Clinical trial NCT00344760: A Study to Evaluate of the Efficacy of Enfuvirtide During the Induction Phase of Therapy
Official title: Viral Decay Kinetics During Induction Therapy With or Without the Use of Enfuvirtide in HAART-naÃ-ve Patients With Advanced HIV
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
First posted: 2006-06-27
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: We hypothesize that using a potent antiretroviral such as Enfuvirtide during the induction phase of HAART therapy will lead to faster clearance of virus and infected cells, and lower number of minority variant HIV-1 strains.

Detailed description: This is an 48 week Phase 4, open label, randomized, prospective, pilot proof of concept study to evaluate the use of Enfuvirtide in an induction/maintenance treatment model. Patients meeting inclusion criteria will be stratified into two groups according to HIV-1 RNA viral loads (less than 300,000 copies/ml and greater than 300,000 copies/ml). Thereafter, patients will be block randomized (the size of each block will be two patients) into one of two treatment arms.

All patients will receive Efavirenz 600mg once a day, Lamivudine 300 mg once a day, and Tenofovir 300mg once a day. After randomization, one half of the patients will receive no additional treatment, while the other half will receive Enfuvirtide 90mg sq BID until the viral load is \<50 x 2 consecutive visits or 12 weeks (whichever comes first).

Eligibility criteria: Inclusion Criteria:

1. Age: 18 to 70 years of age.
2. Sex: Male or Female.
3. Documented HIV-1 seropositive by Western Blot, Elisa, or HIV-1 viral load.
4. Naïve to HAART.
5. Viral load \>100,000c/ml.
6. CD4\<200c/ml.
7. Volunteers must be willing and able to provide written informed consent to participate in the study.
8. Available for at least 48 weeks of follow-up.

Exclusion Criteria:

1. Volunteers with an acute and clinically significant medical event as determined by the investigator to result in a life expectancy less then 12 months despite ART.
2. Volunteers with current psychiatric illness, alcohol abuse or illicit drug use that in the opinion of the Principal Investigator may interfere with patient's ability to comply with protocol requirements.
3. Renal insufficiency (Estimated Creatinine clearance of \<60ml/min.)
4. Patients with malabsorption or severe chronic diarrhea for more than 30 days.
5. Inability to consume adequate oral intake (defined as inability to eat at least 1 meal per day).
6. Current treatment for malignancy other than basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
7. Any other medical condition which, in the opinion of the investigator, might interfere with completion of the study or evaluation of the results.
8. Pregnancy or breastfeeding
9. In a female capable of child bearing, unwillingness to use effective barrier contraception or abstinence
10. Patient who is currently receiving an experimental medication.

Primary outcomes:
measure: Time to viral suppression below 50c/ml.
timeFrame: Individual
Secondary outcomes:
measure: Log viral copy/ml decrease over time during phase 1 and phase 2.
timeFrame: Over the 48 week study period
measure: Development of clinical mutations.
timeFrame: Over the 48 week study period
measure: Development of sub-clinical mutations (minority variants)
timeFrame: Over the 48 week study period
measure: Viral suppression (below 50c/ml) at 24 and 48 weeks.
timeFrame: At 24 and 48 weeks
measure: Time to loss of viral response. Loss of viral response defined as:
timeFrame: Over the 48 week study period
measure: Less then 2.0 log decrease in viral load at week 8.
timeFrame: Week 8
measure: Inability to achieve Viral load <50c/ml by week 12.
timeFrame: Week 12
measure: Viral load >50c/ml on 2 consecutive measurements taken 2 weeks apart after viral
timeFrame: Over the 48 week study period
measure: suppression <50c/ml has occurred
timeFrame: Over the 48 week study period
measure: Rate and quantity of HIV-1 proviral DNA decay.
timeFrame: Over the 48 week study period
measure: Safety and tolerability.
timeFrame: Over the 48 week study period
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland, Institute of Human Virology
state: Maryland
Study officials:
affiliation: University of Maryland, School of Medicine, Department of Infectious Disease
name: Ronald B Reisler, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: