Pilot Trial of Bavituximab Combined With Ribavirin for Initial Treatment of Chronic HepC Virus Genotype 1 Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Peregrine Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01273948
First received: January 7, 2011
Last updated: February 2, 2012
Last verified: February 2012
  Purpose

This will be a randomized, open-label, active-control Phase II pilot trial of bavituximab combined with ribavirin for initial treatment of chronic HCV genotype 1 infection. Eligible patients with normal coagulation, hematological, and renal function will undergo a screening/washout period of up to 28 days, followed by randomization to receive weekly bavituximab or PEG-IFN alpha-2a therapy for 12 weeks, both with twice-daily ribavirin.

The primary endpoint of this study is the proportion of patients who show a greater than or equal to 2-log10 IU reduction in plasma HCV RNA level after 12 weeks of treatment (early virological response; EVR).

Secondary endpoints include the proportion of patients with an undetectable HCV RNA level after 12 weeks of treatment; the proportion of patients who show a reduction in HCV RNA level of greater than or equal to 2 log10 IU after 4 weeks of treatment, viral kinetics for individual patients over time, and comprehensive evaluation of the safety and tolerability of bavituximab infusion.


Condition Intervention Phase
Hepatitis C
Drug: Bavituximab
Drug: Pegylated interferon (PEG-IFN)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Active-Control Phase II Pilot Trial of Bavituximab Combined With Ribavirin for Initial Treatment of Chronic Hepatitis C Virus Genotype 1 Infection

Resource links provided by NLM:


Further study details as provided by Peregrine Pharmaceuticals:

Primary Outcome Measures:
  • Reduction in Hepatitis C Virus RNA [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    The primary endpoint is the proportion of patients who show a greater or equal 2-log(10) IU reduction in HCV RNA level at Study Week 12 (early virological response, EVR).


Enrollment: 66
Study Start Date: January 2011
Study Completion Date: February 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bavituximab 3 mg/kg
Bavituximab 3 mg/kg given by intravenous (IV) infusion once weekly, plus oral ribavirin 1000 mg (weight <75 kg) or 1200 mg (weight greater than or equal to 75 kg) divided into twice-daily doses, for 12 weeks
Drug: Bavituximab
  1. Bavituximab 3 mg/kg given by intravenous (IV) infusion once weekly, plus oral ribavirin 1000 mg (weight <75 kg) or 1200 mg (weight greater than or equal to 75 kg) divided into twice-daily doses, for 12 weeks or
  2. Bavituximab 0.3 mg/kg given by IV infusion once weekly, plus oral ribavirin 1000 mg (weight <75 kg) or 1200 mg (weight greater than or equal to 75 kg) divided into twice-daily doses, for 12 weeks or
Other Name: Bavituxmab
Experimental: Bavituximab 0.3 mg/kg
Bavituximab 0.3 mg/kg given by IV infusion once weekly, plus oral ribavirin 1000 mg (weight <75 kg) or 1200 mg (weight greater than or equal to 75 kg) divided into twice-daily doses, for 12 weeks
Drug: Bavituximab
  1. Bavituximab 3 mg/kg given by intravenous (IV) infusion once weekly, plus oral ribavirin 1000 mg (weight <75 kg) or 1200 mg (weight greater than or equal to 75 kg) divided into twice-daily doses, for 12 weeks or
  2. Bavituximab 0.3 mg/kg given by IV infusion once weekly, plus oral ribavirin 1000 mg (weight <75 kg) or 1200 mg (weight greater than or equal to 75 kg) divided into twice-daily doses, for 12 weeks or
Other Name: Bavituxmab
Active Comparator: Pegylated interferon (PEG-IFN)
Pegylated interferon (PEG-IFN) alpha-2a 180 micrograms given by subcutaneous (SC) injection once weekly, plus oral ribavirin 1000 mg (weight <75 kg) or 1200 mg (weight greater than or equal to 75 kg) divided into twice-daily doses, for 12 weeks
Drug: Pegylated interferon (PEG-IFN)
Pegylated interferon (PEG-IFN) alpha-2a 180 micrograms given by subcutaneous (SC) injection once weekly, plus oral ribavirin 1000 mg (weight <75 kg) or 1200 mg (weight greater than or equal 75 kg) divided into twice-daily doses, for 12 weeks
Other Name: Pegasys

Detailed Description:

