HIV Infections
Conditions
Keywords
Anti-HIV Agents, pentafuside
Brief summary
This study will evaluate T-20 in children.
Detailed description
Children are stratified by age group (3 through 11 years and 12 through 16 years). Samples for HIV-1 genotype and phenotype resistance testing are obtained at screening to aid in the selection of concomitant antiretrovirals. Simultaneous to initiating T-20, all patients begin a new optimized antiretroviral regimen based on the patients' prior treatment history, historical resistance testing results, and the results of the testing performed at screening. Patients are followed for safety and other assessments at Weeks 1, 2, and 4, then monthly through Week 24 and bimonthly through Week 48. Pharmacokinetic sampling at selected study visits are performed.
Interventions
DRUGEnfuvirtide
Sponsors
Trimeris
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
Patients may be eligible for this study if they: * Are 3 through 16 years of age and have the consent of parent or guardian. * Have a viral load of at least 5000 copies/ml. * Have taken at least 2 of the 3 licensed anti-HIV drug classes for at least 3 months. * Have been on stable therapy for at least 4 weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Time Curve (AUC) From 0-12 Hours for Enfuvirtide and Its Metabolite (Ro 50-6343) | Pre-dose (time 0), and 2, 4, 8, and 12 hours post-dose (Week 1) | The Area Under the Plasma Concentration-Time Curve (AUC) is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption. AUC was calculated from plasma concentration-time data (on Day 7) using standard non-compartmental pharmacokinetic methods. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximum Plasma Concentration (Tmax) for Enfuvirtide | Pre-dose (time 0), and 2, 4, 8, and 12 hours post-dose (Week 1) | Tmax is defined as actual sampling time to reach maximum observed analyte concentration. |
| Minimum Plasma Concentration (Ctrough) for Enfuvirtide and Its Metabolite (Ro 50-6343) | Pre-dose (time 0), and 2, 4, 8, and 12 hours post-dose (Week 1) | Ctrough is defined as the lowest concentration that a drug reaches before the next dose is administered. |
| AUC12h Ratio of Enfuvirtide Metabolite (Ro 50-6343)/ENF (Ro 29-9800) | Pre-dose (time 0), and 2, 4, 8, and 12 hours post-dose (Week 1) | The ratio of the area under plasma concentration-time curve from time 0 to 12 hours of Enfuvirtide Metabolite (Ro 50-6343) versus enfuvirtide was calculated. |
| Number of Participants With Adverse Events (AEs) and Serious AEs | Up to Week 4 after discontinuation of therapy | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event. |
| Maximum Plasma Concentration (Cmax) for Enfuvirtide and Its Metabolite (Ro 50-6343) | Pre-dose (time 0), and 2, 4, 8, and 12 hours post-dose (Week 1) | The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration. Cmax was calculated from plasma concentration-time data (on Day 7) using standard non-compartmental pharmacokinetic methods. |
| Number of Participants Who Died | Up to Week 96 | — |
| Number of Participants Who Prematurely Withdrew Due to AE | Up to Week 96 | — |
| Number of Participants With Worst Local Injection Site Reactions | Up to Week 96 | Numbers of Participants With worst local injection site reactions were reported. Localized injection site reactions like erythema, induration, pruritus, nodule and cyst, and ecchymosis were recorded. |
| Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | Up to Week 96 | Pediatric AIDS Clinical Trials Group (PACTG) toxicity grading scale was used for reviewing and grading clinically significant laboratory abnormalities. PACTG Grade 3 and Grade 4 were considered Severe and life threatening, respectively. |
Countries
United States
Participant flow
Recruitment details
Overall, 52 participants were enrolled in this study conducted at 16 centers in Spain and United States between 23 August 2001 and 09 December 2004.
