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

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
3TC, TDF, NLV
Sponsored by
University of Maryland, Baltimore
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Men and women age > 18 years of age. Ability and willingness to give written informed consent. 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. Patient failed multiple treatment regimens due to development of viral resistance/and or intolerance. 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. 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. The following screening laboratory values obtained within 30 days prior to study entry: HIV-1 RNA or BDNA > 10,000 copies/mL Exclusion Criteria: Active drug or alcohol abuse or dependence which, in the opinion of the investigator, would interfere with adherence to study requirements. 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. 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). Significant Renal Insufficiency - calculated creatinine clearance < 50 Upon reviewing medication history and genotypic resistance testing, study investigators feel that would be inappropriate to enroll patient in this protocol.

Sites / Locations

  • University of Maryland Baltimore, Institute of Human Virology
  • University of Maryland, Institute of Human Virology

Outcomes

Primary Outcome Measures

Change in replication capacity over time from baseline to week 48.
Change in viral replication capacity

Secondary Outcome Measures

Change in viral load from baseline to week 48.
Change in viral load
Change in CD4 cell count from baseline to week 48.
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
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

Full Information

First Posted
June 12, 2006
Last Updated
May 6, 2021
Sponsor
University of Maryland, Baltimore
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1. Study Identification

Unique Protocol Identification Number
NCT00336778
Brief Title
Phase 1 Pilot Study of an ART Bridging Regimen in Highly Experienced Patients Unable to Achieve Viral Suppression
Official Title
A Phase I Pilot Study Of An Antiretroviral Bridging Regimen In Highly Experienced Patients Unable To Achieve Viral Suppression.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
January 2004 (undefined)
Primary Completion Date
April 2008 (Actual)
Study Completion Date
April 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Maryland, Baltimore

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
3TC, TDF, NLV
Intervention Description
3TC 300 mg PO once daily+ TDF 300 mg PO once daily+ NLV 1250 mg PO twice daily (after 12 week lead-in period)
Primary Outcome Measure Information:
Title
Change in replication capacity over time from baseline to week 48.
Description
Change in viral replication capacity
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Change in viral load from baseline to week 48.
Description
Change in viral load
Time Frame
48 weeks
Title
Change in CD4 cell count from baseline to week 48.
Description
Change in CD4
Time Frame
48 weeks
Title
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
Description
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
Time Frame
48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Men and women age > 18 years of age. Ability and willingness to give written informed consent. 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. Patient failed multiple treatment regimens due to development of viral resistance/and or intolerance. 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. 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. The following screening laboratory values obtained within 30 days prior to study entry: HIV-1 RNA or BDNA > 10,000 copies/mL Exclusion Criteria: Active drug or alcohol abuse or dependence which, in the opinion of the investigator, would interfere with adherence to study requirements. 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. 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). Significant Renal Insufficiency - calculated creatinine clearance < 50 Upon reviewing medication history and genotypic resistance testing, study investigators feel that would be inappropriate to enroll patient in this protocol.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert R Redfield, MD
Organizational Affiliation
University of Maryland, College Park
Official's Role
Study Director
Facility Information:
Facility Name
University of Maryland Baltimore, Institute of Human Virology
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
University of Maryland, Institute of Human Virology
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21210
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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