HIV Infections
Conditions
Keywords
Treatment Experienced
Brief summary
This 2-arm study evaluated the efficacy and safety of Fuzeon with an integrase inhibitor in an expanded access program plus an optimized background antiviral regimen (AVR) in HIV-1 infected patients naive to Fuzeon and an integrase inhibitor. In the first cohort phase of the study (Phase I), eligible patients received Fuzeon 90 mg subcutaneously (SC) twice daily until confirmation of response (min/max = 8/16 weeks). In Phase II, the randomised comparator phase of the study, responders were randomized to receive Fuzeon either 90 mg SC twice a day or 180 mg SC once a day for a further 16 weeks. Non-responders and virological failures were terminated from the study. The anticipated time on study treatment was 3-9 months, and the target sample size was 210 individuals.
Interventions
90 mg SC twice daily
DRUGOptimized background ARV
As prescribed
As prescribed
Sponsors
Trimeris
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients, \>=18 years of age * HIV-1 infection * Triple class treatment-experienced, Fuzeon- and integrase-inhibitor naive * GSS \>= 3 ; nucleosides excluded
Exclusion criteria
* Adverse clinical or laboratory experience \>ACTG Grade 4 * Untreated infection, intercurrent illness, drug toxicity or other condition contraindicating an antiretroviral regimen * Malignancy requiring chemotherapy or radiotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients in Phase I of the Study With a Confirmed HIV-1 RNA Viral Load ≤ 50 Copies/mL | Between Week I-4 and Week I-12 of Phase I of the study | Virologic responders were defined as patients who had an initial HIV-1 RNA assessment \<= 50 copies/mL during Phase I at any visit between Week I-4 and Week I-12 and a confirmatory viral load assessment ≤ 50 copies/mL at the next visit (Week I-8 to Week II-16) |
| Number of Patients in Phase II of the Study With HIV-1 RNA ≤ 50 Copies/mL at Week II-16 | Week II-16 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Virologic Response Over Time in Phase II of the Study | Weeks II-4, 8, 12 & 16 | The number of intent-to-treat (ITT) participants with HIV-1 RNA \<= 50 copies/mL and HIV-1 RNA \< 400 copies/mL by study week. |
| Virologic Response Over Time in Phase I of the Study | Weeks 4, 8 & 12 | The number of intent-to-treat (ITT) participants with HIV-1 RNA \<= 50 copies/mL and HIV-1 RNA \< 400 copies/mL by study week are summarized below. |
| Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Phase I and II | — |
| CD4+ Lymphocyte Count Change From Baseline | Phase I Baseline and Phase II Weeks II-1, 12, 16, and LOCF | Change from study Phase I baseline in CD4+ lymphocyte count at Phase II study Weeks II - 1, 12, 16, and LOCF by treatment arm. Change from study Phase II baseline in CD4+ lymphocyte count at Phase II study weeks II - 12 and 16. |
| HIV-1 RNA Viral Load Change From Baseline in Phase I of the Study | Baseline and Weeks 4, 8, 12 & LOCF | Change from baseline in HIV-1 RNA (log10 copies/mL) at study Weeks I-4, 8, 12 & LOCF for ITT patients in Phase I of the study |
Countries
Puerto Rico, United States
Participant flow
Pre-assignment details
Phase I of the study was a single group. In Phase II of the study, the remaining patients were randomized to either the enfuvirtide (90 mg) BID group or the enfuvirtide (180 mg) QD group.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: ENF 90mg SC BID (Phase 1: ENF 90mg SC BID): In the first phase or cohort phase of day I-1 through Week I-12 of the trial all patients received enfuvirtide (ENF) 90 mg subcutaneously (SC) twice daily (BID) + Isentress® \[raltegravir\] (RAL) 400-mg orally (PO) BID + optimized background (OB) with at least 1 fully active antiretroviral (ARV) agent excluding nucleoside reverse transcriptase inhibitor (NRTIs). | 29 |
