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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03794258
Recruitment Status : Withdrawn (Can not recruit the patients due to the pandemic of COVID-19)
First Posted : January 7, 2019
Last Update Posted : May 7, 2020
Sponsor:
Information provided by (Responsible Party):
Humanity & Health Medical Group Limited

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.

Condition or disease Intervention/treatment Phase
HCV Infection Drug: SOF+DCV+CDI-31244 Drug: SOF+DCV+CDI-31244+ASV Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2a, Open-label, Randomized Study of the Safety and Preliminary Efficacy of Triple or Quadruple Combination DAAs With Ultra-short Duration Therapy in Subjects With HCV Genotype 1b Infection (YANGTZE Study)
Actual Study Start Date : May 1, 2019
Actual Primary Completion Date : April 15, 2020
Actual Study Completion Date : April 30, 2020

Arm Intervention/treatment
Experimental: SOF+DCV+CDI-31244
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
Sofosbuvir (SOF) 400 mg administered orally once daily; Daclatasvir (DCV) 60 mg administered orally once daily; CDI-31244 400 mg administered orally once daily.

Experimental: SOF+DCV+CDI-31244+ASV
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
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.




Primary Outcome Measures :
  1. Proportion of participants with sustained virologic response 12 weeks after discontinuation of therapy (SVR12) [ Time Frame: Post treatment Week 12 ]
    SVR12 is defined as HCV RNA < lower limit of quantification (LLOQ) 12 weeks after last dose of study drug.


Secondary Outcome Measures :
  1. Frequency and severity of adverse events [ Time Frame: Baseline up to Week 24 ]
  2. Proportion of participants with unquantifiable HCV viral load at specified time points during and after treatment [ Time Frame: Baseline up to Week 24 ]
  3. HCV RNA levels and change during and after treatment [ Time Frame: Baseline up to Week 24 ]
  4. Proportion of participants with on-treatment virologic breakthrough and relapse [ Time Frame: Baseline up to Week 24 ]
    Viral breakthrough is defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) during treatment, but did not achieve a sustained virologic response (SVR). Viral relapse is defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) within 4 weeks of end of treatment, but did not achieve an SVR.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Willing and able to provide written informed consent.
  2. Male or female, age 18-70 years.
  3. HCV genotype 1b infection as determined by the Laboratory. Any non-definitive results will exclude the subject from study participation.
  4. HCV RNA level ≥ 10,000 IU/mL and < 10,000,000 IU/mL.
  5. No evidence of cirrhosis. Cirrhosis defined as any 1 of the following, within 6 months of study entry:

    1. Liver biopsy showing cirrhosis;
    2. Fibroscan showing cirrhosis or results >12.5 kPa;
    3. FibroTest® score >0.75 and an aspartate aminotransferase (AST): platelet ratio index (APRI) >2 during screening.
  6. Subjects must have the following laboratory parameters at screening:

    1. ALT ≤ 10 x the upper limit of normal (ULN);
    2. AST ≤ 10 x ULN;
    3. Direct bilirubin ≤1.5 x ULN;
    4. Platelets ≥ 50,000;
    5. HbA1c ≤ 8.5%;
    6. Creatinine clearance (CLcr) ≥ 60 mL /min, as calculated by the Cockcroft-Gault equation;
    7. Hemoglobin ≥ 11 g/dL for female subjects; ≥ 12 g/dL for male subjects;
    8. Albumin ≥ 3g/dL;
    9. INR ≤ 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR.
  7. Subject has not been treated with any investigational drug or device within 30 days of the Screening visit.
  8. A female subject is eligible to enter the study if it is confirmed that she is:

    1. Not pregnant or nursing;
    2. Of non-childbearing potential (i.e., women who have had a hysterectomy, have both ovaries removed or medically documented ovarian failure, or are postmenopausal - women > 50 years of age with cessation (for ≥12 months) of previously occurring menses), or
    3. Of childbearing potential (i.e., women who have not had a hysterectomy, both ovaries removed, or no medically documented ovarian failure) based on the following conditions.

    Women ≤ 50 years of age with amenorrhea will be considered to be of childbearing potential. These women must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on the Baseline/Day 0 visit prior to randomization. They must also agree to one of the following from 3 weeks prior to Baseline/Day 0 until 4 months after last dose of the triple/quadruple therapies:

    - Complete abstinence from intercourse. Periodic abstinence from intercourse (e.g., calendar, ovulation, symptothermal, post-ovulation methods) is not permitted.

    Or

    • Consistent and correct use of 1 of the following methods of birth control listed below in addition to a male partner who correctly uses a condom from 3 weeks prior to Baseline/Day 0 until 4 months after last dose of the triple/quadruple therapies. Women of childbearing potential must not rely only on hormone-containing contraceptives as a form of birth control during the study. Female subjects using a hormone-containing contraceptive prior to Screening may continue their contraceptive regimen in addition to the study specified methods of birth control.
    • intrauterine device (IUD) with a failure rate of <1% per year
    • female barrier method: cervical cap or diaphragm with spermicidal agent
    • tubal sterilization
    • vasectomy in male partner
  9. All male study participants must agree to consistently and correctly use a condom, while their female partner agrees to use either 1 of the non-hormonal methods of birth control listed above or a hormone-containing contraceptive listed below, from the date of Screening until 4 months after their last dose of the triple/quadruple therapies:

    • implants of levonorgestrel
    • injectable progesterone
    • oral contraceptives (either combined or progesterone only)
    • contraceptive vaginal ring
    • transdermal contraceptive patch
  10. Male subjects must agree to refrain from sperm donation from the date of screening until at least 4 months after the last dose of the triple therapies.
  11. Subject must be of generally good health, with the exception of chronic HCV infection, as determined by the Investigator.
  12. Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments.
  13. Screening ECG without clinically significant abnormalities.

Exclusion Criteria:

  1. Child-Pugh scoring of B and C.
  2. Creatinine Clearance < 30ml/min.
  3. Mixed HCV genotypes.
  4. Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV).
  5. Hepatocellular carcinoma or other malignancy (with exception of certain resolved skin cancers).
  6. Current or prior history of any of the following:

    1. 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.
    2. Gastrointestinal disorder or post operative condition that could interfere with the absorption of the study drug.
    3. Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy.
    4. Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage).
    5. Solid organ transplantation.
    6. Significant pulmonary disease, significant cardiac disease or porphyria.
    7. 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.
    8. 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.
    9. Significant drug allergy (such as anaphylaxis or hepatotoxicity).
    10. History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the subject's participation for the full duration of the study, such that it is not in the best interest of the subject to participate
  7. Pregnant or nursing female or male with pregnant female partner.
  8. Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, cholangitis).
  9. Donation or loss of more than 400 mL blood within 2 months prior to Baseline/Day 1.
  10. Clinically-relevant drug abuse within 12 months of screening. A positive drug screen will exclude subjects unless it can be explained by a prescribed medication; the diagnosis and prescription must be approved by the investigator.
  11. Active or recent history (≤ 1 year) of drug or alcohol abuse.
  12. Use of any following drugs that might interact with the study drugs.

    1. Treatment with amiodarone within 180 days before study entry;
    2. Treatment with digoxin within 30 days before study entry;
    3. Treatment with rifabutin, rifampin, rifapentine, phenytoin, phenobarbital, St. John's wort, carbamazepine, oxcarbazepine, rosuvastatin, or atorvastatin within 10 days before study entry. However, switching to another statin is acceptable.
  13. Screening or baseline electrocardiogram (ECG) with clinically significant findings.
  14. QTcF (QT interval corrected using Fridericia's formula) > 450 msec at screening.
  15. Chronic use of systemically administered immunosuppressive agents (e.g., prednisone equivalent > 10 mg/day).
  16. Known hypersensitivity to sofosbuvir, daclatasvir, CDI-31244 and asunaprevir or formulation recipients.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03794258


Locations
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Hong Kong
Humanity & Health Research Centre
Hong Kong, Hong Kong SAR, Hong Kong
Sponsors and Collaborators
Humanity & Health Medical Group Limited
Investigators
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Principal Investigator: Georg Lau, MD Humanity & Health Research Centre
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Responsible Party: Humanity & Health Medical Group Limited
ClinicalTrials.gov Identifier: NCT03794258    
Other Study ID Numbers: H&H_YANGTZE_1
First Posted: January 7, 2019    Key Record Dates
Last Update Posted: May 7, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Hepatitis C
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Hepatitis
Liver Diseases
Digestive System Diseases