Primary Objective: The primary objective of this study is to assess the effect of 12 weeks of initial treatment with bavituximab versus PEG-IFN, each combined with ribavirin, on plasma HCV RNA level in patients with chronic HCV genotype 1 infection.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female between the ages of 18 and 65 years
  2. Chronic hepatitis C virus (HCV) genotype 1 infection
  3. HCV RNA level >10,000 IU/mL
  4. Chronic HCV infection, defined as:

    • Previous documentation of positive HCV serology (HCV antibody or RNA) at least 6 months (24 weeks) previously, or
    • Positive HCV serology (HCV antibody or RNA) with a prior remote (more than 6 months previously) risk factor for acquisition of HCV or
    • Historical biopsy consistent with chronic HCV infection
  5. No clinically significant abnormalities in hematology, coagulation, or chemistry variables:

    • Hemoglobin >12 g/dL for women; >13 g/dL for men
    • Total white cell count >3000/mm3 and absolute neutrophil count >1500/mm3
    • Platelets >100,000/mm3
    • Prothrombin time (PT) and/or international normalized ratio (INR) less than or equal to 1.2 times the local upper limit of normal (ULN)
    • Conjugated (direct) bilirubin less than or equal to 1.5 times the ULN
    • Serum creatinine within normal limits
    • Thyroid-stimulating hormone (TSH) and free thyroxine (T4) within normal limits
  6. Female patients: negative urine pregnancy test
  7. Ability to provide informed consent

Exclusion Criteria:

  1. Previous interferon-based antiviral therapy for chronic HCV infection
  2. Previous treatment with known immunogenic drugs
  3. Concomitant human immunodeficiency (HIV) or hepatitis B virus (HBV) infection
  4. Cause of liver disease other than chronic HCV infection, such as autoimmune or alcoholic liver disease
  5. Decompensated clinical liver disease, including a history of encephalopathy, bleeding esophageal or gastric varices, or ascites
  6. Recipient of liver or other solid-organ transplantation
  7. Evidence of clinically significant bleeding, defined as gross hematuria, hemoptysis, or gastrointestinal bleeding
  8. History of bleeding diathesis or coagulopathy (eg, von Willebrand disease or hemophilia)
  9. History of thromboembolic events (eg, deep-vein thrombosis [DVT] or pulmonary embolism). Previous central venous catheter-related thrombosis is acceptable if there is resolution recorded at least 12 months before enrollment.
  10. Requirement for concurrent treatment with oral or parenteral anticoagulants or hormones (estrogen-containing contraceptives, hormone replacement, antiestrogen agents, progestins)
  11. Condition requiring daily therapy with antiplatelet agents (eg, thienopyridines, dipyridamole, cilostazol; cardiovascular prophylaxis with aspirin is allowed) or corticosteroids
  12. Investigational therapy within 28 days before the first planned dose of study drug
  13. Major surgery within 28 days before the first planned dose of study drug
  14. Uncontrolled intercurrent disease (eg, diabetes, hypertension, thyroid disease)
  15. Ongoing angina pectoris or other symptoms of coronary artery disease (CAD); history of stroke, or transient ischemic attack (TIA)
  16. History of suicidal ideation or attempt
  17. Condition requiring treatment (past or current) with coumarin-type agents
  18. Cardiac arrhythmia requiring medical therapy
  19. Serious nonhealing wound (including wound healing by secondary intention, ulcer, or bone fracture)
  20. Cancer, autoimmune disease, or any disease or concurrent therapy known to cause significant alteration in immune function (corticosteroids are allowed before study enrollment and during the study to treat an AE)
  21. Female patients and female partners of male patients: pregnancy, lactation, or inability/unwillingness to practice effective contraception
  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: NCT01273948

Locations
Georgia
LTD Vakhtang Bochorishvili Anticeptic Centre
Tbilisi, Georgia
Sponsors and Collaborators
Peregrine Pharmaceuticals
Investigators
Study Chair: Janet Nuttall, MPH Peregrine Pharmaceuticals
  More Information

No publications provided

Responsible Party: Peregrine Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01273948     History of Changes
Other Study ID Numbers: PPHM 1003
Study First Received: January 7, 2011
Last Updated: February 2, 2012
Health Authority: United States: Food and Drug Administration
Georgia: Ministry of Health
Russia: Ministry of Health of the Russian Federation

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Antibodies, Monoclonal
Interferons
Ribavirin
Anti-Infective Agents
Antimetabolites
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014