An Open Label Pharmacokinetic, Safety And Efficacy Study Of Maraviroc In Combination With Background Therapy For The Treatment Of HIV-1 Infected, CCR5 -Tropic Children

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This open-label, multicenter, multiple dose pharmacokinetic, safety and efficacy study enrolled 103 participants at 24 sites in 8 countries.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The participants were HIV-1 infected treatment-experienced children and adolescents who were failing current antiretroviral (ARV) therapy or have failed their most recent ARV regimen, defined by plasma HIV-1 RNA>=1000 copies/mL, were infected with only R5 HIV-1, and have ARV experience/intolerance of 6 months with at least 2 ARV drug classes.

Reporting Groups

	Description
>=2 - <6 Years of Age, MVC Liquid Formulation	In cohort 1, >=2 - <6 years of age, MVC liquid formulation
>=6 - <12 Years of Age, MVC Tablet Formulation	In Cohort 2, >=6 - <12 years of age, MVC tablet formulation
>=6 - <12 Years of Age, MVC Liquid Formulation	In Cohort 3, >=6 - <12 years of age, MVC liquid formulation
>=12 - <18 Years of Age, MVC Tablet Formulation	In Cohort 4, >=12 - <18 years of age, MVC tablet formulation

Participant Flow:   Overall Study

	>=2 - <6 Years of Age, MVC Liquid Formulation	>=6 - <12 Years of Age, MVC Tablet Formulation	>=6 - <12 Years of Age, MVC Liquid Formulation	>=12 - <18 Years of Age, MVC Tablet Formulation
STARTED	16 [1]	31 [1]	13 [1]	43 [1]
COMPLETED	12	26	9	25 [2]
NOT COMPLETED	4	5	4	18
Insufficient clinical response	3	4	3	13
Adverse Event	0	0	1	1
No longer willing to participate	0	1	0	1
Non-compliance with study treatment	1	0	0	2
Blood sampling not done before Stage 1	0	0	0	1

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) consisted of all participants who received at least 1 dose of study drug (same as analysis population set [APS] 4).

Reporting Groups

	Description
>=2 - <6 Years of Age, MVC Liquid Formulation	In cohort 1, >=2 - <6 years of age, MVC liquid formulation
>=6 - <12 Years of Age, MVC Tablet Formulation	In Cohort 2, >=6 - <12 years of age, MVC tablet formulation
>=6 - <12 Years of Age, MVC Liquid Formulation	In Cohort 3, >=6 - <12 years of age, MVC liquid formulation
>=12 - <18 Years of Age, MVC Tablet Formulation	In Cohort 4, >=12 - <18 years of age, MVC tablet formulation
Total	Total of all reporting groups

Baseline Measures

	>=2 - <6 Years of Age, MVC Liquid Formulation	>=6 - <12 Years of Age, MVC Tablet Formulation	>=6 - <12 Years of Age, MVC Liquid Formulation	>=12 - <18 Years of Age, MVC Tablet Formulation	Total
Overall Participants Analyzed  [Units: Participants]	16	31	13	43	103
Age  [Units: Years] Mean (Standard Deviation)	3.4  (0.9)	9.1  (1.7)	8.9  (2.0)	14.0  (1.6)	10.3  (4.1)
Sex: Female, Male  [Units: Participants] Count of Participants
Female	5  31.3%	16  51.6%	6  46.2%	27  62.8%	54  52.4%
Male	11  68.8%	15  48.4%	7  53.8%	16  37.2%	49  47.6%

1.  Primary:

Pharmacokinetic (PK) Parameters for Participants With Data in Stage 1 Enrolled in Stage 2 – Week 48   [ Time Frame: Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose) ]

2.  Primary:

PK Parameters for Stage 1 Participants Enrolled in Stage 2 – Week 2 Results for Stage 2 Doses - AUCtau (Area Under the Curve at Steady State)   [ Time Frame: Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose) ]

3.  Primary:

PK Parameters for Stage 1 Participants Enrolled in Stage 2 – Week 2 Results for Stage 2 Doses - Tmax (Time at Maximum Concentration)   [ Time Frame: Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose) ]

4.  Primary:

Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events (All Causality)   [ Time Frame: 48 weeks ]

5.  Primary:

Treatment Discontinuation Secondary to Serious Adverse Event (SAE) Related to Study Drug   [ Time Frame: Week 48 ]

6.  Secondary:

Percentage of Participants With HIV‑1 RNA <400 Copies/mL Through Week 48 (MSDF)   [ Time Frame: Week 24 and Week 48 post-treatment. ]

7.  Secondary:

Percentage of Participants With HIV‑1 RNA <48 Copies/mL Through Week 48 (MSDF)   [ Time Frame: Week 24 and Week 48 post-treatment ]

8.  Secondary:

Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL at Weeks 24 and 48 Using Missing, Discontinuation = Failure (MD=F)Approach   [ Time Frame: Week 24 and Week 48 post-treatment ]

9.  Secondary:

Percentage of Participants With HIV-1 RNA Levels < 48 Copies/mL at Weeks 24 and 48 Using MD=F Approach   [ Time Frame: Week 24 and Week 48 post-treatment ]

10.  Secondary:

Percentage of Participants With HIV-1 RNA <400 Copies/mL and <48 Copies/mL Using the Time to Loss of Virologic Response Algorithm (TLOVR) at Week 48   [ Time Frame: Week 48 ]

11.  Secondary:

Percentage of Participants With >= 1.0 log10 Reduction in HIV-1RNA Concentration From Baseline to Week 24 and Week 48   [ Time Frame: Week 24 and Week 48 post-treatment ]

12.  Secondary:

Summary of Change From Baseline in HIV-1 RNA (Original) by Visit   [ Time Frame: Week 24 and Week 48 post-treatment ]

13.  Secondary:

Summary of Change From Baseline in HIV-1 RNA (Log10 Copies/mL) by Visit   [ Time Frame: Week 24 and Week 48 post-treatment ]

14.  Secondary:

Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count at Weeks 24 and 48   [ Time Frame: Week 24 and Week 48 post-treatment ]

15.  Secondary:

Change From Baseline in CD4+ Percent (%) at Weeks 24 and 48   [ Time Frame: Week 24 and Week 48 post-treatment ]

16.  Secondary:

Protocol Defined Virologic Failure   [ Time Frame: Week 48 ]

17.  Secondary:

Shift Table of Viral Tropism Between Screening and Confirmed PDVF Prior to Week 48   [ Time Frame: Screening and Week 48 ]

18.  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   [ Time Frame: 48 weeks ]

19.  Secondary:

Optimized Background Treatment (OBT) Susceptibility Scores (Net/Overall) by Outcome   [ Time Frame: 48 weeks ]

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Although the Participant Flow Table title indicates "Overall Study", the data presented in that table is Subject Discontinuations Through Week 48. The study is ongoing.