AMD11070 in HIV Infections and X4 Tropic Virus - Clinical Trials Registry

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Drug: AMD11070

Detailed Description

AMD11070 is a new chemical entity that inhibits HIV-1 entry by binding specifically and reversibly to CXCR4, a coreceptor required by T-tropic virus for membrane fusion and entry into cells. The purpose of this study is to evaluate the safety and relative antiretroviral activity of AMD11070 in HIV-infected individuals who have demonstrated X4 -tropic virus in their plasma. With the ongoing development of other fusion and entry inhibitors and the need for alternative treatment options in patients (especially those with multidrug resistant virus), the demonstration of activity and safety of AMD11070 represents a potentially important advance in antiretroviral therapeutics. This will be the first study that determines the therapeutic potential of anti-CXCR4 compounds in HIV-infected patients.

Note: Study was previously suspended due to non-clinical reports of hepatotoxicity and histologic findings. Study has been completed.

Study Type

Interventional

Enrollment (Actual)

10

Phase

Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United Kingdom
- - London, United Kingdom, SW10 9TH
United States
- Florida
  - Orlando, Florida, United States, 32803

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

HIV-1 infection, as documented by any licensed ELISA test kit (confirmed by Western Blot), HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, cDNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.
Both antiretroviral treatment-naïve and -experienced patients. Treatment-experienced patients currently on antiretroviral therapy are required to have a washout period of at least 14 days prior to study entry.
Presence of X4 tropic virus as determined by a luciferase activity of ≥2000 rlu on the HIV-1 coreceptor tropism assay from a sample collected no more than 56 days prior to study baseline.
Peripheral blood CD4+ cell count ≤200 cells/mm^3.
Plasma HIV-1 RNA ≥5000 copies/ml by any standard assay.
Laboratory values prior to study entry: A. Absolute neutrophil count (ANC) ≥750/mm^3. B. WBC ≥1500/mm^3. C. Hemoglobin ≥10g/dL. D. Platelet count ≥80,000/mm^3. E. Creatinine ≤ 1.2 x ULN. F. AST (SGOT), ALT (SGPT), and alkaline phosphatase ≤ 1.5 x ULN. G. Total bilirubin ≤ 1.2 x ULN. Note: Except for patients who are on atazanavir or indinavir during screening. For these patients, total bilirubin ≤ 4.0 x ULN will be permitted. H. Serum lipase within normal limits. I. PT and PTT ≤ 1.2 x ULN. J. Calcium and magnesium within normal limits.
Female patients of reproductive potential must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/ml performed within 24 hours before study entry and initiation of the protocol-specified medication..
All patients must agree not to participate in the conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization).
Willingness of female patients to discontinue hormonal contraception 1 week prior to study entry. Note: Female patients who discontinue hormonal contraception prior to study entry may resume hormonal contraception after study day 11.
Karnofsky performance score ≥90 at screening.
Ability and willingness of patient or legal guardian/representative to give written informed consent.

Exclusion Criteria:

Patients with a known sensitivity to AMD11070 and its excipients (cellulose, croscarmellose, sodium stearyl fumarate, silicone dioxide, calcium phosphate dihydrate,sodium lauryl sulfate).
Pregnancy or breast-feeding.
Any antiretroviral treatment within 14 days prior to study entry.
Any immunizations within 30 days prior to study entry.
Treatment with radiation therapy or cytotoxic chemotherapy agents or immuno-modulating agents within 30 days prior to study entry.
Use of contraindicated prescription medications, herbal supplements, or aspirin within seven days prior to study entry.
Use of any CYP-3A4 inhibitors or inducers, and P-gp inducers and inhibitors. Use of CYP-450 substrates are allowed in the protocol with the exception of CYP-2D6 and CYP-2C8 substrates.
Use of any investigational drug (i.e. drugs not approved for any indication) within 30 days prior to study entry.
Evidence of active infection or acute illness of any kind within 14 days prior to study entry,including HIV-associated opportunistic infection.
Chronic diarrhea defined as >3 stools/day for more than 4 weeks prior to study entry.
Documented history of cardiac conduction abnormalities, cardiac arrhythmias, or cardiomyopathy, any repolarization delay (QTc >500msec) or a history of additional risk factors for torsade de pointes (e.g., heart failure, hypokalemia).
Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
Any other medical or psychological condition that might, in the opinion of the site investigator, interfere with participation in the study or put the patients at undue risk.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: TREATMENT
Allocation: NA
Interventional Model: SINGLE_GROUP
Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
safety and antiviral activity of AMD11070 administered in HIV-infected patients who harbor-X4-tropic virus. Time Frame: 10 days	10 days
the proportion of patients per cohort who have a ≥1 log10 rlu reduction in X4-tropic virus and to describe changes from baseline to Day 10 in log10 rlu corresponding to X4-tropic virus. Time Frame: 10 days	10 days

Secondary Outcome Measures

Outcome Measure	Time Frame
the relationship between standard pharmacokinetic (PK) measures, viral response, and a shift in T-cell receptor tropism. Time Frame: 10 days	10 days
the relationship of coreceptor tropism phenotype to CD4+ count, viral load, and drug resistance in the screening patient population. Time Frame: 10 days	10 days
the virologic activity of AMD11070 at day 10 of study treatment by analyzing the proportion of patients with Plasma HIV-1 RNA levels <400 and <50 copies/ml and the proportion with a >1 log10 decline in plasma HIV from baseline. Time Frame: 10 days	10 days
changes in CD4+ cell counts and percentages on and off AMD11070. Time Frame: 10 days	10 days
change from baseline in CD34+ cells Time Frame: 10 days	10 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genzyme, a Sanofi Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Moyle G, DeJesus E, Boffito M, Wong RS, Gibney C, Badel K, MacFarland R, Calandra G, Bridger G, Becker S; X4 Antagonist Concept Trial Study Team. Proof of activity with AMD11070, an orally bioavailable inhibitor of CXCR4-tropic HIV type 1. Clin Infect Dis. 2009 Mar 15;48(6):798-805. doi: 10.1086/597097.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2005

Primary Completion (ACTUAL)

August 1, 2006

Study Completion (ACTUAL)

April 1, 2010

Study Registration Dates

First Submitted

August 3, 2006

First Submitted That Met QC Criteria