BLQ Study: A Study of a Protease Inhibitor With Fuzeon (Enfuvirtide) in Treatment-Experienced Patients With HIV-1.

Study Overview
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Brief Summary
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This single arm study will evaluate the efficacy, safety and tolerability of a new investigational protease inhibitor (PI) plus background antiretrovirals plus Fuzeon (90mg sc bid) in HIV-1 infected, triple-class treatment-experienced, Fuzeon-naive adults. The new investigational PI will be administered according to the procedures of the early access program in which the patient is enrolled. The anticipated time on study treatment is 3-12 months, and the target sample size is approximately 120 individuals.

Official Title
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A Multicenter, Open-label Study Evaluating the Safety and Efficacy of a New Protease Inhibitor (Darunavir) With Fuzeon® (Enfuvirtide) Plus Background Antiretroviral Regimen in HIV-1 Infected, Triple-class Treatment-experienced Patients

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Background ARVs
* Drug: PI
* Drug: enfuvirtide [Fuzeon]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >=18 years of age; seropositive for HIV-1; enrolled in an early access program for a new investigational PI; naive to Fuzeon, and the investigational PI; treatment-experienced with 3 ARV classes of drug (NRTI, NNRTI and PI). Exclusion Criteria: females who are pregnant or breast-feeding; evidence of active, untreated opportunistic infection; malignancy requiring chemotherapy or radiotherapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enfuvirtide+PI+ARV's<br>Eligible participants received Fuzeon® (enfuvirtide) 90 milligram (mg) subcutaneously (SC) two times a day (bid) for 24 weeks plus new protease inhibitor (PI) (darunavir/ritonavir) plus other investigator-choice antiretrovirals (ARVs). Participants selected their preferred injection device among the following three options: 27 gauge (G) ½ needle/syringe, 31G 8 millimeter (mm) needle/syringe or Biojector 2000 (B2000) needle-free injection device (NFID). | Drug: Background ARVs<br>* As prescribed<br>Drug: PI<br>* As prescribed<br>Drug: enfuvirtide [Fuzeon]<br>* 90mg sc bid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Viral Load <50 Copies/mL | Blood samples for HIV-1 RNA viral load measurement were collected at the Week 24 clinic visit. The number of participants with HIV-1 RNA viral load results <50 copies/mL is reported. | Week 24 | 
| Percentage of Participants With HIV-1 RNA Viral Load <50 Copies/mL | Blood samples for HIV-1 RNA viral load measurement were collected at the Week 24 clinic visit. The percentage of participants with HIV-1 RNA results <50 copies/mL is reported. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With HIV-1 RNA Viral Load <50 Copies/mL | Blood samples for HIV-1 RNA viral load measurement were collected at the Week 4 and Week 12 clinic visit. The number of participants with HIV-1 RNA results <50 copies/mL is reported. | Week 4 and 12 | 
| Percentage of Participants With HIV-1 RNA Viral Load <50 Copies/mL | Blood samples for HIV-1 RNA viral load measurement were collected at the Week 4 and Week 12 clinic visit. The percentage of participants with HIV-1 RNA Viral Load results <50 copies/mL is reported. | Week 4 and 12 | 
| Number of Participants With HIV-1 RNA Viral Load <400 Copies/mL | Blood samples for HIV-1 RNA viral load measurement were collected at the Week 4, Week 12, and Week 24 clinic visit. The number of participants with HIV-1 RNA Viral Load results <400 copies/mL is reported. | Weeks 4, 12, and 24 | 
| Percentage of Participants With HIV-1 RNA Viral Load <400 Copies/mL | Blood samples for HIV-1 RNA viral load measurement were collected at the Week 4, Week 12, and Week 24 clinic visit. The number of participants with HIV-1 RNA Viral Load results <400 copies/mL is reported. | Weeks 4, 12, and 24 | 
| Change From Baseline in Log 10 Plasma HIV-1 RNA Viral Load | Summary statistics for change from baseline in plasma HIV-1 RNA count were presented. Change from baseline in plasma HIV-1 RNA count was derived as follows: Change from baseline = (plasma HIV-1 RNA count at Week X) - (plasma HIV-1 RNA count at baseline). | Baseline (Day 1), Weeks 4, 12, and 24 | 
| Number of Participants With Any Adverse Event (AE) and Serious Adverse Event (SAE) | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAEs are defined as those events that were fatal or immediately life-threatening, and those events that resulted in hospitalization; prolonged an existing hospitalization; resulted in disability; or was a congenital anomaly. | Up to Week 28 | 
| Change From Baseline in CD4+ Lymphocyte Count | Summary statistics for change from baseline in CD4+ lymphocyte count were presented . Change from baseline in CD4+ lymphocyte count was derived as follows: Change from baseline = (CD4+ count at Week X) - (CD4+ count at baseline). | Baseline (Day 1), Weeks 4, 12, and 24 | 
| Number of Participants Meeting Virologic Failure Criteria | The participant was considered as virologic failure at Week 12 clinic visit if patient achieved HIV-RNA <50 copies/mL at Week 4, and HIV-RNA > 50 copies/mL at Week 12, and HIV-RNA >50 copies/mL confirmed at 2 to 4 weeks after Week 12 or if participants failed to achieve a viral load decrease from baseline greater or equal to 0.5 log10 at Week 12 and failed to achieve a viral load decrease from baseline greater or equal to 0.5 log10 confirmed at 2 to 4 weeks after Week 12. The participant was considered as virologic failure at Week 24 clinic visit if participant achieved HIV-RNA <50 copies/mL at week 12, and HIV-RNA >50 copies/mL at week 24/early discontinuation, and HIV-RNA >50 copies/mL confirmed at 2 to 4 weeks after week 24/early discontinuation or HIV-RNA >50 copies/mL at any time up to week 24 and HIV-RNA >50 copies/mL confirmed at 2 to 4 weeks after week 24/early discontinuation. | Weeks 12 and 24 | 
