Impact of Hepatitis C Virus Therapy on Central Nervous System Outcomes

• Status: Recruiting
• Trial end date: 0000-00-00
• Target enrollment: 72
• Participant gender: Both

Summary

This partially blinded placebo-controlled trial will determine the impact of curing Hepatitis C Virus (HCV) with an oral direct-acting antiviral (DAA), ledipasvir and sofosbuvir in a single pill, on central nervous system (CNS) outcomes in mono- or Human Immunodeficiency Virus (HIV) co-infected individuals.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Diego
• Collaborator: Gilead Sciences
• Treatments: Ledipasvir; Ledipasvir, sofosbuvir drug combination; Sofosbuvir
• Last Updated: 2016-04-11

Criteria

Inclusion Criteria:

1. Adult (≥ 18 years old) subjects with chronic genotype 1 HCV and NCI with a GDS greater than or equal to 0.5 (n=60).

2. Presence of chronic HCV infection based on chart review will be defined as positive for anti-HCV antibody or HCV RNA at least 6 months before screening.

3. For the HIV/HCV co-infected group only, subjects must have HIV. HIV status will be obtained through self report. Self report will be confirmed at screening using a HIV-1 point of care test. In the event that point of care test and self-report are discordant, then HIV status will be confirmed by a licensed Western blot or a second antibody test.

4. HIV/HCV co-infected subjects (n=12) must also have a HIV RNA measurement <50 copies/mL at the pre-treatment visit.

5. Laboratory values:

• Platelets >150,000

• Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) <10x upper limit of normal

• Creatinine clearance >30 milliliters/minute/1.73 centimeter squared

Exclusion Criteria:

1. Ledipasvir (LDV)/Sofosbuvir (SOF) is known to have drug interactions if co-administered with the following drugs:

• Amiodarone

• P-glycoprotein (P-gp) inducers (e.g., rifampin, St. John's wort)

2. Cirrhosis or bridging fibrosis (Modified hepatic activity index (mHAI) stages 4-6 or its equivalent).

• Liver biopsy at any time showing mHAI stage 4 or higher fibrosis OR

• FibroScan within 12 months demonstrating liver stiffness of ≥9.5 kilo Pascal or

• AST to platelet ratio index (APRI) ≥2.0 and Fibrosis-4 (FIB-4) ≥3.25

• NOTE: If APRI and FIB-4 are discordant one of the other forms of fibrosis staging must be used.

3. Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.

4. Any cause of liver disease other than chronic HCV infection, including but not limited to the following:

• Hemochromatosis

• Alpha-1 antitrypsin deficiency

• Wilson's disease

• Autoimmune hepatitis

• Alcoholic liver disease

• Drug-related liver disease

5. Severe NC confounding conditions (stroke, head injury, or developmental learning disability).

6. Regular use of anti-inflammatory drugs.

7. Current or recent treatment with pegylated interferon (PEG-IFN).

8. Other active inflammatory process (major infection, malignancy, rheumatoid arthritis/autoimmune disorder) within the prior 28 days.

9. Contraindications to magnetic resonance imaging (MRI).

10. Bleeding diathesis, thrombocytopenia, or use of anticoagulants that would contraindicate lumbar puncture.

11. Uncontrolled or active depression or other psychiatric disorder that in the opinion of the site investigator might preclude adherence to study requirements or impact NC functioning and assessments.

12. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.

13. Presence of active or acute AIDS-defining opportunistic infections within 12 weeks prior to study entry.