| Total | 29 |
Baseline characteristics
| Characteristic | Phase 1: ENF 90mg SC BID |
|---|---|
| Age Continuous | 45.4 years STANDARD_DEVIATION 10.3 |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 29 | 0 / 9 | 0 / 5 |
| serious Total, serious adverse events | 4 / 29 | 0 / 9 | 0 / 5 |
Outcome results
Primary
Number of Patients in Phase II of the Study With HIV-1 RNA ≤ 50 Copies/mL at Week II-16
Time frame: Week II-16
Population: Intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I: ENF 90mg SC BID | Number of Patients in Phase II of the Study With HIV-1 RNA ≤ 50 Copies/mL at Week II-16 | 5 participants |
| Phase II Arm B: Phase I Then ENF 180mg SC QD | Number of Patients in Phase II of the Study With HIV-1 RNA ≤ 50 Copies/mL at Week II-16 | 3 participants |
Primary
Number of Patients in Phase I of the Study With a Confirmed HIV-1 RNA Viral Load ≤ 50 Copies/mL
Virologic responders were defined as patients who had an initial HIV-1 RNA assessment \<= 50 copies/mL during Phase I at any visit between Week I-4 and Week I-12 and a confirmatory viral load assessment ≤ 50 copies/mL at the next visit (Week I-8 to Week II-16)
Time frame: Between Week I-4 and Week I-12 of Phase I of the study
Population: Intent-to-treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: ENF 90mg SC BID | Number of Patients in Phase I of the Study With a Confirmed HIV-1 RNA Viral Load ≤ 50 Copies/mL | Week 8 | 8 participants |
| Phase I: ENF 90mg SC BID | Number of Patients in Phase I of the Study With a Confirmed HIV-1 RNA Viral Load ≤ 50 Copies/mL | Week 12 | 5 participants |
| Phase I: ENF 90mg SC BID | Number of Patients in Phase I of the Study With a Confirmed HIV-1 RNA Viral Load ≤ 50 Copies/mL | Week 16 | 1 participants |
Secondary
CD4+ Lymphocyte Count Change From Baseline
Change from study Phase I baseline in CD4+ lymphocyte count at Phase II study Weeks II - 1, 12, 16, and LOCF by treatment arm. Change from study Phase II baseline in CD4+ lymphocyte count at Phase II study weeks II - 12 and 16.
Time frame: Phase I Baseline and Phase II Weeks II-1, 12, 16, and LOCF
Population: Intent-to-treat
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase I: ENF 90mg SC BID | CD4+ Lymphocyte Count Change From Baseline | Phase I baseline to Week 1 of Phase II (n=8,5) | 22 cells/mm3 |
| Phase I: ENF 90mg SC BID | CD4+ Lymphocyte Count Change From Baseline | Phase I baseline to Week 16 of Phase II (n=6,4) | 61.0 cells/mm3 |
| Phase I: ENF 90mg SC BID | CD4+ Lymphocyte Count Change From Baseline | Phase I baseline to Week 12 of Phase II (n=7,4) | 83.0 cells/mm3 |
| Phase II Arm B: Phase I Then ENF 180mg SC QD | CD4+ Lymphocyte Count Change From Baseline | Phase I baseline to Week 1 of Phase II (n=8,5) | 118.0 cells/mm3 |
| Phase II Arm B: Phase I Then ENF 180mg SC QD | CD4+ Lymphocyte Count Change From Baseline | Phase I baseline to Week 16 of Phase II (n=6,4) | 179.0 cells/mm3 |
| Phase II Arm B: Phase I Then ENF 180mg SC QD | CD4+ Lymphocyte Count Change From Baseline | Phase I baseline to Week 12 of Phase II (n=7,4) | 174.5 cells/mm3 |
Secondary
HIV-1 RNA Viral Load Change From Baseline in Phase I of the Study
Change from baseline in HIV-1 RNA (log10 copies/mL) at study Weeks I-4, 8, 12 & LOCF for ITT patients in Phase I of the study
Time frame: Baseline and Weeks 4, 8, 12 & LOCF
Population: Intent-to-treat population. Last Observation Carried Forward (LOCF) includes non-missing data values from the last post-baseline visit for each participant which was carried forward to impute missing data values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: ENF 90mg SC BID | HIV-1 RNA Viral Load Change From Baseline in Phase I of the Study | Baseline (N=29) | 4.4 log10 copies/mL | Standard Deviation 0.87 |
| Phase I: ENF 90mg SC BID | HIV-1 RNA Viral Load Change From Baseline in Phase I of the Study | change at Week 4 (n=27) | 2.1 log10 copies/mL | Standard Deviation 0.46 |
| Phase I: ENF 90mg SC BID | HIV-1 RNA Viral Load Change From Baseline in Phase I of the Study | change at Week 8 (n=24) | 2.0 log10 copies/mL | Standard Deviation 0.81 |
| Phase I: ENF 90mg SC BID | HIV-1 RNA Viral Load Change From Baseline in Phase I of the Study | change at Week 12 (n=14) | 2.4 log10 copies/mL | Standard Deviation 1.09 |
| Phase I: ENF 90mg SC BID | HIV-1 RNA Viral Load Change From Baseline in Phase I of the Study | change at Week 16 (n=10) | 2.3 log10 copies/mL | Standard Deviation 0.9 |
| Phase I: ENF 90mg SC BID | HIV-1 RNA Viral Load Change From Baseline in Phase I of the Study | change at LOCF (n=27) | 1.9 log10 copies/mL | Standard Deviation 0.61 |
Secondary
Percentage of Patients With Ongoing Injection Site Reactions (ISRs)
Time frame: Phase I and II
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: ENF 90mg SC BID | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Pruritus | 44 Percentage of patients |
| Phase I: ENF 90mg SC BID | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Nodules | 56 Percentage of patients |
| Phase I: ENF 90mg SC BID | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Ecchymosis | 40 Percentage of patients |
| Phase I: ENF 90mg SC BID | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Erythema | 80 Percentage of patients |
| Phase I: ENF 90mg SC BID | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Any type | 92 Percentage of patients |
| Phase I: ENF 90mg SC BID | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Induration | 80 Percentage of patients |
| Phase I: ENF 90mg SC BID | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Pain/discomfort | 52 Percentage of patients |
| Phase II Arm B: Phase I Then ENF 180mg SC QD | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Pruritus | 28.6 Percentage of patients |
| Phase II Arm B: Phase I Then ENF 180mg SC QD | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Erythema | 71.4 Percentage of patients |
| Phase II Arm B: Phase I Then ENF 180mg SC QD | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Nodules | 57.1 Percentage of patients |
| Phase II Arm B: Phase I Then ENF 180mg SC QD | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Pain/discomfort | 42.9 Percentage of patients |
| Phase II Arm B: Phase I Then ENF 180mg SC QD | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Induration | 100 Percentage of patients |
| Phase II Arm B: Phase I Then ENF 180mg SC QD | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Ecchymosis | 14.3 Percentage of patients |
| Phase II Arm B: Phase I Then ENF 180mg SC QD | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Any type | 100 Percentage of patients |
| Phase II - Arm B | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Ecchymosis | 20 Percentage of patients |
| Phase II - Arm B | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Any type | 100 Percentage of patients |
| Phase II - Arm B | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Pain/discomfort | 60 Percentage of patients |
| Phase II - Arm B | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Erythema | 100 Percentage of patients |
| Phase II - Arm B | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Induration | 100 Percentage of patients |
| Phase II - Arm B | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Nodules | 80 Percentage of patients |
| Phase II - Arm B | Percentage of Patients With Ongoing Injection Site Reactions (ISRs) | Pruritus | 20 Percentage of patients |
Secondary
Virologic Response Over Time in Phase II of the Study
The number of intent-to-treat (ITT) participants with HIV-1 RNA \<= 50 copies/mL and HIV-1 RNA \< 400 copies/mL by study week.