Participants by arm
| Arm | Count |
|---|---|
| Stratum A Participants of age \>= 3 years and less than 12 years received enfuvirtide subcutaneously BID at 2.0 mg/kg per dose, up to the adult maximum of 90 mg per dose for 48 weeks. At the end of the 48 weeks of treatment, participants were allowed to continue into the extension phase and take enfuvirtide up to a maximum of an additional 48 weeks (a total of 96 weeks from study entry), or until 12 weeks after the commercial availability of enfuvirtide in the country of the participant's participation, whichever came first. | 24 |
| Stratum B Participants of age \>= 12 years and less than 17 years received enfuvirtide subcutaneously BID at 2.0 mg/kg per dose, up to the adult maximum of 90 mg per dose for 48 weeks. At the end of the 48 weeks of treatment, participants were allowed to continue into the extension phase and take enfuvirtide up to a maximum of an additional 48 weeks (a total of 96 weeks from study entry), or until 12 weeks after the commercial availability of enfuvirtide in the country of the participant's participation, whichever came first. | 28 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Admin | 3 | 2 |
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Injection Site Reactions | 0 | 2 |
| Overall Study | Insufficient Therapy | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 3 |
| Overall Study | Withdrawal by Subject | 4 | 7 |
Baseline characteristics
| Characteristic | Stratum A | Stratum B | Total |
|---|---|---|---|
| Age, Continuous | 8.7 years STANDARD_DEVIATION 1.8 | 13.9 years STANDARD_DEVIATION 1.6 | 11.5 years STANDARD_DEVIATION 3.1 |
| Sex: Female, Male Female | 15 Participants | 9 Participants | 24 Participants |
| Sex: Female, Male Male | 9 Participants | 19 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 52 / 52 |
| serious Total, serious adverse events | 31 / 52 |
Outcome results
Primary
Area Under the Plasma Concentration Time Curve (AUC) From 0-12 Hours for Enfuvirtide and Its Metabolite (Ro 50-6343)
The Area Under the Plasma Concentration-Time Curve (AUC) is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption. AUC was calculated from plasma concentration-time data (on Day 7) using standard non-compartmental pharmacokinetic methods.
Time frame: Pre-dose (time 0), and 2, 4, 8, and 12 hours post-dose (Week 1)
Population: Intensive PK Analysis Population: The first 12 participants enrolled per age group and all children aged 3 to 6 years who underwent intensive pharmacokinetic sampling at week 1 were included within the intensive PK analysis population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stratum A | Area Under the Plasma Concentration Time Curve (AUC) From 0-12 Hours for Enfuvirtide and Its Metabolite (Ro 50-6343) | Enfuvirtide | 56.1 microgram hour per milliliter (mcg.h/mL) | Standard Deviation 19.4 |
| Stratum A | Area Under the Plasma Concentration Time Curve (AUC) From 0-12 Hours for Enfuvirtide and Its Metabolite (Ro 50-6343) | Metabolite (Ro 50-6343) | 3.07 microgram hour per milliliter (mcg.h/mL) | Standard Deviation 2.77 |
| Stratum B | Area Under the Plasma Concentration Time Curve (AUC) From 0-12 Hours for Enfuvirtide and Its Metabolite (Ro 50-6343) | Enfuvirtide | 52.7 microgram hour per milliliter (mcg.h/mL) | Standard Deviation 27.4 |
| Stratum B | Area Under the Plasma Concentration Time Curve (AUC) From 0-12 Hours for Enfuvirtide and Its Metabolite (Ro 50-6343) | Metabolite (Ro 50-6343) | 3.41 microgram hour per milliliter (mcg.h/mL) | Standard Deviation 2.09 |
Secondary
AUC12h Ratio of Enfuvirtide Metabolite (Ro 50-6343)/ENF (Ro 29-9800)
The ratio of the area under plasma concentration-time curve from time 0 to 12 hours of Enfuvirtide Metabolite (Ro 50-6343) versus enfuvirtide was calculated.
Time frame: Pre-dose (time 0), and 2, 4, 8, and 12 hours post-dose (Week 1)
Population: Intensive PK Analysis Population: The first 12 participants enrolled per age group and all children aged 3 to 6 years who underwent intensive pharmacokinetic sampling at week 1 were included within the intensive PK analysis population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stratum A | AUC12h Ratio of Enfuvirtide Metabolite (Ro 50-6343)/ENF (Ro 29-9800) | 5.31 Ratio | Standard Deviation 3.55 |
| Stratum B | AUC12h Ratio of Enfuvirtide Metabolite (Ro 50-6343)/ENF (Ro 29-9800) | 7.12 Ratio | Standard Deviation 3.98 |
Secondary
Maximum Plasma Concentration (Cmax) for Enfuvirtide and Its Metabolite (Ro 50-6343)
The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration. Cmax was calculated from plasma concentration-time data (on Day 7) using standard non-compartmental pharmacokinetic methods.
Time frame: Pre-dose (time 0), and 2, 4, 8, and 12 hours post-dose (Week 1)
Population: Intensive PK Analysis Population: The first 12 participants enrolled per age group and all children aged 3 to 6 years who underwent intensive pharmacokinetic sampling at week 1 were included within the intensive PK analysis population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stratum A | Maximum Plasma Concentration (Cmax) for Enfuvirtide and Its Metabolite (Ro 50-6343) | Enfuvirtide | 6.43 mcg/mL | Standard Deviation 2.15 |
| Stratum A | Maximum Plasma Concentration (Cmax) for Enfuvirtide and Its Metabolite (Ro 50-6343) | Metabolite (Ro 50-6343) | 0.434 mcg/mL | Standard Deviation 0.667 |
| Stratum B | Maximum Plasma Concentration (Cmax) for Enfuvirtide and Its Metabolite (Ro 50-6343) | Enfuvirtide | 5.88 mcg/mL | Standard Deviation 2.81 |
| Stratum B | Maximum Plasma Concentration (Cmax) for Enfuvirtide and Its Metabolite (Ro 50-6343) | Metabolite (Ro 50-6343) | 0.450 mcg/mL | Standard Deviation 0.341 |
Secondary
Minimum Plasma Concentration (Ctrough) for Enfuvirtide and Its Metabolite (Ro 50-6343)
Ctrough is defined as the lowest concentration that a drug reaches before the next dose is administered.
Time frame: Pre-dose (time 0), and 2, 4, 8, and 12 hours post-dose (Week 1)
Population: Intensive PK Analysis Population: The first 12 participants enrolled per age group and all children aged 3 to 6 years who underwent intensive pharmacokinetic sampling at week 1 were included within the intensive PK analysis population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stratum A | Minimum Plasma Concentration (Ctrough) for Enfuvirtide and Its Metabolite (Ro 50-6343) | Enfuvirtide | 2.87 mcg/mL | Standard Deviation 1.49 |
| Stratum A | Minimum Plasma Concentration (Ctrough) for Enfuvirtide and Its Metabolite (Ro 50-6343) | Metabolite (Ro 50-6343) | 0.177 mcg/mL | Standard Deviation 0.089 |
| Stratum B | Minimum Plasma Concentration (Ctrough) for Enfuvirtide and Its Metabolite (Ro 50-6343) | Enfuvirtide | 2.98 mcg/mL | Standard Deviation 1.66 |
| Stratum B | Minimum Plasma Concentration (Ctrough) for Enfuvirtide and Its Metabolite (Ro 50-6343) | Metabolite (Ro 50-6343) | 0.242 mcg/mL | Standard Deviation 0.146 |
Secondary
Number of Participants Who Died
Time frame: Up to Week 96
Population: Safety Analysis Population: All participants who received at least one dose of study medication were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stratum A | Number of Participants Who Died | 1 participants |
| Stratum B | Number of Participants Who Died | 1 participants |
Secondary
Number of Participants Who Prematurely Withdrew Due to AE
Time frame: Up to Week 96
Population: Safety Analysis Population: All participants who received at least one dose of study medication were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stratum A | Number of Participants Who Prematurely Withdrew Due to AE | 9 participants |
| Stratum B | Number of Participants Who Prematurely Withdrew Due to AE | 17 participants |
Secondary
Number of Participants With Adverse Events (AEs) and Serious AEs
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event.
Time frame: Up to Week 4 after discontinuation of therapy
Population: Safety Analysis Population: All participants who received at least one dose of study medication were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stratum A | Number of Participants With Adverse Events (AEs) and Serious AEs | Any AE | 24 participants |
| Stratum A | Number of Participants With Adverse Events (AEs) and Serious AEs | Any SAE | 8 participants |
| Stratum B | Number of Participants With Adverse Events (AEs) and Serious AEs | Any AE | 25 participants |
| Stratum B | Number of Participants With Adverse Events (AEs) and Serious AEs | Any SAE | 15 participants |
Secondary
Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities
Pediatric AIDS Clinical Trials Group (PACTG) toxicity grading scale was used for reviewing and grading clinically significant laboratory abnormalities. PACTG Grade 3 and Grade 4 were considered Severe and life threatening, respectively.
