Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Angiotensin 1-7
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by US Biotest, Inc.:

Primary Outcome Measures:
  • HIV-1 RNA viral load count [ Time Frame: 18 weeks and 34 weeks (cohort 5) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • CD4+ T-lymphocyte count [ Time Frame: 18 weeks and 34 weeks (cohort 5) ] [ Designated as safety issue: No ]

Enrollment: 13
Study Start Date: September 2008
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Dose Cohort 1: 50 mcg/kg/day of TXA127
Drug: Angiotensin 1-7
Once daily subcutaneous injection of 50, 100, 200 or 300 mcg/kg/day
Other Name: TXA127
Experimental: 2
Drug Cohort 2: 100 mcg/kg/day TXA127
Drug: Angiotensin 1-7
Once daily subcutaneous injection of 50, 100, 200 or 300 mcg/kg/day
Other Name: TXA127
Experimental: 3
Drug Cohort 3: 200 mcg/kg/day TXA127
Drug: Angiotensin 1-7
Once daily subcutaneous injection of 50, 100, 200 or 300 mcg/kg/day
Other Name: TXA127
Experimental: 4
Drug Cohort 4: 300 mcg/kg/day TXA127
Drug: Angiotensin 1-7
Once daily subcutaneous injection of 50, 100, 200 or 300 mcg/kg/day
Other Name: TXA127
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.
Drug: Angiotensin 1-7
Once daily subcutaneous injection of 50, 100, 200 or 300 mcg/kg/day
Other Name: TXA127

Detailed Description:

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).

  Eligibility

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

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
  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: NCT00757250

Locations
United States, California
LAC+USC Medical Center, Rand Schrader Clini
Los Angeles, California, United States, 90033
UCSD Division of Infectious Diseases
San Diego, California, United States, 92103
Harbor - UCLA Medical Center
Torrance, California, United States, 90502
Sponsors and Collaborators
US Biotest, Inc.
Tarix Pharmaceuticals
Investigators
Study Director: Gere S diZerega, MD US Biotest, Inc.
Principal Investigator: Robert A Larsen, MD University of California, Keck School of Medicine
  More Information

No publications provided

Responsible Party: US Biotest, Inc.
ClinicalTrials.gov Identifier: NCT00757250     History of Changes
Other Study ID Numbers: TXA127-2008-001
Study First Received: September 21, 2008
Last Updated: February 27, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by US Biotest, Inc.:
HIV
AIDS
Human Immunodeficiency Virus
CD4+ T-lymphocytes
treatment Experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Angiotensin I (1-7)
Antihypertensive Agents
Cardiovascular Agents
Pharmacologic Actions
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on November 20, 2014