A Study to Evaluate of the Efficacy of Enfuvirtide During the Induction Phase of Therapy - Full Text View

Purpose

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.

Condition	Intervention	Phase
HIV Infections	Drug: Enfuvirtide Drug: Efavirenz, lamivudine, and tenofovir	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Viral Decay Kinetics During Induction Therapy With or Without the Use of Enfuvirtide in HAART-naÃ-ve Patients With Advanced HIV

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Lamivudine Tenofovir Efavirenz Enfuvirtide Tenofovir Disoproxil Fumarate

U.S. FDA Resources

Further study details as provided by University of Maryland:

Primary Outcome Measures:

Time to viral suppression below 50c/ml. [ Time Frame: Individual ] [ Designated as safety issue: No ]
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:

Log viral copy/ml decrease over time during phase 1 and phase 2. [ Time Frame: Over the 48 week study period ] [ Designated as safety issue: No ]
Development of clinical mutations. [ Time Frame: Over the 48 week study period ] [ Designated as safety issue: Yes ]
Development of sub-clinical mutations (minority variants) [ Time Frame: Over the 48 week study period ] [ Designated as safety issue: Yes ]
Viral suppression (below 50c/ml) at 24 and 48 weeks. [ Time Frame: At 24 and 48 weeks ] [ Designated as safety issue: Yes ]
Time to loss of viral response. Loss of viral response defined as: [ Time Frame: Over the 48 week study period ] [ Designated as safety issue: Yes ]
Less then 2.0 log decrease in viral load at week 8. [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
Inability to achieve Viral load <50c/ml by week 12. [ Time Frame: Week 12 ] [ Designated as safety issue: Yes ]
Viral load >50c/ml on 2 consecutive measurements taken 2 weeks apart after viral [ Time Frame: Over the 48 week study period ] [ Designated as safety issue: Yes ]
suppression <50c/ml has occurred [ Time Frame: Over the 48 week study period ] [ Designated as safety issue: Yes ]
Rate and quantity of HIV-1 proviral DNA decay. [ Time Frame: Over the 48 week study period ] [ Designated as safety issue: Yes ]
Safety and tolerability. [ Time Frame: Over the 48 week study period ] [ Designated as safety issue: Yes ]


Estimated Enrollment:	2
Study Start Date:	January 2005
Study Completion Date:	March 2007
Primary Completion Date:	March 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Standard Treatment Efavirenz 600mg once daily, Lamivudine 300mg once daily and Tenofovir 300mg once daily	Drug: Efavirenz, lamivudine, and tenofovir Efavirenz -600mg once daily, lamivudine- 300mg once daily, and tenofovir 300mg once daily Other Name: Atripla, Epivir and Viread
Experimental: Standard Treatment Plus 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).	Drug: Enfuvirtide subcutaneously twice a day Other Name: Fuzeon (T-20) Drug: Efavirenz, lamivudine, and tenofovir Efavirenz -600mg once daily, lamivudine- 300mg once daily, and tenofovir 300mg once daily Other Name: Atripla, Epivir and Viread

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


Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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.
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.
Renal insufficiency (Estimated Creatinine clearance of <60ml/min.)
Patients with malabsorption or severe chronic diarrhea for more than 30 days.
Inability to consume adequate oral intake (defined as inability to eat at least 1 meal per day).
Current treatment for malignancy other than basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
Any other medical condition which, in the opinion of the investigator, might interfere with completion of the study or evaluation of the results.
Pregnancy or breastfeeding
In a female capable of child bearing, unwillingness to use effective barrier contraception or abstinence
Patient who is currently receiving an experimental medication.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00344760

Locations


United States, Maryland
University of Maryland, Institute of Human Virology
Baltimore, Maryland, United States, 21201

Sponsors and Collaborators

University of Maryland

Investigators


Principal Investigator:	Ronald B Reisler, MD, MPH	University of Maryland, School of Medicine, Department of Infectious Disease

More Information


Responsible Party:	Dr. Ronald Reisler, Institute of Human Virology
ClinicalTrials.gov Identifier:	NCT00344760 History of Changes
Other Study ID Numbers:	H-26280
Study First Received:	June 23, 2006
Last Updated:	February 7, 2013
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Tenofovir Lamivudine Efavirenz Enfuvirtide Antiviral Agents Anti-Infective Agents	Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Anti-HIV Agents Cytochrome P-450 CYP2C9 Inhibitors Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 CYP2C19 Inhibitors Cytochrome P-450 CYP2B6 Inducers Cytochrome P-450 Enzyme Inducers Cytochrome P-450 CYP3A Inducers HIV Fusion Inhibitors Viral Fusion Protein Inhibitors

HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Tenofovir
Lamivudine
Efavirenz
Enfuvirtide
Antiviral Agents
Anti-Infective Agents

Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers
HIV Fusion Inhibitors
Viral Fusion Protein Inhibitors

ClinicalTrials.gov processed this record on September 28, 2016