Clinical trial NCT00021554: T-20 in HIV Patients With Prior Drug Treatment and/or Resistance to Each of the Three Classes of Anti-HIV Drugs
Official title: A Phase III Open-Label, Randomized, Active-Controlled Study Assessing the Efficacy and Safety of T-20 (HIV-1 Fusion Inhibitor) in Combination With an Optimized Background Regimen, Versus Optimized Background Regimen Alone, in Patients With Prior Experience and/or Prior Documented Resistance to Each of the Three Classes of Approved Antiretrovirals (Nucleoside Reverse Transcriptase, Non-Nucleoside Reverse Transcriptase and Protease Inhibitors)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: HIV-1
Drug Therapy, Combination
HIV Protease Inhibitors
RNA, Viral
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Viral Load
pentafuside
Lead sponsor: NIH AIDS Clinical Trials Information Service
Sponsor class: INDUSTRY
Collaborators: name: Trimeris
First posted: 2001-08-31
Enrollment: 525
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to show if a dose of T-20 added to an anti-HIV combination (chosen specifically for each patient) lowers viral load by at least a certain level after 24 weeks as compared to an anti-HIV combination (chosen specifically for each patient) alone. Another purpose is to show if the patient response to T-20 will be maintained for 48 weeks.

Detailed description: An OB regimen is selected to be initiated at baseline by the physician and patient. The OB regimen is based on the patient's prior treatment history as well as the results from the first screening visit HIV-1 genotypic and phenotypic (GT and PT) resistance testing and prior GT/PT antiretroviral resistance testing (if available). Prior or current laboratory abnormalities, including triglycerides and cholesterol, should also be taken into account when selecting the OB regimen. Patients are stratified with respect to the following: 1) screening viral load (less than 40,000 or 40,000 or more copies/ml); and 2) number of allowed investigational antiretrovirals (0, 1, or 2). Patients then are randomized to receive 1 of the following treatments for 48 weeks: OB regimen or OB plus T-20 regimen. Patients are seen for evaluation of efficacy and safety at Weeks 1, 2, and 4, every 4 weeks through Week 24, and then every 8 weeks through Week 48. In addition, efficacy only is evaluated at Weeks 6, 10, and 14. Patients also may be seen at additional visits during the study for plasma HIV-1 RNA measurements to potentially confirm virological failure.

Patients initially randomized to the OB arm who meet the criteria for virological failure and who switch to OB plus T-20 after Week 8 are followed under a new ("switch") schedule of assessments. Patients are encouraged to change their OB regimen at the time of switch.

Patients initially randomized to the OB plus T-20 arm who meet the criteria for virological failure may continue to receive OB plus T-20 if the patient and the physician feel that there is sufficient benefit. Patients are encouraged to change their OB regimen after Week 8 if they choose to continue on OB plus T-20 despite meeting the criteria for virological failure.

Patients on OB or OB plus T-20 arm who meet the criteria for virological failure but who do not wish to either switch to T-20 (for patients initially randomized to OB arm) or continue with T-20 (for patients initially randomized to OB plus T-20) are allowed to remain in the study for a maximum of 1 month.

At the end of the 48 weeks of treatment, patients are allowed to participate in 1 of the following treatment extensions: a) roll-over and receive OB plus T-20 (for patients receiving OB alone); or b) continue taking OB plus T-20 (for patients already receiving OB plus T-20), for a maximum of an additional 48 weeks (plus 4 weeks safety follow-up period), or until 12 weeks after commercial availability of T-20 in the country in which they are treated, whichever comes first. All patients are followed for a maximum of 100 weeks from their initial baseline visit date.

Eligibility criteria: Inclusion Criteria

Patients may be eligible for this study if they:

* Are HIV infected.
* Are at least 16 years of age.
* Have an HIV-1 RNA of at least 5,000 copies/ml.
* Have received anti-HIV drugs for at least 3 months and/or have written records of resistance to at least 1 member of each of the 3 classes of anti-HIV drugs (nucleoside reverse transcriptase inhibitors \[NRTIs\], nonnucleoside reverse transcriptase inhibitors \[NNRTIs\], and protease inhibitors \[PIs\]). Resistance to NNRTIs may not be required in certain cases.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Carlton
country: Australia
facility: Carlton Clinic
city: Darlinghurst
country: Australia
facility: Holdsworth House General Practice
city: Darlinghurst
country: Australia
facility: Saint Vincent's Hosp
city: Herston
country: Australia
facility: Royal Brisbane Hosp
city: Prahan
country: Australia
facility: Alfred Hosp
city: South Yarra
country: Australia
facility: Prahran Market Clinic
city: Sydney
country: Australia
facility: Taylors Square Clinic
city: Antwerpe
country: Belgium
facility: Inst of Tropical Medicine
city: Brussels
country: Belgium
facility: CHU Saint Pierre
city: Leuven
country: Belgium
facility: UZ Gasthuisberg
city: Bonn
country: Germany
facility: Rheinische Friedrich Wilhelms Universitaet Medizinische
city: Frankfurt
country: Germany
facility: Klinikum Der Johann Wolfgang Goethe Universitat
city: Hamburg
country: Germany
facility: Allgemeines Krankenhaus St Georg
city: Hamburg
country: Germany
facility: Universitatskrankenhaus Eppendorf
city: Firenze
country: Italy
facility: UO Malattie Infettive
city: Milano
country: Italy
facility: Clinica Malattie Infettive
city: Torino
country: Italy
facility: Ospedale Amedeo di Savoia
city: Amsterdam
country: Netherlands
facility: Natac Med Centre
city: CX Utrecht
country: Netherlands
facility: Univ Medical Center Utrecht
city: Barcelona
country: Spain
facility: Hospital Germans Trias I Pujol
city: Madrid
country: Spain
facility: Hosp La Paz
city: Valencia
country: Spain
facility: Hospital General Universitario
city: Malmoe
country: Sweden
facility: University Hospital Mas
city: Stockholm
country: Sweden
facility: Karolinska Hospital
city: Stockholm
country: Sweden
facility: Venhalsan Soder Hosp
city: Basel
country: Switzerland
facility: Univ Hosp Basel / Med Outpatient Dept
city: Geneve
country: Switzerland
facility: Hopital cantonal / Div des maladies infectieuses
city: Lausanne
country: Switzerland
facility: CHUV
city: Zurich
country: Switzerland
facility: Universitatsspital Zurich
city: Brighton
country: United Kingdom
facility: Brighton Gen Hosp
city: Edinburgh
country: United Kingdom
facility: Western Gen Hosp
city: Liverpool
country: United Kingdom
facility: Royal Liverpool Univ Hosp
city: London
country: United Kingdom
facility: Chelsea and Westminster Hosp
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Royal Free Hosp
city: London
country: United Kingdom
facility: Univ College London Med School
city: Manchester
country: United Kingdom
facility: North Manchester Gen Hosp
Study officials:
References:
citation: Lazzarin A, Clotet B, Cooper D, Reynes J, Arasteh K, Nelson M, Katlama C, Stellbrink HJ, Delfraissy JF, Lange J, Huson L, DeMasi R, Wat C, Delehanty J, Drobnes C, Salgo M; TORO 2 Study Group. Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia. N Engl J Med. 2003 May 29;348(22):2186-95. doi: 10.1056/NEJMoa035211.