Triple or Quadruple Combination DAAs Treatment for Subjects With HCV GT 1b Infection

NCT03794258 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: H&H_YANGTZE_1
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 2a, open-label, randomized study. The study is designed to test the hypothesis that the nucleoside inhibitor sofosbuvir combined with NS5A inhibitor daclatasvir and NS5B non-nucleoside inhibitor CDI-31244 with/without the protease inhibitor asunaprevir will result in high SVR rate with a shortened treatment duration (2 weeks) in non-cirrhotic HCV genotype 1b-infected subjects.

Conditions

HCV Infection

Outcome Measures

Primary Outcomes (1)

• Proportion of participants with sustained virologic response 12 weeks after discontinuation of therapy (SVR12)

  SVR12 is defined as HCV RNA \< lower limit of quantification (LLOQ) 12 weeks after last dose of study drug.

  Post treatment Week 12

Secondary Outcomes (4)

• Frequency and severity of adverse events

  Baseline up to Week 24

• Proportion of participants with unquantifiable HCV viral load at specified time points during and after treatment

  Baseline up to Week 24

• HCV RNA levels and change during and after treatment

  Baseline up to Week 24

• Proportion of participants with on-treatment virologic breakthrough and relapse

  Baseline up to Week 24

Study Arms (2)

SOF+DCV+CDI-31244

EXPERIMENTAL

Subjects will receive two weeks of sofosbuvir, daclatasvir, and CDI-31244 if they achieve HCV RNA \< 500 IU/mL on Day 2 and HCV RNA \< LLOQ (\< 25 IU/mL) on Week 1.

Drug: SOF+DCV+CDI-31244

SOF+DCV+CDI-31244+ASV

EXPERIMENTAL

Subjects will receive two weeks of sofosbuvir, daclatasvir, CDI-31244 and asunaprevir if they achieve HCV RNA \< 500 IU/mL on Day 2 and HCV RNA \< LLOQ (\< 25 IU/mL) on Week 1.

Drug: SOF+DCV+CDI-31244+ASV

Interventions

SOF+DCV+CDI-31244 DRUG

Sofosbuvir (SOF) 400 mg administered orally once daily; Daclatasvir (DCV) 60 mg administered orally once daily; CDI-31244 400 mg administered orally once daily.

SOF+DCV+CDI-31244

SOF+DCV+CDI-31244+ASV DRUG

Sofosbuvir (SOF) 400 mg administered orally once daily; Daclatasvir (DCV) 60 mg administered orally once daily; CDI-31244 400 mg orally once daily; Asunaprevir (ASV) 200mg administered orally twice daily.

SOF+DCV+CDI-31244+ASV

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent.
• Male or female, age 18-70 years.
• HCV genotype 1b infection as determined by the Laboratory. Any non-definitive results will exclude the subject from study participation.
• HCV RNA level ≥ 10,000 IU/mL and \< 10,000,000 IU/mL.
• No evidence of cirrhosis. Cirrhosis defined as any 1 of the following, within 6 months of study entry:
• Liver biopsy showing cirrhosis;
• Fibroscan showing cirrhosis or results \>12.5 kPa;
• FibroTest® score \>0.75 and an aspartate aminotransferase (AST): platelet ratio index (APRI) \>2 during screening.
• Subjects must have the following laboratory parameters at screening:
• ALT ≤ 10 x the upper limit of normal (ULN);
• AST ≤ 10 x ULN;
• Direct bilirubin ≤1.5 x ULN;
• Platelets ≥ 50,000;
• HbA1c ≤ 8.5%;
• Creatinine clearance (CLcr) ≥ 60 mL /min, as calculated by the Cockcroft-Gault equation;

You may not qualify if:

• Child-Pugh scoring of B and C.
• Creatinine Clearance \< 30ml/min.
• Mixed HCV genotypes.
• Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV).
• Hepatocellular carcinoma or other malignancy (with exception of certain resolved skin cancers).
• Current or prior history of any of the following:
• Clinically-significant illness (other than HCV) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol; subjects currently under evaluation for a potentially clinically-significant illness (other than HCV) are also excluded.
• Gastrointestinal disorder or post operative condition that could interfere with the absorption of the study drug.
• Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy.
• Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage).
• Solid organ transplantation.
• Significant pulmonary disease, significant cardiac disease or porphyria.
• Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within the last 5 years. Subjects with psychiatric illness that is well-controlled on a stable treatment regimen for at least 12 months prior to randomization or has not required medication in the last 12 months may be included.
• Malignancy diagnosed or treated within 5 years (recent localized treatment of squamous or non-invasive basal cell skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to screening); subjects under evaluation for malignancy are not eligible.
• Significant drug allergy (such as anaphylaxis or hepatotoxicity).

Sponsors & Collaborators

• Humanity & Health Medical Group Limited: lead

Study Sites (1)

Humanity & Health Research Centre

Hong Kong, Hong Kong SAR, Hong Kong

Location

MeSH Terms

Conditions

Hepatitis C

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

Study Officials

• Georg Lau, MD

  Humanity & Health Research Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2019
• First Posted: January 7, 2019
• Study Start: May 1, 2019
• Primary Completion: April 15, 2020
• Study Completion: April 30, 2020
• Last Updated: May 7, 2020

Record last verified: 2020-05

Locations

HK (1)