Time frame: Weeks II-4, 8, 12 & 16
Population: intent-to-treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: ENF 90mg SC BID | Virologic Response Over Time in Phase II of the Study | Week 12 (< 400 copies/mL) | 7 participants |
| Phase I: ENF 90mg SC BID | Virologic Response Over Time in Phase II of the Study | Week 8 (< 400 copies/mL) | 7 participants |
| Phase I: ENF 90mg SC BID | Virologic Response Over Time in Phase II of the Study | Week 4 (< 400 copies/mL) | 6 participants |
| Phase I: ENF 90mg SC BID | Virologic Response Over Time in Phase II of the Study | Week 12 (<= 50 copies/mL) | 6 participants |
| Phase I: ENF 90mg SC BID | Virologic Response Over Time in Phase II of the Study | Week 16 (<= 50 copies/mL) | 5 participants |
| Phase I: ENF 90mg SC BID | Virologic Response Over Time in Phase II of the Study | Week 4 (<= 50 copies/mL) | 5 participants |
| Phase I: ENF 90mg SC BID | Virologic Response Over Time in Phase II of the Study | Week 16 (< 400 copies/mL) | 6 participants |
| Phase I: ENF 90mg SC BID | Virologic Response Over Time in Phase II of the Study | Week 8 (<= 50 copies/mL) | 6 participants |
| Phase II Arm B: Phase I Then ENF 180mg SC QD | Virologic Response Over Time in Phase II of the Study | Week 16 (< 400 copies/mL) | 4 participants |
| Phase II Arm B: Phase I Then ENF 180mg SC QD | Virologic Response Over Time in Phase II of the Study | Week 12 (< 400 copies/mL) | 4 participants |
| Phase II Arm B: Phase I Then ENF 180mg SC QD | Virologic Response Over Time in Phase II of the Study | Week 4 (<= 50 copies/mL) | 4 participants |
| Phase II Arm B: Phase I Then ENF 180mg SC QD | Virologic Response Over Time in Phase II of the Study | Week 4 (< 400 copies/mL) | 4 participants |
| Phase II Arm B: Phase I Then ENF 180mg SC QD | Virologic Response Over Time in Phase II of the Study | Week 8 (<= 50 copies/mL) | 4 participants |
| Phase II Arm B: Phase I Then ENF 180mg SC QD | Virologic Response Over Time in Phase II of the Study | Week 8 (< 400 copies/mL) | 4 participants |
| Phase II Arm B: Phase I Then ENF 180mg SC QD | Virologic Response Over Time in Phase II of the Study | Week 16 (<= 50 copies/mL) | 3 participants |
| Phase II Arm B: Phase I Then ENF 180mg SC QD | Virologic Response Over Time in Phase II of the Study | Week 12 (<= 50 copies/mL) | 4 participants |
Secondary
Virologic Response Over Time in Phase I of the Study
The number of intent-to-treat (ITT) participants with HIV-1 RNA \<= 50 copies/mL and HIV-1 RNA \< 400 copies/mL by study week are summarized below.
Time frame: Weeks 4, 8 & 12
Population: Intent-to-treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: ENF 90mg SC BID | Virologic Response Over Time in Phase I of the Study | Week 4 (<= 50 copies/mL) | 11 participants |
| Phase I: ENF 90mg SC BID | Virologic Response Over Time in Phase I of the Study | Week 4 (< 400 copies/mL) | 22 participants |
| Phase I: ENF 90mg SC BID | Virologic Response Over Time in Phase I of the Study | Week 8 (<= 50 copies/mL) | 14 participants |
| Phase I: ENF 90mg SC BID | Virologic Response Over Time in Phase I of the Study | Week 8 (< 400 copies/mL) | 22 participants |
| Phase I: ENF 90mg SC BID | Virologic Response Over Time in Phase I of the Study | Week 12 (<= 50 copies/mL) | 14 participants |
| Phase I: ENF 90mg SC BID | Virologic Response Over Time in Phase I of the Study | Week 12 (< 400 copies/mL) | 19 participants |