Impact of Hepatitis C Therapy and Bone Health

NCT ID: NCT03221582

Last Updated: 2019-08-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-28
• Study Completion Date: 2018-11-30

Brief Summary

An evaluation of the impact of Elbasvir and Grazoprevir (EBR/GZR) HCV therapy on the heart risk and bone health of HCV mono-infected and HIV/HCV co-infected patients.

Detailed Description

Both HCV and HIV are associated with an increased risk of osteoporosis and osteoporotic fractures among HIV-infected patients and the general population. While HIV significantly increases cardiovascular risk, the contribution of HCV to cardiovascular disease (CVD) is less certain. Increased inflammation could potentially underlie the effect of HCV on CVD, bone health, and other extra-hepatic complications. HCV appears to remain an independent predictor of osteoporotic fractures even after controlling for severity of liver disease. The impact of HCV therapy on inflammation, CVD and bone health is unclear. Our previous studies suggest a beneficial impact of interferon therapy on bone turnover and some CVD markers, while others studies have found on-treatment increases in bone mineral density with interferon-based therapy. Whether these are related to the interferon itself or the virologic response, and whether changes in biomarkers lead to improved fracture risk or CVD morbidity is uncertain. Investigator propose to conduct a prospective analysis of markers of inflammation, immune activation, and bone turnover as well as bone mineral density (BMD) among both HIV/HCV co-infected and HCV mono-infected patients undergoing treatment with the novel direct-acting antiviral elbasvir/grazoprevir (EBR/GZR). Should EBR/GZR therapy significantly improve CV risk and bone health, it would be an additional benefit and indication for its use in HCV therapy.

Conditions

Human Immunodeficiency Virus; Hepatitis C

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

EBR/GZR (Zepatier) - HCV/HIV co-infected

Drug: Elbasvir (EBR) 50 mg and Grazoprevir (GZR) 100 mg single tablet by mouth, once daily.

Group Type: EXPERIMENTAL

EBR/GZR

Intervention Type: DRUG

Elbasvir and Grazoprevir (EBR/GZR) tablet by mouth, once daily.

EBR/GZR (Zepatier) - HCV monoinfected

Drug: Elbasvir (EBR) 50 mg and Grazoprevir (GZR) 100 mg single tablet by mouth, once daily.

Group Type: EXPERIMENTAL

EBR/GZR

Intervention Type: DRUG

Elbasvir and Grazoprevir (EBR/GZR) tablet by mouth, once daily.

Interventions

EBR/GZR

Elbasvir and Grazoprevir (EBR/GZR) tablet by mouth, once daily.

Intervention Type: DRUG

Other Intervention Names

Zepatier

Eligibility Criteria

Inclusion Criteria

1. HCV antibody and HCV RNA positive

2. HCV Genotype 1a, 1b, or 4

3. Liver staging assessment:

a. Cirrhosis will be defined by any of the following: i. A liver biopsy prior to day 1 of this study showing cirrhosis (F4) ii. Fibroscan within 12 calendar months of day 1 of this study showing cirrhosis with result > 12.5 kPa iii. FibroSURE performed during screening with a score > 0.75 and APRI > 2 b. Absence of cirrhosis will be defined by any of the following: i. Liver biopsy performed within 24 months of day 1 of this study showing absence of cirrhosis ii. Fibroscan performed within 12 months of day 1 of this study with a result of ≤ 12.5 kPa iii. FibroSURE score ≤ 0.48 and APRI ≤ 1 during screening

4. If HIV co-infected, HAART regimen will consist of two NRTIs (abacavir, tenofovir disoproxil fumarate or tenofovir alafenamide, each in combination with lamivudine or emtricitabine) with one of the following 3rd agents:

1. raltegravir

2. dolutegravir

3. rilpivirine HIV co-infected patients must be on their stable HAART regimen for at least 6 months, with HIV viral load < 50 c/mL at screening

Exclusion Criteria

1. Hepatitis B surface antigen positivity

2. Decompensated cirrhosis (Child Pugh B or C)

3. Any prior hepatitis C treatment

4. Pregnant or nursing

5. Treatment with any medication specifically contraindicated with EBR/GZR or not recommended for concomitant use as per the prescribing label (Table 2)

6. Age less than 18

7. Prisoners or subjects otherwise involuntarily incarcerated

8. Absence of signed informed consent by patient or appropriate surrogate

9. Known hypersensitivity to elbasvir or grazoprevir

10. For patients with genotype 1a, one more of the following mutations on baseline NS5A genotype: M28, Q30, L31, or Y93

• Minimum Eligible Age: 40 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Dallas VA Medical Center

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roger Bedimo, MD

Role: PRINCIPAL_INVESTIGATOR

Dallas VAMC

Locations

Dallas VA Medical Center

Dallas, Texas, United States

Countries

United States

Other Identifiers

MISP 54850

Identifier Type: -

Identifier Source: org_study_id