Clinical trial NCT00503347: Bavituximab Repeat-Dose Trial in Patients Co-Infected With Chronic Hepatitis C Virus and Human Immunodeficiency Virus
Official title: A Phase Ib Open-Label, Escalating Repeat-Dose Trial of Bavituximab (Chimeric Anti-Phosphatidylserine Monoclonal Antibody) in Patients Co-Infected With Chronic Hepatitis C Virus and Human Immunodeficiency Virus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C Virus
Hiv Infections
Keywords: coinfection with chronic hepatitis C virus and HIV
Treatment Naive
Lead sponsor: Peregrine Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2007-07-18
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial is designed to assess the safety, tolerability, pharmacokinetics and viral kinetics after multiple infusions of bavituximab in patients co-infected with HCV and HIV.

Detailed description: OBJECTIVES:

* To determine the safety and tolerability of bavituximab administered as multiple intravenous (IV) infusions to patients co-infected with HCV and HIV
* To characterize the pharmacokinetic profile and viral kinetics after multiple intravenous infusions of bavituximab to patients infected with HCV and HIV
* To define the maximum tolerated dose (MTD) and/or maximum effective dose (MED) of bavituximab administered as multiple infusions to patients infected with chronic HCV infection and HIV

Eligibility criteria: Inclusion Criteria:

* Written informed consent has been obtained
* Adults 18 years of age or older
* HIV infection documented by detectable HIV RNA PCR
* Absolute CD4+ \> 300 cells/mm3
* Chronic hepatitis C infection based on history and detectable serum HCV RNA
* Serum alanine aminotransferase (ALT) above normal limits and/or historical biopsy consistent with hepatitis C
* Complete blood counts within normal limits
* Normal renal function (serum creatinine within normal limits)
* PT/INR and aPTT within normal limits
* All patients of reproductive potential must agree to use an approved form of barrier contraception or agree not to become pregnant while taking study medications and for 30 days after study completion. Female patients must have a negative serum pregnancy test at prestudy (not applicable to patients with bilateral oophorectomy and/or hysterectomy or to those patients who are postmenopausal)

Exclusion Criteria:

* HCV or HIV antiviral therapy within 4 weeks of Day 0
* Prior exposure to any chimeric antibody
* Any other cause of liver disease other than chronic hepatitis C, such as autoimmune or alcoholic liver disease.
* Decompensated clinical liver disease, including a history of prolonged clotting times, hypoalbuminemia, encephalopathy, treatment for elevated ammonia levels, or ascites
* Any evidence of clinically significant bleeding defined as gross hematuria, hemoptysis, or gastrointestinal bleeding
* Known history of bleeding diathesis or coagulopathy (e.g., von Willebrand Disease or Hemophilia)
* Any history of thromboembolic events \[e.g., deep vein thrombosis (DVT) or pulmonary thromboembolism (PE)\]. A history of including central venous catheter-related thrombosis is acceptable if there is documentation of resolution at least 12 months prior to enrollment.
* Concurrent therapy with oral or parenteral anticoagulants
* Concurrent hormone therapy (i.e., estrogen contraceptives, hormone replacement, anti-estrogen)
* Investigational therapy within 4 weeks of Day 0
* Major surgery within 4 weeks of Day 0
* Pregnant or nursing women
* Uncontrolled intercurrent disease (e.g., diabetes, hypertension, thyroid disease)
* Any history of angina pectoris, coronary artery disease or cerebrovascular accident, or transient ischemic attack
* A history of any condition requiring anti-platelet therapy with the exception of general cardiovascular prophylaxis with aspirin
* A history of any condition requiring treatment (past or current) with coumarin-type agents
* Cardiac arrhythmia requiring medical therapy
* Serious non-healing wound (including wound healing by secondary intention, ulcer, or bone fracture)
* Requirement for chronic daily treatment with NSAIDs, antiplatelet drugs (e.g., phosphodiesterase inhibitors, adenosine diphosphate receptor antagonists), or steroids
* Cancer, autoimmune disease or any disease or concurrent therapy known to cause significant alteration in immunologic function. Corticosteroids administered as pre-treatment, or to treat an adverse event, are allowed.

Primary outcomes:
measure: • Adverse events • Laboratory evaluations • Human anti-chimeric antibody • Pharmacokinetic analysis
Secondary outcomes:
measure: Blood levels of HCV RNA and HIV RNA (PCR)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Impact Clinical Research
state: California
city: Newport Beach
country: United States
facility: Orange Coast Medical Center
state: California
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins University, Center for Viral Hepatitis
state: Maryland
city: Newark
country: United States
facility: Saint Michael's Medical Center
state: New Jersey
city: Dallas
country: United States
facility: Southwest Infectious Disease Associates
state: Texas
Study officials:
affiliation: Saint Michael's Medical Center
name: Jihad Slim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University, Center for Viral Hepatitis
name: Mark S. Sulkowski, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Orange Coast Medical Center
name: Jorge Rodriguez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Southwest Infectious Disease Associates
name: Nicholaos C. Bellos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Impact Clinical Trials
name: Lydie Hazan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: AIDS Research Consortium of Atlanta (ARCA)
name: Melaine Thompson, MD
role: PRINCIPAL_INVESTIGATOR
References: