected / exposed	7 / 16 (43.75%)	6 / 31 (19.35%)	2 / 13 (15.38%)	5 / 43 (11.63%)
occurrences all number	23	9	2	5
Tuberculosis
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Varicella
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	0	0	0
Viral infection
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	3
Viral upper respiratory tract infection
subjects affected / exposed	3 / 16 (18.75%)	2 / 31 (6.45%)	3 / 13 (23.08%)	1 / 43 (2.33%)
occurrences all number	4	2	4	2
Vulvovaginitis
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Wound infection
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	2 / 43 (4.65%)
occurrences all number	0	0	0	2
Conjunctivitis bacterial
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	0	0	0
Mastoiditis
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Viral rash
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	1	0	0	0
Fungal infection
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Pulmonary tuberculosis
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Urinary tract infection
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	1	0	1
Dehydration
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Hyperglycaemia
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	0	0
Hypertriglyceridaemia
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	2	0	1
Hypokalaemia
subjects affected / exposed	1 / 16 (6.25%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	1	0	0	1
Insulin resistance
subjects affected / exposed	0 / 16 (0.00%)	1 / 31 (3.23%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	1	0	1
Vitamin D deficiency
subjects affected / exposed	0 / 16 (0.00%)	0 / 31 (0.00%)	0 / 13 (0.00%)	1 / 43 (2.33%)
occurrences all number	0	0	0	1

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Were there any global substantial amendments to the protocol? Yes

22 Oct 2009

Amendment 1: Cut-off value for HIV RNA was assay added. Complete abstinence was added as an acceptable form of contraception. Grapefruit-related citrus fruits such as Seville oranges and pomelos were added to the list of concomitant medications to ensure MVC PK was not affected. Instructions for stringent liver function test monitoring were added.

16 Aug 2010

Amendment 2: ViiV Healthcare was added as the new Sponsor. Sparse PK Sampling was removed at the Early Termination Visits. It was clarified that confirmation virologic failure visit to be conducted 14-21 Days after subject withdrawal. Visit window for Isod visits changed to 1 month. Exclusion criteria for creatinine clearance was mentioned as <90 ml/min. Reference to “Sterilization” and “Post-Menopausal” was deleted. Supply of OBT was clarified. It was clarified that Isoniazid may be allowed on an individual basis and that rifampin was only allowed during Stage 2. It was clarified that an alternate method to Trofile assay could be performed if Trofile assay was not reportable. It was added that an alternate method to PhenoSense GT if result is not reportable. It was clarified that virus susceptibility to MVC would be done at the same time points as the virus susceptibility to OBT.

03 Dec 2010

Amendment 3: (Country Specific: Kenya and Uganda): It was clarified that local labs may be used for safety testing for sites in Kenya and Uganda. New safety language was addded to the AE section.

25 Feb 2011

Amendment 4: (Country Specific: Brazil): It was clarified that the Sponsor would cover the cost of OBTs if not covered under the Brazil National Program. New safety language was addded to the AE section.

01 Jun 2011

Amendment 5: Information was added to the “Subject Withdrawal” section. Exposure in Utero was renames Exposure during pregnancy and more instructions were added. Additional details were added to the “Communication of Results by Sponsor” section. The Schedule of Activities section was updated to state that the Screening Period ended on Day 1 and that the follow up period window was increased up to 1 month (this was also done elsewhere it was mentioned in the protocol). It was clarified that in the subjects who had X4 or dual/mixed tropic virus at time of failure, HIV-1 RNA and tropism would be collected at the first ISOD Follow Up visit. It was clarified that the screening BSA will be utilized for initial MVC dose. The objectives of the population PK analyses were clarified.

10 Jun 2012

Amendment 6: (Country Specific: Brazil): It was clarified that the Sponsor would cover the cost of OBTs if not covered under the Brazil National Program.

09 Aug 2012

Amendment 7: Appendix 1 was modified (Liver enzyme monitoring to be the same as other ongoing MVC studies). Appendix 5 was added (Rationale for initial MVC dose change for subjects not on potent CYP3A4 inhibitors). Appendix 6 was added (Specific for sites in Brazil). Appendix 7 was added (Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events). Changes made were aligned with CT-3: a. Reported medication error as adverse events regardless of whether it is accompanied by an AE. b. AE reporting section was updated.

30 Dec 2013

Amendment 8: The protocol was amended to extend and ensure the continued supply of the study drug beyond 5 years to subjects benefitting from therapy. It was clarified that the Sponsor would cover the cost of OBTs if it was not covered under the Brazil National Program.

19 May 2014

Amendment 9: In “Schedule of Activities” section and wherever applicable, it was a.) added that at the End of Study visit and follow-up contact, unused medications had to be returned. b.) clarified that study visits in the follow-up period would be up to Week 261. Follow up Visit 9 was added in the Schedule of Activities. The rationale was that the protocol used 52 weeks to equate to a year, however IMPALA drug management system used 48 weeks to equate to a year, resulting in a 5 month gap at the end of 5 years of follow up. c.) clarified that the window in follow-up period was updated to 14days. The rationale was to be consistent with IMPALA drug management system. d.) added that “Contraception Check” would be done at all study visits, per new protocol template. e.) added that creatinine phosphokinase, lipid profile, free T4, TSH and Hepatitis C Virus RNA from Early Termination, were done to be consistent with follow-up period.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

The Disposition section, mentioning "Overall Study" has data only for subject discontinuations up to Week 48, as the study is ongoing. The planned enrollment per protocol was 125 subjects, however, 103 subjects enrolled in the study.

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Clinical trials

Clinical Trial Results: AN OPEN-LABEL, MULTICENTER, MULTIPLE-DOSE PHARMACOKINETIC AND 48-WEEK SAFETY AND EFFICACY TRIAL OF MARAVIROC IN COMBINATION WITH OPTIMIZED BACKGROUND THERAPY FOR THE TREATMENT OF ANTIRETROVIRAL-EXPERIENCED CCR5-TROPIC HIV-1 INFECTED CHILDREN 2-18 YEARS OF AGE

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Pharmacokinetic (PK) Parameters for subjects with data in Stage 1 enrolled in Stage 2 – Week 2 and Week 48

Primary: Pharmacokinetic (PK) Parameters for subjects with data in Stage 1 enrolled in Stage 2 – Week 2 and Week 48

Primary: PK Parameters for Stage 1 subjects Enrolled in Stage 2 – Week 2 and Week 48 Results for Stage 2 doses - AUCtau (Area under the curve at steady state)

Primary: PK Parameters for Stage 1 subjects Enrolled in Stage 2 – Week 2 and Week 48 Results for Stage 2 doses - AUCtau (Area under the curve at steady state)

Primary: PK Parameters for Stage 1 subjects Enrolled in Stage 2 – Week 2 and Week 48 Results for Stage 2 doses - Tmax (Time at maximum concentration)

Primary: PK Parameters for Stage 1 subjects Enrolled in Stage 2 – Week 2 and Week 48 Results for Stage 2 doses - Tmax (Time at maximum concentration)

Primary: Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events (All Causality)

Primary: Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events (All Causality)

Primary: Treatment discontinuation secondary to Serious Adverse Event (SAE) related to study drug

Primary: Treatment discontinuation secondary to Serious Adverse Event (SAE) related to study drug

Secondary: Percentage of subjects with HIV‑1 RNA <400 copies/mL through Week 48 (MSDF)

Secondary: Percentage of subjects with HIV‑1 RNA <400 copies/mL through Week 48 (MSDF)

Secondary: Percentage of subjects with HIV‑1 RNA <48 copies/mL through Week 48 (MSDF)

Secondary: Percentage of subjects with HIV‑1 RNA <48 copies/mL through Week 48 (MSDF)

Secondary: Percentage of Subjects with HIV-1 RNA Levels <400 copies/mL at Weeks 24 and 48 using Missing, Discontinuation = Failure (MD=F) Approach

Secondary: Percentage of Subjects with HIV-1 RNA Levels <400 copies/mL at Weeks 24 and 48 using Missing, Discontinuation = Failure (MD=F) Approach

Secondary: Percentage of Subjects with HIV-1 RNA Levels < 48 copies/mL at Weeks 24 and 48 using MD=F Approach

Secondary: Percentage of Subjects with HIV-1 RNA Levels < 48 copies/mL at Weeks 24 and 48 using MD=F Approach

Secondary: Percentage of subjects with HIV-1 RNA < 400 copies/mL and <48 copies/mL using the time to loss of virologic response algorithm (TLOVR) at Week 48

Secondary: Percentage of subjects with HIV-1 RNA < 400 copies/mL and <48 copies/mL using the time to loss of virologic response algorithm (TLOVR) at Week 48

Secondary: Percentage of Subjects with >= 1.0 log10 reduction in HIV-1RNA concentration from baseline to Week 24 and Week 48

Secondary: Percentage of Subjects with >= 1.0 log10 reduction in HIV-1RNA concentration from baseline to Week 24 and Week 48

Secondary: Summary of Change from Baseline in HIV-1 RNA (Original) at Week 24 and Week 48

Secondary: Summary of Change from Baseline in HIV-1 RNA (Original) at Week 24 and Week 48

Secondary: Change from Baseline in cluster of differentiation 4 (CD4+) cell count at weeks 24 and 48

Secondary: Change from Baseline in cluster of differentiation 4 (CD4+) cell count at weeks 24 and 48

Secondary: Change from Baseline in CD4+ % at weeks 24 and 48

Secondary: Change from Baseline in CD4+ % at weeks 24 and 48

Secondary: Protocol Defined Virologic Failure

Secondary: Protocol Defined Virologic Failure

Secondary: Shift Table of Viral Tropism between Screening and Confirmed PDVF Prior to Week 48

Secondary: Shift Table of Viral Tropism between Screening and Confirmed PDVF Prior to Week 48

Secondary: Summary of the Emergence of reverse transcriptase inhibitor (RTI) and protease inhibitor (PI) resistance associated mutations (RAMs) Between Screening and On-Treatment Confirmed PDVF: Total and by Cohort Prior to Week 48

Secondary: Summary of the Emergence of reverse transcriptase inhibitor (RTI) and protease inhibitor (PI) resistance associated mutations (RAMs) Between Screening and On-Treatment Confirmed PDVF: Total and by Cohort Prior to Week 48

Secondary: Optimized Background Treatment (OBT) Susceptibility Scores (Net/Overall) by Outcome

Secondary: Optimized Background Treatment (OBT) Susceptibility Scores (Net/Overall) by Outcome

Secondary: Summary of Change from Baseline in HIV-1 RNA (Log10 copies/mL) at Week 24 and Week 48

Secondary: Summary of Change from Baseline in HIV-1 RNA (Log10 copies/mL) at Week 24 and Week 48

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
AN OPEN-LABEL, MULTICENTER, MULTIPLE-DOSE PHARMACOKINETIC AND 48-WEEK SAFETY AND EFFICACY TRIAL OF MARAVIROC IN COMBINATION WITH OPTIMIZED BACKGROUND THERAPY FOR THE TREATMENT OF ANTIRETROVIRAL-EXPERIENCED CCR5-TROPIC HIV-1 INFECTED CHILDREN 2-18 YEARS OF AGE