Safety Study of TXA127 to Elevate CD4+ T-Lymphocyte Counts in HIV-Infected Patients on Stable HAART Therapy

This study has been terminated.
(Difficulty recruiting subjects to dosing cohort 5.)
Sponsor:
Collaborator:
Tarix Pharmaceuticals
Information provided by (Responsible Party):
US Biotest, Inc.
ClinicalTrials.gov Identifier:
NCT00757250
First received: September 21, 2008
Last updated: February 27, 2012
Last verified: February 2012

September 21, 2008
February 27, 2012
September 2008
December 2011   (final data collection date for primary outcome measure)
HIV-1 RNA viral load count [ Time Frame: 18 weeks and 34 weeks (cohort 5) ] [ Designated as safety issue: Yes ]
HIV-1 RNA viral load count [ Time Frame: 18 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00757250 on ClinicalTrials.gov Archive Site
CD4+ T-lymphocyte count [ Time Frame: 18 weeks and 34 weeks (cohort 5) ] [ Designated as safety issue: No ]
CD4+ T-lymphocyte count [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Safety Study of TXA127 to Elevate CD4+ T-Lymphocyte Counts in HIV-Infected Patients on Stable HAART Therapy
A Phase I Evaluation of the Safety and Biologic Activity of TXA127 in HIV-Infected Subjects With CD4+ T-Lymphocyte Counts Less Than 250 Per mm3 Who Have Responded to HAART

The purpose of this study is to test the safety of an investigational medication, TXA127, and its ability to increase T-lymphocyte counts, specifically CD4+ T-lymphocytes, in persons infected with human immunodeficiency virus who are taking highly active anti-retroviral therapy.

This is a Phase I, single institution, open-label, within-dosing-cohort-schedule randomized, dose escalation study of TXA127 in HIV-infected subjects with CD4+ T-lymphocyte counts less than 250 per mm3 who have responded to highly active retroviral therapy (HAART). The study has been designed to determine the maximum tolerated dose (MTD) of TXA127 in this subject population. This study will also obtain safety and biologic activity information about the subcutaneous injection of TXA127.

Five escalating dosing cohorts will be examined to determine the MTD. The first four dosing cohorts will receive 50, 100, 200 and 300 mcg/kg of TXA127 by subcutaneous injection daily for 14 days, followed by 14 days without treatment. These 28 days will be defined as one cycle. The cycle of therapy will be repeated once, for a total of two courses of treatment. The 5th dosing cohort will receive 300 mcg/kg of TXA127 by subcutaneous injection daily for 28 days, then 14 days without treatment followed by an additional 28 days of TXA127 administration. Dose escalation to the next cohort of subjects will be permitted to the next higher dosing level provided the following criteria have been met.

A standard Simon Phase I dose escalation trial has been proposed. The MTD will have been exceeded if the proportion of subjects that develops the same or similar study-drug-related, DLT in an assigned dosing schedule equals 2/2, 2/3, 2/4, 2/5, and 2/6 subjects. The MTD is defined as the largest dose that <2 of 6 subjects experiences a DLT. Dose-limiting toxicity is defined as a study-drug-related grade 3 or 4 adverse event (AE).

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
Drug: Angiotensin 1-7
Once daily subcutaneous injection of 50, 100, 200 or 300 mcg/kg/day
Other Name: TXA127
  • Experimental: 1
    Dose Cohort 1: 50 mcg/kg/day of TXA127
    Intervention: Drug: Angiotensin 1-7
  • Experimental: 2
    Drug Cohort 2: 100 mcg/kg/day TXA127
    Intervention: Drug: Angiotensin 1-7
  • Experimental: 3
    Drug Cohort 3: 200 mcg/kg/day TXA127
    Intervention: Drug: Angiotensin 1-7
  • Experimental: 4
    Drug Cohort 4: 300 mcg/kg/day TXA127
    Intervention: Drug: Angiotensin 1-7
  • Experimental: 5
    Extended dosing cohort at 300mcg/kg TXA127 for 2 x 28-day treatment cycles, with an extended follow-up period to week 34.
    Intervention: Drug: Angiotensin 1-7
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
13
December 2011
December 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • HIV-infected males or non-pregnant, non-breast-feeding females who are >= 18 years of age;
  • CD4+ T-lymphocyte count less than 250 per mm3;
  • Successful response to HAART (defined as an HIV RNA viral load of <50 copies per mL) for a minimum of one year preceding study enrollment.

Exclusion Criteria:

  • Opportunistic infection within the 6 months prior to study enrollment
  • Active tuberculosis or other mycobacterial infection
  • Uncontrolled high blood pressure or congestive heart failure class III or IV
  • Systemic glucocorticoid or immunomodulator therapy within 30 days of study entry
  • Prior history of Kaposi's sarcoma
  • Prior history of lymphoma
  • Active substance abuse within the last 30 days
  • Uncontrolled psychiatric disorders, including depression
  • Abnormal or inadequate liver or renal function
  • Inadequate bone marrow function
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00757250
TXA127-2008-001
Yes
US Biotest, Inc.
US Biotest, Inc.
Tarix Pharmaceuticals
Study Director: Gere S diZerega, MD US Biotest, Inc.
Principal Investigator: Robert A Larsen, MD University of California, Keck School of Medicine
US Biotest, Inc.
February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP