Phase 1 Pilot Study of an ART Bridging Regimen in Highly Experienced Patients Unable to Achieve Viral Suppression

This study has been completed.
Sponsor:
Information provided by:
University of Maryland
ClinicalTrials.gov Identifier:
NCT00336778
First received: June 12, 2006
Last updated: May 21, 2010
Last verified: May 2010
  Purpose

We hypothesize that a simple bridging ARV regimen that tends to select for virus with a low replicative capacity may tend to stabilize CD4 cell counts and HIV viral load and might be an option to consider in patients with MDR HIV.

This strategy will provide them with the bridge they desperately need so that they can await the development of new therapies that when used in combination will give them the best chance in achieving complete virologic suppression.


Condition Intervention Phase
HIV Infections
Drug: 3TC, TDF, NLV
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Pilot Study Of An Antiretroviral Bridging Regimen In Highly Experienced Patients Unable To Achieve Viral Suppression.

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • Change in replication capacity over time from baseline to week 48. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Change in viral replication capacity


Secondary Outcome Measures:
  • Change in viral load from baseline to week 48. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Change in viral load

  • Change in CD4 cell count from baseline to week 48. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Change in CD4

  • Time to first Grade 3 sign, symptom, or lab abnormality,and/or OI that is at least a grade higher than baseline or a significant increase in viral load from baseline or a greater than 50% decline in CD4 cell count [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    Grade 3 sign, symptom, lab abnormality, OI that has exacerbated. Or a significant increase in viral load from baseline or a greater than 50% decline in CD4


Enrollment: 6
Study Start Date: January 2004
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: 3TC, TDF, NLV
    3TC 300 mg PO once daily+ TDF 300 mg PO once daily+ NLV 1250 mg PO twice daily (after 12 week lead-in period)
Detailed Description:

Bridge is a pilot, single-arm, open-label, study to assess the ability of 3 FDA approved anti-retroviral drugs to decrease replication capacity of HIV virus in order to stabilize CD4 cell count and HIV RNA viral loads . All subjects will be prescribed the three-drug combination of lamivudine (3TC) + tenofovir disoproxil fumarate (TDF) + nelfinavir (NLV)The "Bridge Study" is a pilot, study to assess the ability of 3 FDA approved anti-retroviral drugs to decrease replication capacity of HIV virus in order to stabilize CD4 cell count and HIV RNA viral loads. All subjects will receive the three-drug combination of lamivudine (3TC)+tenofovir disoproxil fumarate(TDF)+nelfinavir (NLV)

The study will enroll 12 subjects for a 48 week study. Major entry criteria include: HIV+ Men and women 18 years of age who are currently failing antiretroviral(ARV)therapy with an HIV-1 RNA VL > 10,000 and have failed multiple treatment regimens due to resistance and/or intolerance. Genotype must demonstrate resistance to 3 major classes of ARV's - PI's, NNRTI's, and NRTI's.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men and women age > 18 years of age.
  2. Ability and willingness to give written informed consent.
  3. HIV-1 infection as documented by any licensed ELISA test kit and confirmed by either Western blot, HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA prior to study entry.
  4. Patient failed multiple treatment regimens due to development of viral resistance/and or intolerance.
  5. Patient's provider feels that patient has exhausted currently available treatment options and that it is highly unlikely that a regimen (including one that contains T-20) could be constructed that would result in sustained virologic suppression at this time.
  6. Evidence of MDR virus (broad 3 class resistance) based on the results of the MDR-HIV qualifying screening genotypic resistance test or a history of a previous genotypic resistance test.
  7. The following screening laboratory values obtained within 30 days prior to study entry:

    • HIV-1 RNA or BDNA > 10,000 copies/mL

Exclusion Criteria:

  1. Active drug or alcohol abuse or dependence which, in the opinion of the investigator, would interfere with adherence to study requirements.
  2. History of any illness that, in the opinion of the study investigators, might confound the results of the study or pose additional risk in administering study drugs to the subject.
  3. Acute therapy for a serious infection or other serious medical illnesses that are potentially life threatening and require systemic therapy and/or hospitalization.

    NOTE: Subjects with a serious infection or serious medical illness must complete acute therapy at least 7 days prior to study entry. Subjects with all other infections or medical illnesses (e.g., vaginitis, folliculitis, bronchitis, pharyngitis, thrush) must receive appropriate therapy prior to study entry (no time restriction).

  4. Significant Renal Insufficiency - calculated creatinine clearance < 50
  5. Upon reviewing medication history and genotypic resistance testing, study investigators feel that would be inappropriate to enroll patient in this protocol.
  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: NCT00336778

Locations
United States, Maryland
University of Maryland, Institute of Human Virology
Baltimore, Maryland, United States, 21210
University of Maryland Baltimore, Institute of Human Virology
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
University of Maryland
Investigators
Study Director: Robert R Redfield, MD University of Maryland
  More Information

No publications provided

Responsible Party: Dr. Robert R. Redfield, Institute of Human Virology
ClinicalTrials.gov Identifier: NCT00336778     History of Changes
Other Study ID Numbers: H-22675
Study First Received: June 12, 2006
Last Updated: May 21, 2010
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on September 15, 2014