Time frame: Up to Week 96
Population: Safety Analysis Population: All participants who received at least one dose of study medication were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stratum A | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | ALAT Grade 4 | 0 participants |
| Stratum A | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | Neutrophils Grade 4 | 1 participants |
| Stratum A | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | Total Bilirubin Grade 3 | 0 participants |
| Stratum A | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | Platelets Grade 4 | 1 participants |
| Stratum A | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | Total Bilirubin Grade 4 | 0 participants |
| Stratum A | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | ASAT Grade 3 | 2 participants |
| Stratum A | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | GGT Grade 3 | 0 participants |
| Stratum A | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | Platelets Grade 3 | 0 participants |
| Stratum A | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | GGT Grade 4 | 0 participants |
| Stratum A | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | ASAT Grade 4 | 0 participants |
| Stratum A | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | Amylase Grade 3 | 1 participants |
| Stratum A | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | Neutrophils Grade 3 | 0 participants |
| Stratum A | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | Amylase Grade 4 | 1 participants |
| Stratum A | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | ALAT Grade 3 | 1 participants |
| Stratum B | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | Amylase Grade 4 | 1 participants |
| Stratum B | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | ALAT Grade 3 | 0 participants |
| Stratum B | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | Platelets Grade 3 | 2 participants |
| Stratum B | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | Platelets Grade 4 | 0 participants |
| Stratum B | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | Neutrophils Grade 4 | 0 participants |
| Stratum B | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | ASAT Grade 3 | 0 participants |
| Stratum B | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | ASAT Grade 4 | 0 participants |
| Stratum B | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | ALAT Grade 4 | 0 participants |
| Stratum B | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | Total Bilirubin Grade 3 | 1 participants |
| Stratum B | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | Total Bilirubin Grade 4 | 0 participants |
| Stratum B | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | GGT Grade 3 | 1 participants |
| Stratum B | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | GGT Grade 4 | 0 participants |
| Stratum B | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | Amylase Grade 3 | 1 participants |
| Stratum B | Number of Participants With Treatment Emergent Grade 3 or Grade 4 Laboratory Abnormalities | Neutrophils Grade 3 | 0 participants |
Secondary
Number of Participants With Worst Local Injection Site Reactions
Numbers of Participants With worst local injection site reactions were reported. Localized injection site reactions like erythema, induration, pruritus, nodule and cyst, and ecchymosis were recorded.
Time frame: Up to Week 96
Population: Safety Analysis Population: All participants who received at least one dose of study medication were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stratum A | Number of Participants With Worst Local Injection Site Reactions | Erythema | 13 participants |
| Stratum A | Number of Participants With Worst Local Injection Site Reactions | Nodules and Cysts | 16 participants |
| Stratum A | Number of Participants With Worst Local Injection Site Reactions | Induration | 21 participants |
| Stratum A | Number of Participants With Worst Local Injection Site Reactions | Pruritus | 10 participants |
| Stratum A | Number of Participants With Worst Local Injection Site Reactions | Ecchymosis | 6 participants |
| Stratum A | Number of Participants With Worst Local Injection Site Reactions | Others | 5 participants |
| Stratum B | Number of Participants With Worst Local Injection Site Reactions | Ecchymosis | 8 participants |
| Stratum B | Number of Participants With Worst Local Injection Site Reactions | Erythema | 19 participants |
| Stratum B | Number of Participants With Worst Local Injection Site Reactions | Pruritus | 9 participants |
| Stratum B | Number of Participants With Worst Local Injection Site Reactions | Nodules and Cysts | 14 participants |
| Stratum B | Number of Participants With Worst Local Injection Site Reactions | Others | 10 participants |
| Stratum B | Number of Participants With Worst Local Injection Site Reactions | Induration | 20 participants |
Secondary
Time to Maximum Plasma Concentration (Tmax) for Enfuvirtide
Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Time frame: Pre-dose (time 0), and 2, 4, 8, and 12 hours post-dose (Week 1)
Population: Intensive PK Analysis Population: The first 12 participants enrolled per age group and all children aged 3 to 6 years who underwent intensive pharmacokinetic sampling at week 1 were included within the intensive PK analysis population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Stratum A | Time to Maximum Plasma Concentration (Tmax) for Enfuvirtide | 4.13 hour | Standard Deviation 1.35 |
| Stratum B | Time to Maximum Plasma Concentration (Tmax) for Enfuvirtide | 5.05 hour | Standard Deviation 2.67 |