HIV Infection
Conditions
Brief summary
This multicenter, open-label, noncomparative study evaluates two oral formulations of raltegravir (MK-0518, film-coated tablet and chewable tablet) in combination with other antiretroviral agents for safety, tolerability, and antiretroviral activity in treatment-naive or treatment-experienced Russian children and adolescents infected with human immunodeficiency virus-1 (HIV-1). As raltegravir is indicated in combination with other antiretroviral therapies (ARTs) for the treatment of HIV-1 infection in pediatric patients in the United States (US), this study is designed to gain local treatment experience on the use of raltegravir in the pediatric HIV-infected population in Russia.
Interventions
DRUGRaltegravir Film-coated Tablet
DRUGOther Anti-Retroviral Therapy
At baseline, the investigator selected the other anti-retroviral therapies to be used in combination with raltegravir based on current treatment guidelines, the participant's treatment history, and prior anti-retroviral resistance testing
Sponsors
Covance
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* HIV positive * Weight of at least 7 kg * HIV RNA ≥1000 copies/mL within 45 days before study treatment * Participants of reproductive potential and sexually active agree to remain abstinent or use (or have their partner use) an acceptable method of birth control throughout the study.
Exclusion criteria
* Females pregnant or breast-feeding, or expecting to conceive or donate eggs during the study; males planning to impregnate or provide sperm donation during the study * Use of any non-antiretroviral (ART) investigational agents within one month before study treatment * Current (active) diagnosis of acute hepatitis or chronic hepatitis other than stable chronic Hepatitis B and/or C * Prior or current use of raltegravir * Use of another experimental HIV-integrase inhibitor * History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study, or interfere with participation for the full duration of the study * Requires or is anticipated to require any prohibited medications * Use of immunosuppressive therapy within 30 days before beginning raltegravir study treatment; short courses of corticosteroids are permitted. * History of malignancy * Current treatment for active tuberculosis infection * Use of recreational or illicit drugs or a recent history (within the last year) of drug or alcohol abuse or dependence
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least One Clinical Adverse Experience | Up to Week 26 | A clinical adverse experience is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an adverse experience. |
| Percentage of Participants Who Discontinued Study Treatment Due to a Clinical Adverse Experience | Up to Week 24 | A clinical adverse experience is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an adverse experience. |
| Percentage of Participants With at Least One Laboratory Adverse Experience | Up to Week 26 | A laboratory adverse experience is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an adverse experience. |
| Percentage of Participants Who Discontinued Study Treatment Due to a Laboratory Adverse Experience | Up to Week 24 | A laboratory adverse experience is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an adverse experience. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count | Baseline and Week 24 | This outcome is a measure of immunological response to treatment |
| Percentage of Participants Achieving HIV RNA <200 Copies/mL | Week 24 | This outcome is a measure of virological (anti-retroviral) response to treatment. Plasma HIV RNA was measured using the Abbott RealTime HIV-1 assay, which has a linear range of 40 HIV RNA copies/mL to 10 million HIV RNA copies/mL |
| Change From Baseline in CD4 Cell Percentage | Baseline and Week 24 | This outcome is a measure of immunological response to treatment |
| Percentage of Participants Achieving >=1 log10 Reduction From Baseline in Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) or Had an HIV RNA Assessment of <200 Copies/mL | Week 24 | This outcome is a measure of virological (anti-retroviral) response to treatment. Plasma HIV RNA was measured using the Abbott RealTime HIV-1 assay, which has a linear range of 40 HIV RNA copies/mL to 10 million HIV RNA copies/mL |
| Percentage of Participants Achieving HIV RNA <40 Copies/mL | Week 24 | This outcome is a measure of virological (anti-retroviral) response to treatment. Plasma HIV RNA was measured using the Abbott RealTime HIV-1 assay, which has a linear range of 40 HIV RNA copies/mL to 10 million HIV RNA copies/mL |
Participant flow
Pre-assignment details
Film-coated tablets were administered to participants \>=12 years old and to those 6 to \<12 years old who weighed \>=25 kg and could swallow pills. A weight-based dose of chewable tablets was administered to participants 6 to \<12 years old who could not swallow pills or preferred the chewable formulation, and to participants 2 to \<6 years old
Participants by arm
| Arm | Count |
|---|---|
| Raltegravir Film-coated Tablet Raltegravir film-coated tablet 400 mg administered orally twice-daily, in combination with other anti-retroviral therapy for 24 weeks. | 4 |
| Raltegravir Chewable Tablet Raltegravir chewable tablet weight-based dose up to 300 mg administered orally twice-daily, in combination with other anti-retroviral therapy for 24 weeks | 28 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Raltegravir Chewable Tablet | Raltegravir Film-coated Tablet |
|---|---|---|---|
| Age, Customized 12 to <18 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Customized 2 to <6 years | 11 Participants | 11 Participants | 0 Participants |
| Age, Customized 6 to <12 years | 19 Participants | 17 Participants | 2 Participants |
| Sex: Female, Male Female | 17 Participants | 16 Participants | 1 Participants |
| Sex: Female, Male Male | 15 Participants | 12 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 4 | 8 / 28 |
| serious Total, serious adverse events | 0 / 4 | 0 / 28 |
Outcome results
Primary
Percentage of Participants Who Discontinued Study Treatment Due to a Clinical Adverse Experience
A clinical adverse experience is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an adverse experience.
