Immunologic Effects of HCV Therapy With HARVONI in HCV Genotype 1 Chronically Mono-infected Active and Former IDUs

NCT02347345 | Completed Phase 4 Results

• 2 other identifiers: MMA-08745R01DA033777
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The investigator's hypothesis is that active injectors will show a partial reduction in markers of immune activation with HCV therapy whereas non-injectors will show a more significant reduction in these markers, and will exhibit levels of immune activation that approach that seen in similarly studied healthy volunteers.This is based on observations that this group of investigators have made. They have shown that individuals who inject drugs have high level of immune activation in blood and tissue. Immune activation or chronic inflammation has been associated with accelerated aging, cardiovascular, renal and liver disease as well as CNS dysfunction. It remains unclear whether increased levels of immune activation are due to non-sterile injection of drugs, chronic infection with Hepatitis C, chronic opiate use, or perhaps combinations of all 3. To understand the potential contribution of infection with Hepatitis C the investigators will compare levels of immune activation pre- and post treatment with an all oral, one pill once daily, interferon sparing treatment of HCV in 2 groups of chronically HCV infected patients- one actively injecting with drugs and the other free of injection for at least 4 months. Immune activation comparisons will also include non-injecting healthy volunteers.

Conditions

Hepatitis C

Keywords

HCV, injection drug use

Outcome Measures

Primary Outcomes (1)

• sCD14 (ng/mL)

  Marker of immune activation as measured by levels of soluble CD14. Note that the levels of sCD14 were only measured at baseline in the Healthy Volunteers group and therefore there are no data for weeks 4, 12, or 24 entered.

  24 weeks

Secondary Outcomes (2)

• Virologic Response to Therapy as Measured by HCV RNA

  24 weeks

• Gene Expression Profiles

  24 weeks

Study Arms (3)

Active injection drug use (IDU)

ACTIVE COMPARATOR

In active IDU, Harvoni (Fixed dose combination ledipasvir/sofosbuvir), one pill orally daily x 12 weeks

Drug: Harvoni (Fixed dose combination ledipasvir/sofosbuvir)

Former injection drug use (former IDU)

ACTIVE COMPARATOR

In former IDU, Harvoni (Fixed dose combination ledipasvir/sofosbuvir), one pill orally daily x 12 weeks

Drug: Harvoni (Fixed dose combination ledipasvir/sofosbuvir)

Healthy volunteers

NO INTERVENTION

HIV, HCV and HBV negative, never injected drugs, no recreational drugs for at least 2 years (does not include marijuana) and negative urine screen for opiates at the screening visit.

Interventions

Harvoni (Fixed dose combination ledipasvir/sofosbuvir) DRUG

Harvoni (Fixed dose combination ledipasvir/sofosbuvir), one pill daily x 12 weeks

Also known as: Fixed dose combination ledipasvir/sofosbuvir

Active injection drug use (IDU); Former injection drug use (former IDU)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Ability to give written informed consent in English
• Age≥18 and ≤55
• HCV antibody positive
• HCV RNA \>1,000 copies/mL plasma
• HCV treatment naive
• HCV genotype 1a or 1b or mixed type 1
• AST, ALT \<10x ULN
• Direct bilirubin \<3.0
• Platelet count \>50,000
• Creatinine clearance \>30mL/min as estimated by Cockroft Gault
• Hemoglobin \>10 if female, \>11 if male
• Albumin \> 2.8
• INR\<2.0
• If Group A: urine dip for opiates + and active injection drug use of heroin defined as injecting at least 3 times per week.
• If Group B then no IDU for at least 4 months and a negative urine for opiates at screening.

You may not qualify if:

• HIV infection
• Chronic infection with Hepatitis B
• Uncompensated cirrhosis
• Required use of:
• Anticonvulsants: carbamazepine, oxycarbazepine, phenobarbital, and phenytoin
• Antimycobacterials: rifabutin, rifampin, rifapentine
• Herbal Supplements: St. John's wort
• HIV Protease Inhibitors: tipranavir-ritonavir
• Antiarrhythmic Drugs: amiodarone (Cordarone, Nexterone, Pacerone)
• Any medical condition that in the opinion of the investigator would interfere with study participation and medical adherence
• Pregnancy/breast feeding

Sponsors & Collaborators

• Rockefeller University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Rockefeller University Hospital

New York, New York, 10021, United States

Location

Related Publications (3)

• Kowdley KV, Gordon SC, Reddy KR, Rossaro L, Bernstein DE, Lawitz E, Shiffman ML, Schiff E, Ghalib R, Ryan M, Rustgi V, Chojkier M, Herring R, Di Bisceglie AM, Pockros PJ, Subramanian GM, An D, Svarovskaia E, Hyland RH, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Pound D, Fried MW; ION-3 Investigators. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014 May 15;370(20):1879-88. doi: 10.1056/NEJMoa1402355. Epub 2014 Apr 10.

  PMID: 24720702 RESULT

• Lawitz E, Poordad FF, Pang PS, Hyland RH, Ding X, Mo H, Symonds WT, McHutchison JG, Membreno FE. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014 Feb 8;383(9916):515-23. doi: 10.1016/S0140-6736(13)62121-2. Epub 2013 Nov 5.

  PMID: 24209977 RESULT

• Gane EJ, Deray G, Liaw YF, Lim SG, Lai CL, Rasenack J, Wang Y, Papatheodoridis G, Di Bisceglie A, Buti M, Samuel D, Uddin A, Bosset S, Trylesinski A. Telbivudine improves renal function in patients with chronic hepatitis B. Gastroenterology. 2014 Jan;146(1):138-146.e5. doi: 10.1053/j.gastro.2013.09.031. Epub 2013 Sep 22.

  PMID: 24067879 RESULT

MeSH Terms

Conditions

Hepatitis C

Interventions

ledipasvir, sofosbuvir drug combination; Sofosbuvir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Results Point of Contact

• Title: Martin Markowitz MD
• Organization: Aaron Diamond AIDS Research Center

mmarkowitz@adarc.org

212-448-5020

Study Officials

• Martin Markowitz, MD

  ADARC/Rockefeller University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Aaron Diamond Professor/Clinical Director

Study Record Dates

• First Submitted: January 15, 2015
• First Posted: January 27, 2015
• Study Start: November 15, 2016
• Primary Completion: November 15, 2016
• Study Completion: November 15, 2016
• Last Updated: August 13, 2019
• Results First Posted: August 13, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)