Ribavirin Loading Dose or Priming and Concentration Targeting for HCV Genotype 1

NCT01226771 | Completed Phase 3 DMC

• 2 other identifiers: Eu-nr 2010-018332-412010-018332-41
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, open-label, parallel group, multicenter pilot study evaluating the efficacy and safety of alternative dosing of ribavirin vs. standard of care dosing in combination with peginterferon alpha-2a in interferon naïve patients with chronic hepatitis c genotype 1 infection.

Conditions

Hepatitis C

Keywords

hepatitis V virus; genotype 1; ribavirin; interferon; Alternative ribavirin dosing

Outcome Measures

Primary Outcomes (1)

• The early virological response as measured by decline in HCV-RNA during the first 12 weeks of peginterferon alpha-2a and ribavirin therapy in the three study arms.

  The first 12 weeks of therapy

Secondary Outcomes (1)

• VRVR, RVR, cEVR, pEVR, SVR, and Relapse rates

  Throughout the treatment period including 24 weeks post completion of therapy

Study Arms (3)

Group A ("Loading")

EXPERIMENTAL

PEG-IFN α-2a 180 μg/week plus loading (≥26 mg/kg/day for 2 weeks followed by ≥13 mg/kg/day) and concentration targeted (≥ 2.5 mg/L, i.e ≥ 10.25 μmol/L, as measured after 4 weeks of therapy) dosing of ribavirin and response guided treatment duration (RVR 24 weeks, non-RVR 48 weeks, pEVR consider 72 weeks), follow-up period 24 weeks

Drug: Ribavirin "loading" dose given

Group B ("Priming")

EXPERIMENTAL

Standard-of-care dosing of ribavirin (≥13 mg/kg/day) without PEG-IFN for 4 weeks followed by 24-48 additional weeks of PEG-IFN α-2a 180 μg/week plus standard-of-care dosing of ribavirin (≥13 mg/kg/day) and concentration targeted (≥ 2.5 mg/L, i.e ≥ 10.25 μmol/L, as measured after 28 days after the initiation of ribavirin) dosing of ribavirin and response guided treatment duration (RVR 28 weeks, non-RVR 52 weeks, pEVR consider 76 weeks), follow-up period 24 weeks

Drug: "Priming" dose of ribavirin given

Group C ("Standard-of-Care)

ACTIVE COMPARATOR

PEG-IFN α-2a 180 μg/week plus standard-of-care dosing of ribavirin (≥13 mg/kg/day without any measurement of ribavirin concentration) and response guided treatment duration (RVR 24 weeks, non-RVR 48 weeks, pEVR consider 72 weeks), follow-up period 24 weeks

Drug: Group C ("Standard-of-Care")

Interventions

Ribavirin "loading" dose given DRUG

PEG-IFN α-2a 180 μg/week plus loading (≥26 mg/kg/day for 2 weeks followed by ≥13 mg/kg/day) and concentration targeted (≥ 2.5 mg/L, i.e ≥ 10.25 μmol/L, as measured after 4 weeks of therapy) dosing of ribavirin and response guided treatment duration (RVR 24 weeks, non-RVR 48 weeks, pEVR consider 72 weeks), follow-up period 24 weeks

Group A ("Loading")

"Priming" dose of ribavirin given DRUG

Standard-of-care dosing of ribavirin (≥13 mg/kg/day) without PEG-IFN for 4 weeks followed by 24-48 additional weeks of PEG-IFN α-2a 180 μg/week plus standard-of-care dosing of ribavirin (≥13 mg/kg/day) and concentration targeted (≥ 2.5 mg/L, i.e ≥ 10.25 μmol/L, as measured after 28 days after the initiation of ribavirin) dosing of ribavirin and response guided treatment duration (RVR 28 weeks, non-RVR 52 weeks, pEVR consider 76 weeks), follow-up period 24 weeks

Group B ("Priming")

Group C ("Standard-of-Care") DRUG

PEG-IFN α-2a 180 μg/week plus standard-of-care dosing of ribavirin (≥13 mg/kg/day without any measurement of ribavirin concentration) and response guided treatment duration (RVR 24 weeks, non-RVR 48 weeks, pEVR consider 72 weeks), follow-up period 24 weeks

Group C ("Standard-of-Care)

Eligibility Criteria

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

You may qualify if:

• Written informed consent
• Male and female patients ≥18 years of age
• Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test
• Serum HCV-RNA ≥15 IU/mL.
• HCV genotype 1 infection confirmed within the past 2 years preceding the initiation of test drug dosing.
• Compensated liver disease (Child-Pugh Grade A clinical classification)
• Patients with cirrhosis or transition to cirrhosis must have an abdominal ultrasound, CT scan, or MRI scan without evidence of hepatocellular carcinoma and a serum AFP ≤100 ng/mL within 2 months of randomization
• Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug
• All fertile males and females receiving ribavirin must be using effective contraception during treatment and during 4 months for female patients / 7 months for male patients after end of treatment
• Subject must weigh between 45 and 105 kg at screening

You may not qualify if:

• Women with ongoing pregnancy or breast feeding
• IFN/ peg-interferon with or without ribavirin therapy at any previous time
• Therapy with any systemic anti-viral, anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) \*6 months prior to the first dose of study drug
• Any investigational drug ≤6 weeks prior to the first dose of study drug.
• HCV genotype 2, 3, 4, 5, 6, or 7 infection.
• Positive test at screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, anti-HIV Ab
• Evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures)
• History or other evidence of decompensated liver disease
• Neutrophil count \<1500 cells/mm3 or platelet count \<90,000 cells/mm3 at screening
• Serum creatinine level \>2 mg/dl (\>124 µmol/L) or creatinine clearance ≤50 ml/minute at screening
• Severe psychiatric disease, especially depression, as judged by the treating physician.
• History of a severe seizure disorder or current anticonvulsant use
• History of immunologically mediated disease, severe 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
• Thyroid dysfunction not adequately controlled (TSH and T4 levels out of normal range)
• Evidence of severe retinopathy (e.g. CMV retinitis, macula degeneration) or clinically relevant ophthalmological disorder due to diabetes mellitus or hypertension

Sponsors & Collaborators

• Göteborg University: lead
• The Swedish Research Council: collaborator
• Roche Pharma AG: collaborator

Study Sites (1)

Dept. of Infectious Diseases

Gothenburg, Sweden

Location

Related Publications (1)

• Waldenstrom J, Westin J, Nystrom K, Christensen P, Dalgard O, Farkkila M, Lindahl K, Nilsson S, Norkrans G, Krarup H, Norrgren H, Rauning Buhl M, Stenmark S, Lagging M. Randomized Trial Evaluating the Impact of Ribavirin Mono-Therapy and Double Dosing on Viral Kinetics, Ribavirin Pharmacokinetics and Anemia in Hepatitis C Virus Genotype 1 Infection. PLoS One. 2016 May 11;11(5):e0155142. doi: 10.1371/journal.pone.0155142. eCollection 2016.

  PMID: 27167219 DERIVED

MeSH Terms

Conditions

Hepatitis C

Interventions

Standard of Care

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)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2010
• First Posted: October 22, 2010
• Study Start: September 1, 2010
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: March 24, 2015

Record last verified: 2015-03

Locations

SE (1)