A Phase IV Trial of Paritaprevir/Ritonavir, Ombitasvir, Dasabuvir for Chronic Hepatitis C Genotype 1 Virus Infection

NCT02498015 | Completed Phase 4 DMC

• 1 other identifier: VHCRP1405
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

Brief Summary

A total of 100 people with chronic HCV and recent injection drug use or recipients of opioid substitution therapy will be enrolled in 5 countries and 21 study sites. Participants with genotype 1a infection or cirrhosis will receive 12 weeks of open-label paritaprevir/ritonavir/ombitasvir and dasabuvir ("3D"), and twice-daily ribavirin. Participants with genotype 1b infection without cirrhosis will receive 12 weeks of open-label "3D". The study consists of a screening phase (6 weeks), treatment phase (12 weeks) and follow-up phase (96 weeks) to evaluate treatment response and reinfection.

Conditions

Hepatitis C, Chronic

Outcome Measures

Primary Outcomes (1)

• The proportion of participants with undetectable HCV RNA at 12 weeks post end of treatment (SVR12)

  To evaluate the proportion of participants with undetectable HCV RNA 12 weeks post end of treatment (SVR12) following the "3D" regimen with or without ribavirin for 12 weeks in people with chronic HCV genotype 1 infection.

  12 weeks post treatment

Secondary Outcomes (15)

• The proportion of participants with undetectable HCV RNA at 2 weeks following the initiation of treatment - week 2

  2 weeks following the initiation of treatment

• The proportion of participants with undetectable HCV RNA at 4 weeks following the initiation of treatment - week 4

  4 weeks following the initiation of treatment

• The proportion of participants with undetectable HCV RNA at the end of treatment - week 12

  End of treatment week 12

• The proportion of participants with undetectable HCV RNA at 24 weeks post end of treatment (SVR24)

  24 weeks post treatment

• Treatment adherence

  Baseline to week 12

Study Arms (2)

"3D" regimen

EXPERIMENTAL

The "3D" regimen contain two tablets of co-formulated paritepravir/ritonavir/ombitasvir (75/50/12.5 mg) once daily, and one dasabuvir tablet (250 mg) twice daily for genotype 1b without cirrhosis. Treatment will be 12 weeks.

Drug: "3D" regimen

"3D" regimen with ribavirin

EXPERIMENTAL

The "3D" regimen with ribavirin contain two tablets of co-formulated paritepravir/ritonavir/ombitasvir (75/50/12.5 mg) once daily, one dasabuvir tablet (250 mg) twice daily, and ribavirin (1000 mg regardless of weight) daily in two divided doses for genotype 1a (with/without) and genotype 1b with cirrhosis. Treatment will be for 12 weeks.

Drug: "3D" regimen with ribavirin

Interventions

"3D" regimen DRUG

The "3D" regimen contain paritaprevir/ritonavir/ombitasvir (75/50/12.5mg) once daily, dasabuvir 250mg twice daily for genotype 1b without cirrhosis.

Also known as: Viekira pack

"3D" regimen

"3D" regimen with ribavirin DRUG

The "3D" regimen with ribavirin contain paritaprevir/ritonavir/ombitasvir (75/50/12.5mg) once daily, dasabuvir 250mg twice daily, and ribavirin (1000 mg regardless of weight) daily in two divided doses for genotype 1a and genotype 1b with cirrhosis.

Also known as: Viekira pack with ribavirin

"3D" regimen with ribavirin

Eligibility Criteria

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

You may qualify if:

• Detectable HCV RNA in plasma (\>1,000 IU/ml).
• Evidence of positive HCV antibody \>6 months prior to screening.
• HCV Genotype 1 infection.
• Recent IDU (previous 6 months) or receiving stable OST (stable dose for \>2 weeks).
• Never received treatment for HCV infection.
• Compensated liver disease. Enrolment of patients with cirrhosis (FibroScan \>14.6 kPa or FIB-4 \> 3.25) will be capped to 60% of the total enrolment (maximum 3 per site).
• Participants with FibroScan \> 12KPa or AFP \>50 ng/mL must have abdominal ultrasound or CT scan without evidence of hepatocellular carcinoma within 2 months before screening.
• Negative pregnancy test (for women of childbearing potential) within the 24-hour period before the first dose of study drug.
• All fertile participants must be using effective contraception during treatment and 24 weeks post treatment (patients treated with ribavirin) or 2 weeks post treatment (patients not treated with ribavirin).

You may not qualify if:

• Any systemic anti-viral, anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) ≤6 months before the first dose of study drug.
• Any investigational drug ≤6 weeks before the first dose of study drug.
• HIV infection.
• History or other evidence of decompensated liver disease.
• Neutrophil \<1000 cells/mm3 or platelet \<50,000 cells/mm3 at screening.
• Serum creatinine \>1.5 x upper limit of normal at screening.
• Ongoing severe psychiatric disease as judged by the treating physician.
• Frequent IDU that is judged by the treating physician to compromise treatment safety.
• Hemoglobin \<12 g/dL (\<7.4 mmol/L) in women or \<13 g/dL (\<8.1 mmol/L) in men at screening.
• Pregnancy/lactation or male subjects whose female partners are pregnant.
• Subject has current or past clinical evidence of decompensated liver disease, such as ascites, hepatic encephalopathy, oesophageal varices, and/or any of the following screening laboratory results;
• a. International normalised ration (INR) \>1.5; i. Patients with a known inherited blood disorder and INR \> 1.5 may be enrolled after discussion with the Principal Investigator b. Serum albumin \<3.3 g/dL; c. Serum total bilirubin \>1.8 x ULN, unless isolated in subjects with Gilbert's syndrome.
• Subject shows evidence of significant liver disease in addition to HCV, which may include but is not limited to drug- or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, non-alcoholic steatohepatitis (NASH), or primary biliary cirrhosis.
• Subject has active malignant disease or history of malignant disease within the past 5 years (except treated basal cell carcinoma).
• History of chronic pulmonary disease associated with functional limitation, severe cardiac disease, major organ transplantation or other evidence of severe illness, malignancy, or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study.

Sponsors & Collaborators

• Kirby Institute: lead

Study Sites (1)

The Kirby Institute, University of New South Wales Australia

Sydney, New South Wales, 2052, Australia

Location

Related Publications (2)

• Cunningham EB, Hajarizadeh B, Amin J, Hellard M, Bruneau J, Feld JJ, Cooper C, Powis J, Litwin AH, Marks P, Dalgard O, Conway B, Moriggia A, Stedman C, Read P, Bruggmann P, Lacombe K, Dunlop A, Applegate TL, Matthews GV, Fraser C, Dore GJ, Grebely J. Reinfection Following Successful Direct-acting Antiviral Therapy for Hepatitis C Virus Infection Among People Who Inject Drugs. Clin Infect Dis. 2021 Apr 26;72(8):1392-1400. doi: 10.1093/cid/ciaa253.

  PMID: 32166305 DERIVED

• Artenie AA, Cunningham EB, Dore GJ, Conway B, Dalgard O, Powis J, Bruggmann P, Hellard M, Cooper C, Read P, Feld JJ, Hajarizadeh B, Amin J, Lacombe K, Stedman C, Litwin AH, Marks P, Matthews GV, Quiene S, Erratt A, Bruneau J, Grebely J. Patterns of Drug and Alcohol Use and Injection Equipment Sharing Among People With Recent Injecting Drug Use or Receiving Opioid Agonist Treatment During and Following Hepatitis C Virus Treatment With Direct-acting Antiviral Therapies: An International Study. Clin Infect Dis. 2020 May 23;70(11):2369-2376. doi: 10.1093/cid/ciz633.

  PMID: 31300820 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

Ribavirin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Gregory Dore, MBBS, PhD

  Kirby Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 26, 2015
• First Posted: July 15, 2015
• Study Start: August 1, 2016
• Primary Completion: August 1, 2017
• Study Completion: March 1, 2019
• Last Updated: June 13, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)