A Study to Evaluate of the Efficacy of Enfuvirtide During the Induction Phase of Therapy

Phase 4

Completed

• Conditions: HIV Infections
• Interventions: Drug: Efavirenz, lamivudine, and tenofovir; Drug: Enfuvirtide

• Registration Number: NCT00344760
• Lead Sponsor: University of Maryland, Baltimore

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).

Study Timeline

• Study Start: 2005-01
• Study First Submitted: 2006-06-23
• Study First Submitted QC: 2006-06-23
• Study First Posted: 2006-06-27
• Primary Completion: 2007-03
• Study Completion: 2007-03
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-06
• Last Update Posted: 2021-05-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard Treatment	Efavirenz, lamivudine, and tenofovir	Efavirenz 600mg once daily, Lamivudine 300mg once daily and Tenofovir 300mg once daily
Standard Treatment Plus Enfuvirtide	Enfuvirtide	Efavirenz 600mg once daily, Lamivudine 300mg once daily, Tenofovir 300mg once daily and enfuvirtide 90mg subcutaneously twice a day until the viral load is less than 50copies for 2 consecutive visits or 12 weeks (whichever comes first).
Standard Treatment Plus Enfuvirtide	Efavirenz, lamivudine, and tenofovir	Efavirenz 600mg once daily, Lamivudine 300mg once daily, Tenofovir 300mg once daily and enfuvirtide 90mg subcutaneously twice a day until the viral load is less than 50copies for 2 consecutive visits or 12 weeks (whichever comes first).

Primary Outcome Measures

Name	Time	Method
Time to viral suppression below 50c/ml.	Individual	The study is 48 weeks long and the time to viraL suppression will vary depending on the subject. Or there is the possibility that they do not supress

Secondary Outcome Measures

Name	Time	Method
Less then 2.0 log decrease in viral load at week 8.	Week 8
Inability to achieve Viral load <50c/ml by week 12.	Week 12
Log viral copy/ml decrease over time during phase 1 and phase 2.	Over the 48 week study period
Time to loss of viral response. Loss of viral response defined as:	Over the 48 week study period
Development of clinical mutations.	Over the 48 week study period
Development of sub-clinical mutations (minority variants)	Over the 48 week study period
Viral suppression (below 50c/ml) at 24 and 48 weeks.	At 24 and 48 weeks
Viral load >50c/ml on 2 consecutive measurements taken 2 weeks apart after viral	Over the 48 week study period
suppression <50c/ml has occurred	Over the 48 week study period
Rate and quantity of HIV-1 proviral DNA decay.	Over the 48 week study period
Safety and tolerability.	Over the 48 week study period

Trial Locations

Locations (1)

University of Maryland, Institute of Human Virology; 🇺🇸 Baltimore, Maryland, United States