| Percentage of Participants Meeting Virologic Failure Criteria | The participant was considered as virologic failure at Week 12 clinic visit if patient achieved HIV-RNA <50 copies/mL at Week 4, and HIV-RNA > 50 copies/mL at Week 12, and HIV-RNA >50 copies/mL confirmed at 2 to 4 weeks after Week 12 or if participants failed to achieve a viral load decrease from baseline greater or equal to 0.5 log10 at Week 12 and failed to achieve a viral load decrease from baseline greater or equal to 0.5 log10 confirmed at 2 to 4 weeks after Week 12. The participant was considered as virologic failure at Week 24 clinic visit if participant achieved HIV-RNA <50 copies/mL at week 12, and HIV-RNA >50 copies/mL at week 24/early discontinuation, and HIV-RNA >50 copies/mL confirmed at 2 to 4 weeks after week 24/early discontinuation or HIV-RNA >50 copies/mL at any time up to week 24 and HIV-RNA >50 copies/mL confirmed at 2 to 4 weeks after week 24/early discontinuation. | Weeks 12 and 24 | 
| Number of Participants Adhering to Enfuvirtide (ENF) | Adherence to ENF treatment regimen was calculated using the participant's response to the query on the Participant Adherence Questionnaire case report form (CRF) about injections incomplete or missed in the last 4 days preceding the study visit. The percentage adherence to the ENF regimen at each study visit is given by: % Adherence = ([8 - the number of doses missed] / 8) x 100. The number and percentage of participants adhering to the ENF regimen were presented by adherence category (100%, ≥95%, ≥90% and ≥85%) at Weeks 4, 12, and 24. | Weeks 4, 12, and 24 | 
| Percentage of Participants Adhering to ENF | Adherence to ENF treatment regimen was calculated using the participant's response to the query on the Participant Adherence Questionnaire case report form (CRF) about injections incomplete or missed in the last 4 days preceding the study visit. The percentage adherence to the ENF regimen at each study visit is given by: % Adherence = ([8 - the number of doses missed] / 8) x 100. The number and percentage of participants adhering to the ENF regimen were presented by adherence category (100%, ≥95%, ≥90% and ≥85%) at Weeks 4, 12, and 24. | Weeks 4, 12, and 24 | 
| Number of Participants With 1 or More Injection Site Reactions Meeting the Criteria of an Serious Adverse Event | Injection site reactions (ISRs) referred to any localized sign or symptom, including erythema, induration, pruritus, nodules, ecchymosis (degree of bruising/ discoloration), and pain/discomfort. Injection site reactions were monitored by trained study personnel at weeks 1, 4, 12, 16, and 24. Interruption of ENF for toxicity management of recurrent local grade 3 or 4 ISRs until the sign or symptom resolved to grade 2 was at the discretion of the investigator. Any individual injection site signs or symptoms meeting the criteria for a serious adverse event (SAE) had to be reported as an SAE. In the event of a serious ISR, the participant was to immediately discontinue ENF and withdraw from the study. If the participant was not already hospitalized, serious ISRs required a clinic visit within 72 hours of the event. | Week 1 to Week 24 | 
| Percentage of Participants With 1 or More Injection Site Reactions Meeting the Criteria of an Serious Adverse Event | Injection site reactions (ISRs) referred to any localized sign or symptom, including erythema, induration, pruritus, nodules, ecchymosis (degree of bruising/ discoloration), and pain/discomfort. Injection site reactions were monitored by trained study personnel at weeks 1, 4, 12, 16, and 24. Interruption of ENF for toxicity management of recurrent local grade 3 or 4 ISRs until the sign or symptom resolved to grade 2 was at the discretion of the investigator. Any individual injection site signs or symptoms meeting the criteria for a serious adverse event (SAE) had to be reported as an SAE. In the event of a serious ISR, the participant was to immediately discontinue ENF and withdraw from the study. If the participant was not already hospitalized, serious ISRs required a clinic visit within 72 hours of the event. | Week 1 to Week 24 | 
| Descriptive Summary of ISR Parameters (ie, Severity and Frequency of Pain and Symptoms) by Injection Device Based on an ISR Grading Tool. | Injection site reactions (ISRs) referred to any localized sign or symptom, including erythema, induration, pruritus, nodules, ecchymosis (degree of bruising/ discoloration), and pain/discomfort. Injection site reactions were monitored by trained study personnel at weeks 1, 4, 12, 16, and 24. Grades 0 through 4 are a measure of intensity, not seriousness. Thus, a grade 3 or grade 4 sign or symptom could be severe, but not necessarily serious. Only active, ongoing ISR were counted. The maximum severity grade for pain/discomfort since the last visit at any injection site was recorded whether or not the maximum severity of pain/discomfort was ongoing at the time of clinical evaluation. | Week 24 | 
| Number of Participants Discontinuing Study Medication Due to Clinical Adverse Events | The total number and percentage of participants who discontinued the study medication (ENF) due to clinical adverse events (including clinically significant laboratory abnormalities and AIDS Clinical Trials Group (ACTG) grade≥3 laboratory toxicities) were noted and presented. | Up to Week 24 |