Trial of Simplified Treatment Monitoring for 8 Weeks Glecaprevir/Pibrentasvir in Chronic Hepatitis C Patients

NCT ID: NCT03117569

Last Updated: 2019-12-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 380 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-21
• Study Completion Date: 2018-12-19

Brief Summary

The aim of this study is to determine if treatment monitoring schedule for chronic HCV patients treated with glecaprevir (300mg)/pibrentasvir (120mg) can be simplified.

Data has shown that direct acting antiviral (DAA) regimen of glecaprevir (300mg)/pibrentasvir (120mg), a protease inhibitor and NS5A inhibitor respectively , provides key features for HCV treatment simplification.

Eligible participants (naïve pre-cirrhosis chronic HCV patients) will be randomized (1:2) to the standard or simplified monitoring arm and will receive treatment for 8 weeks.

One post treatment visit will be conducted 12 weeks after the final dose of study medication to evaluate the proportion of patients with undetectable HCV RNA at this timepoint (SVR12).

Detailed Description

The capacity to scale-up interferon-free DAA therapy would be enhanced by simplified treatment monitoring strategies. The "next generation" DAA regimen of glecaprevir (300mg)/pibrentasvir (120mg), a protease inhibitor and NS5A inhibitor, provides key features for HCV treatment simplification, including on-treatment monitoring: 1) pangenotypic activity with extremely high efficacy (SVR>95%); 2) no relationship between time to undetectable HCV RNA and SVR; 3) minimal drug-related toxicity; 4) ease of dosing (three pills once daily); and short duration (8 weeks in non-cirrhosis and 12 weeks in cirrhosis for treatment naïve patients). In phase II and III clinical trials in participants without cirrhosis, 8 weeks of glecaprevir (300mg)/pibrentasvir (120mg) has provided intention-to-treat SVR rates of 99.1%, 98%, 97%, and 93.1% in genotype 1, 2, 3, and 4-6 populations, respectively.

Current standard on-treatment monitoring in clinical trials involves clinic-based visits every 4 weeks. In the DAA era where treatments are highly tolerable, effective and short duration, this intensive monitoring strategy may no longer be required. A simplified on-treatment monitoring strategy is hypothesised to be non-inferior to the standard clinical trial on treatment monitoring strategy. If successful, a simplified on-treatment monitoring strategy is likely to be highly attractive to patients, clinicians and health care payers. It has the potential to improve the rapid scale up of treatment providing population level benefits in the reduction of global hepatitis C disease burden.

This study will be conducted as a Phase IIIb, randomised, controlled, multicentre, international trial.

There will be a maximum screening period of 6 weeks prior to Baseline. Eligible patients will be randomised into one of two on-treatment monitoring strategies; standard clinical trial monitoring (4-weekly on-treatment visits) vs simplified monitoring (no on-treatment visits). Randomisation will be 1:2 (standard vs simplified) and all participants will receive treatment with glecaprevir (300mg)/pibrentasvir (120mg) for 8 weeks.

All participants will attend the clinic for screening and baseline visit. Randomisation will occur at the baseline visit.

The two on-treatment monitoring strategies will differ as follows:

• Standard monitoring arm participants will have on-treatment clinic visits at weeks 4 and 8 (EoT).
• Simplified monitoring arm participants will have no on-treatment clinic visits.

Study nurse phone contact will also be made to participants in BOTH arms 1-2 days prior Week 4 and EoT (Week 8) visits to provide standardized reporting of adverse events, concomitant medication and adherence. One post treatment clinic visit will be conducted at SVR12 (week 20) for all participants.

Conditions

Hepatitis C, Chronic

Study Design

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

Study Groups

Standard monitoring schedule

Participants will have on-treatment clinic visits at weeks 4 and 8. Participants have also phone contact-based visits at weeks 4 and 8 (1-2 days prior to scheduled clinic visits).

Group Type: OTHER

glecaprevir (300mg)/pibrentasvir (120mg)

Intervention Type: DRUG

glecaprevir (300mg)/pibrentasvir (120mg) for 8 weeks

Simplified monitoring schedule

Participants will have no on-treatment clinic visits at weeks 4 and 8. Participants have phone contact-based visits at weeks 4 and 8.

Group Type: EXPERIMENTAL

glecaprevir (300mg)/pibrentasvir (120mg)

Intervention Type: DRUG

glecaprevir (300mg)/pibrentasvir (120mg) for 8 weeks

Interventions

glecaprevir (300mg)/pibrentasvir (120mg)

glecaprevir (300mg)/pibrentasvir (120mg) for 8 weeks

Intervention Type: DRUG

Other Intervention Names

Mavyret

Eligibility Criteria

Inclusion Criteria

1. Have voluntarily signed the informed consent form.

2. 18 years of age or older.

3. Chronic HCV infection as defined by anti-HCV antibody or HCV RNA detection for greater than 6 months.

4. HCV RNA plasma ≥ 10,000 IU/ml at screening.

5. HCV genotype 1-6.

6. HCV treatment naïve (no prior treatment with an approved or investigation anti-HCV medication).

7. Stage F0-3, based on: hepatic elastography <12.5 kPa on Fibroscan® or APRI <1.0.

8. If co-infection with HIV is documented, the subject must meet the following criteria:

• ART naïve with CD4 T cell count >500 cells/mm3; OR
• On a stable ART regimen (containing only permissible ART - see protocol section 3.2) for >8 weeks prior to screening visit, with CD4 T cell count >200 cells/mm3 and a plasma HIV RNA level below the limit of detection.

9. Negative pregnancy test at screening and baseline (females of childbearing potential only).

10. All fertile females must be using effective contraception during treatment and during the 30 days after treatment end.

Exclusion Criteria

1. History of any of the following:

1. Clinically significant illness (other than HCV) or any other major medical disorder that may interfere with the participant treatment, assessment or compliance with the protocol; participants currently under evaluation for a potentially clinically significant illness (other than HCV) are also excluded.

2. Clinical hepatic decompensation (i.e. ascites, encephalopathy or variceal haemorrhage).

3. Solid organ transplant.

4. History of severe, life-threatening or other significant sensitivity to any excipients of the study drugs.

2. Any of the following lab parameters at screening:

1. ALT > 10 x ULN

2. AST > 10 x ULN

3. Direct bilirubin > ULN

4. Platelets < 90,000/μL (cells/mm3) if Fibroscan® <12.5 kPa OR < 150,000/μL (cells/mm3) if Fibroscan® is unavailable and patient is included with APRI <1

5. Creatinine clearance (CLcr) < 50 mL/min

6. Haemoglobin < 12g/dL for males; <11g/dL for females

7. Albumin < LLN

8. INR > 1.5 ULN unless subject has known haemophilia or is stable on an anticoagulant regimen affecting INR

3. Pregnant or breastfeeding female.

4. HBV infection (HBsAg positive).

5. Use of prohibited concomitant medications as described in protocol section 5.2.

6. Chronic use of systemically administered immunosuppressive agents (e.g. prednisone equivalent > 10 mg/day for >2 weeks).

7. Therapy with any anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) ≤6 months prior to the first dose of study drug.

8. Any investigational drug ≤6 weeks prior to the first dose of study drug.

9. Ongoing severe psychiatric disease as judged by the treating physician.

10. Positive result of a urine drug screen at the Screening Visit for opiates, barbiturates, amphetamines, cocaine, benzodiazepines, phencyclidine, propoxyphene, or alcohol, with the exception of a positive result (including methadone) associated with documented short-term use or chronic stable use of a prescribed medication in that class.

11. Injecting drug use within the previous six months.

12. Inability or unwillingness to provide informed consent or abide by the requirements of the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kirby Institute

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gregory Dore

Role: PRINCIPAL_INVESTIGATOR

Kirby Institute, University of New South Wales Sydney, Australia

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

New York University Langone Medical Center

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

SSM Health Dean Medical Group

Madison, Wisconsin, United States

East Sydney Doctors

Sydney, New South Wales, Australia

St Vincent's Hospital Sydney

Sydney, New South Wales, Australia

Holdsworth House Medical Practice

Sydney, New South Wales, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

St Vincent's Hospital Melbourne

Melbourne, Victoria, Australia

Lair Centre

Vancouver, British Columbia, Canada

(G.I.R.I.) GI Research Institute

Vancouver, British Columbia, Canada

William Osler Health System

Brampton, Ontario, Canada

St Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

Toronto General Hospital

Toronto, Ontario, Canada

McGill University Health Centre (MUHC)

Montreal, Quebec, Canada

CHU de Québec-Université Laval

Québec, Quebec, Canada

Hopital Henri Mondor

Créteil, , France

Hopital Saint Joseph

Marseille, , France

Hopital Saint Antoine

Paris, , France

zibp - Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH

Berlin, , Germany

Center for HIV and Hepatogastroenterology

Düsseldorf, , Germany

Hannover Medical School

Hanover, , Germany

CIM-Centrum fuer Interdisziplinaere Medizin GmbH

Münster, , Germany

Auckland City Hospital

Auckland, , New Zealand

Calder Center

Auckland, , New Zealand

Christchurch Hospital

Christchurch, , New Zealand

Dunedin Hospital

Dunedin, , New Zealand

Inselspital - Universitaetsspital Bern

Bern, , Switzerland

University Hospital Zurich

Zurich, , Switzerland

Barts Health

London, , United Kingdom

King's College Hospital

London, , United Kingdom

Imperial College Healthcare NHS Trust (St Mary's Hospital)

London, , United Kingdom

Countries

United States; Australia; Canada; France; Germany; New Zealand; Switzerland; United Kingdom

References

Dore GJ, Feld JJ, Thompson A, Martinello M, Muir AJ, Agarwal K, Mullhaupt B, Wedemeyer H, Lacombe K, Matthews GV, Schultz M, Klein M, Hezode C, Mercade GE, Kho D, Petoumenos K, Marks P, Tatsch F, Dos Santos AGP, Gane E; SMART-C Study Group. Simplified monitoring for hepatitis C virus treatment with glecaprevir plus pibrentasvir, a randomised non-inferiority trial. J Hepatol. 2020 Mar;72(3):431-440. doi: 10.1016/j.jhep.2019.10.010. Epub 2019 Oct 23.

Reference Type: DERIVED

PMID: 31655134 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

VHCRP1701

Identifier Type: -

Identifier Source: org_study_id