Time frame: Up to Week 24
Population: All patients as treated population included all enrolled participants who received at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Raltegravir Film-coated Tablet | Percentage of Participants Who Discontinued Study Treatment Due to a Clinical Adverse Experience | 0.0 Percentage of participants |
| Raltegravir Chewable Tablet | Percentage of Participants Who Discontinued Study Treatment Due to a Clinical Adverse Experience | 0.0 Percentage of participants |
Primary
Percentage of Participants Who Discontinued Study Treatment Due to a Laboratory Adverse Experience
A laboratory adverse experience is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an adverse experience.
Time frame: Up to Week 24
Population: All patients as treated population included all enrolled participants who received at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Raltegravir Film-coated Tablet | Percentage of Participants Who Discontinued Study Treatment Due to a Laboratory Adverse Experience | 0.0 Percentage of participants |
| Raltegravir Chewable Tablet | Percentage of Participants Who Discontinued Study Treatment Due to a Laboratory Adverse Experience | 0.0 Percentage of participants |
Primary
Percentage of Participants With at Least One Clinical Adverse Experience
A clinical adverse experience is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an adverse experience.
Time frame: Up to Week 26
Population: All patients as treated population included all enrolled participants who received at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Raltegravir Film-coated Tablet | Percentage of Participants With at Least One Clinical Adverse Experience | 0.0 Percentage of participants |
| Raltegravir Chewable Tablet | Percentage of Participants With at Least One Clinical Adverse Experience | 42.9 Percentage of participants |
Primary
Percentage of Participants With at Least One Laboratory Adverse Experience
A laboratory adverse experience is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an adverse experience.
Time frame: Up to Week 26
Population: All patients as treated population included all enrolled participants who received at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Raltegravir Film-coated Tablet | Percentage of Participants With at Least One Laboratory Adverse Experience | 0.0 Percentage of participants |
| Raltegravir Chewable Tablet | Percentage of Participants With at Least One Laboratory Adverse Experience | 3.6 Percentage of participants |
Secondary
Change From Baseline in CD4 Cell Percentage
This outcome is a measure of immunological response to treatment
Time frame: Baseline and Week 24
Population: The population analyzed included all participants who received at least one dose of study drug, had baseline evaluation (required for change from baseline endpoints only), and had Week 24 evaluation
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Raltegravir Film-coated Tablet | Change From Baseline in CD4 Cell Percentage | 4.0 Percentage change |
| Raltegravir Chewable Tablet | Change From Baseline in CD4 Cell Percentage | 6.0 Percentage change |
Secondary
Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count
This outcome is a measure of immunological response to treatment
Time frame: Baseline and Week 24
Population: The population analyzed included all participants who received at least one dose of study drug, had baseline evaluation (required for change from baseline endpoints only), and had Week 24 evaluation
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Raltegravir Film-coated Tablet | Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count | 30.3 cells/mm^3 |
| Raltegravir Chewable Tablet | Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count | 296.3 cells/mm^3 |
Secondary
Percentage of Participants Achieving >=1 log10 Reduction From Baseline in Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) or Had an HIV RNA Assessment of <200 Copies/mL
This outcome is a measure of virological (anti-retroviral) response to treatment. Plasma HIV RNA was measured using the Abbott RealTime HIV-1 assay, which has a linear range of 40 HIV RNA copies/mL to 10 million HIV RNA copies/mL
Time frame: Week 24
Population: Full analysis set included all participants who received at least one dose of study drug, had baseline evaluation (required for change from baseline endpoints only), and had at least one postbaseline evaluation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Raltegravir Film-coated Tablet | Percentage of Participants Achieving >=1 log10 Reduction From Baseline in Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) or Had an HIV RNA Assessment of <200 Copies/mL | 75.0 Percentage of participants |
| Raltegravir Chewable Tablet | Percentage of Participants Achieving >=1 log10 Reduction From Baseline in Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) or Had an HIV RNA Assessment of <200 Copies/mL | 88.0 Percentage of participants |
Secondary
Percentage of Participants Achieving HIV RNA <200 Copies/mL
This outcome is a measure of virological (anti-retroviral) response to treatment. Plasma HIV RNA was measured using the Abbott RealTime HIV-1 assay, which has a linear range of 40 HIV RNA copies/mL to 10 million HIV RNA copies/mL
Time frame: Week 24
Population: Full analysis set included all participants who received at least one dose of study drug, had baseline evaluation, and had at least one postbaseline evaluation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Raltegravir Film-coated Tablet | Percentage of Participants Achieving HIV RNA <200 Copies/mL | 50.0 Percentage of participants |
| Raltegravir Chewable Tablet | Percentage of Participants Achieving HIV RNA <200 Copies/mL | 76.0 Percentage of participants |
Secondary
Percentage of Participants Achieving HIV RNA <40 Copies/mL
This outcome is a measure of virological (anti-retroviral) response to treatment. Plasma HIV RNA was measured using the Abbott RealTime HIV-1 assay, which has a linear range of 40 HIV RNA copies/mL to 10 million HIV RNA copies/mL
Time frame: Week 24
Population: Full analysis set included all participants who received at least one dose of study drug, had baseline evaluation, and had at least one postbaseline evaluation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Raltegravir Film-coated Tablet | Percentage of Participants Achieving HIV RNA <40 Copies/mL | 50.0 Percentage of participants |
| Raltegravir Chewable Tablet | Percentage of Participants Achieving HIV RNA <40 Copies/mL | 44.0 Percentage of participants |