Sofosbuvir Based DAA Therapy in HIV/HCV Coinfected Pre or Post Liver Transplant

NCT02533934 | Completed Phase 4 Results

• 2 other identifiers: 120441U01AI115714
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 8

Brief Summary

Retrospective/Prospective, open-label study using sofosbuvir based DAA therapy to treat HIV/HCV coinfected pre or post liver transplant participants

Conditions

HIV; Hepatitis C; Cirrhosis

Keywords

HIV; Hepatitis C; Liver Disease; HCV Treatment; transplant

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Sustained Virologic Response (SVR)

  Sustained virologic response (SVR) defined by hepatitis C virus (HCV) RNA less than the lower level limit of quantification (LLOQ) of \<15 IU/ml at a median time of 38.5 months after the end of sofosbuvir-based direct-acting antiviral (DAA) therapy

  Median time from end of treatment was 38.5 months

Secondary Outcomes (4)

• Reversal in Decompensation

  Median months from baseline to last MELD measurement is 48 months

• Change in Liver Fibrosis

  Median months from baseline to last APRI measurement is 41 months Median months from baseline to last FIB-4 measurement is 41 months

• HIV Viral Breakthrough or Relapse

  Median months from baseline to last HIV follow-up is 38 months

• Number of Subjects Treated With Sofosbuvir-based DAA Therapy Who Had Alanine Aminotransferase (ALT) Normalization Post Treatment (Normal Reference Range: 7 - 55 IU/L)

  Median months from baseline to last ALT measurement is 41 months

Study Arms (1)

Treatment with Sofosbuvir based HCV Therapy

EXPERIMENTAL

Prospective and retrospective treatment for HCV

Drug: Harvoni

Interventions

Harvoni DRUG

Treatment of Hepatitis C with sofosbuvir based HCC therapy

Also known as: SOF/LDV

Treatment with Sofosbuvir based HCV Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The intent of the Retrospective Arm is to capture all HIV/HCV coinfected patients exposed to sofosbuvir based DAA therapy since 2014, to mirror the population enrolled in the Prospective Arm.
• Liver transplant candidates (listed) and decompensated cirrhotics (not listed) for liver transplant
• Treated with sofosbuvir based DAA for any duration since 2014
• Age \>18 years at time of treatment
• Pre-treatment Child's Pugh score of 7 or greater
• Pre-treatment laboratory MELD \>=6 and \<=0
• Survived at least 12 weeks after start of treatment
• HIV-positive on stable ART for at least 4 weeks pre-treatment
• Chronic HCV infection with at least one measurement of plasma HCV RNA \>= 1,000 IU/mL prior to treatment with sofosbuvir based DAA therapy
• HCV genotype 1, 4, 5 or 6
• Liver transplant recipients
• Treated with sofosbuvir based DAA post liver transplant for any duration since 2014
• Liver transplant from 2000 to current
• Age \>18 years at time of treatment
• Treated initiated at least 1 month post-liver transplant

You may not qualify if:

• Pre-liver transplant candidates
• Enrollment will be targeted to occur at least 12 weeks prior to anticipated transplant date.
• Screening laboratory MELD \>=6 and \<=20 (NIH) or \<=30 (non-NIH sites)
• Post-liver transplant recipients
• Recipients with evidence of recurrent HCV viremia
• Subjects with compensated and decompensated liver disease
• Screening laboratory MELD \>=6 and \<=20 (NIH) or \<=30 (non-NIH sites)
• Life expectation of \>12 weeks
• Over 18 years of age at screening
• Female participants of child bearing potential must have a negative urine pregnancy test at day 0 prior to dosing.
• Has received a liver transplant for HCV or has decompensated cirrhosis (Child's Pugh score of 7 or greater)
• Have HIV-1 infection and either:
• On HIV medications (antiretrovirals) for at least 4 weeks WITH
• An HIV viral load less than the level of detection OR
• On no HIV medications for at least 8 weeks WITH:

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Icahn School of Medicine at Mount Sinai: collaborator
• Columbia University: collaborator
• University of Pennsylvania: collaborator
• University of Maryland, College Park: collaborator
• Georgetown University: collaborator
• Johns Hopkins University: collaborator
• National Institutes of Health Clinical Center (CC): collaborator

Study Sites (8)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20057, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Medical Center

Baltimore, Maryland, 21287, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Mt. Sinai Medical Center

New York, New York, 10029, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Hepatitis C; Fibrosis; Liver Diseases

Interventions

ledipasvir, sofosbuvir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

This study was limited by the necessity to change the design from a prospective to a retrospective/prospective analysis. This change in study design resulted from the urgency in treating the HIV/HCV coinfected liver transplant candidate with DAAs, based on the dismal survival outcome in this cohort. By the time this trial was approved, many of the DAAs for HCV were approved, and centers immediately treated their decompensated HIV/HCV recipients.

Results Point of Contact

• Title: Rodney Rogers
• Organization: University of California San Francisco

Rodney.Rogers@ucsf.edu

+14155951226

Study Officials

• Peter Stock, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Henry Masur, MD

  National Institutes of Health Clinical Center (CC)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2015
• First Posted: August 27, 2015
• Study Start: August 1, 2016
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: February 2, 2021
• Results First Posted: February 2, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)