Study to Evaluate the Safety and Efficacy of Daclatasvir/Sofosbuvir/Ribavirin for 16 Versus 24 Weeks for HCV Genotype 3 Cirrhotics

NCT02304159 | Completed Phase 4 Results

• 1 other identifier: AI444284
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, open label, single center safety and efficacy study. At least 40 cirrhotic subjects with HCV genotype 3 will receive standard of care treatment of sofosbuvir and ribavirin (SOF/RBV) as well as 60 mg daily of Daclatasvir (investigational product). Subjects will be randomized in a 1:1 to receive either:

• Group A: 16 weeks of DCV/SOF/RBV
• Group B: 24 weeks of DCV/SOF/RBV Subjects will return to the study center at various time points throughout the 16 or 24 weeks of treatment in addition to 12 weeks post taking last dose of study drug to monitor safety and efficacy. These visits will be according to standard of care.

Conditions

Hepatitis C; Cirrhosis

Keywords

HCV; Genotype 3; Treatment naive; Treatment experienced

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Adverse Events

  This field states the number of participants who had an adverse event

  From baseline (start of study drugs) to last day of taking study drugs; an average of 20 weeks.

• Number of Participants With Abnormal Safety Laboratory Tests (ALT and/or Total Bilirubin) That Required Discontinuing Study Drugs

  This field states the number of participants who had an abnormal ALT that required discontinuing study drugs and/or abnormal Total Bilirubin that required discontinuing study drugs.

  From baseline (start of study drugs) to last day of taking study drugs; an average of 20 weeks.

• Number of Participants With Undetectable HCV Virus 12 Weeks After Stopping Study Drugs

  Sustained Virologic Response (SVR) defined as undetectable HCV RNA 12 weeks after stopping study drugs.

  From baseline (start of study drugs) until 12 weeks after stopping study drugs

Study Arms (2)

Group A - 16 weeks

EXPERIMENTAL

Combination of sofosbuvir 400 mg daily, ribavirin 1000-1200 mg daily (weight based) and daclatasvir 60 mg daily for 16 weeks

Drug: daclatasvir; Drug: Sofosbuvir, Sovaldi; Drug: Ribavirin

Group B - 24 weeks

ACTIVE COMPARATOR

Combination of sofosbuvir 400 mg daily, ribavirin 1000-1200 mg daily (weight based) and daclatasvir 60 mg daily for 24 weeks

Drug: daclatasvir; Drug: Sofosbuvir, Sovaldi; Drug: Ribavirin

Interventions

daclatasvir DRUG

Also known as: DCV, BMS-790052, Daklinza

Group A - 16 weeks; Group B - 24 weeks

Sofosbuvir, Sovaldi DRUG

Also known as: SOF

Group A - 16 weeks; Group B - 24 weeks

Ribavirin DRUG

Also known as: RBV

Group A - 16 weeks; Group B - 24 weeks

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed, written, informed consent must be available from the subject before any study-specific procedures are performed;
• Male or female 18-75 years of age;
• All of the following at least 6 months prior to screening visit:
• Documented HCV infection based on history of a positive serum anti-HCV antibody test and/or detectable levels of HCV RNA \>= 10,000 IU/mL, and
• Documented HCV genotype 3.
• Subjects with evidence of cirrhosis defined by either a liver biopsy \<= 3 years from screening demonstrating a Metavir Fibrosis Score of F4 (or equivalent); OR Fibroscan® \<= 1 year from screening \> 12.5 kPa. If a subject is evaluated by more than one testing method, then the liver biopsy results take precedence;
• Women of childbearing potential (WOCBP) must:
• have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.
• WOCBP must agree to follow instructions for method(s) of contraception for 7 months post-treatment completion.
• Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the following duration for 7 months post-treatment completion.
• Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception. Highly effective methods of contraception have a failure rate of \< 1% per year when used consistently and correctly.
• At minimum the subject agrees to the use of two methods of contraception, with at least one method being highly effective as listed below:
• Highly Effective Methods of Contraception
• Male condoms with spermicide
• Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectables, implants, and intrauterine devices (IUDs) such as Mirena® by male subject's WOCBP partner. Female partners of male subjects participating in the study may use hormone-based contraceptives as one of the acceptable methods of contraception since they will not be receiving study drug. WOCBP cannot use hormonal contraception as one of the two methods of contraception because there are no data on the effectiveness of systemic hormonal contraceptives in women taking SOF. However, WOCBP can continue to use hormonal contraceptives, if necessary, in addition to 2 other non-hormonal methods of contraception

You may not qualify if:

• Subjects who lack capacity to consent for themselves;
• HCV Genotypes other than GT-3 infection; mixed genotype infections are not permitted;
• Liver histology consistent with any other co-existing cause of chronic liver disease (apart from fatty liver and/or Chronic Hepatitis B Virus);
• Body Mass Index \> 40 at the Screening visit;
• Any of the following within one month of screening:
• Uncontrolled diabetes;
• Any of the following within 6 months of screening visit, any of the following:
• Decompensated liver disease, esophageal variceal bleeding, or a hepatic mass lesion suspicious for hepatocellular carcinoma (HCC);
• Subjects who have been treated for HCV infection;
• History of unstable or deteriorating cardiovascular or cerebrovascular disease;
• Alcohol and/or drug.
• QTcF ≥ 500 ms at the baseline visit.
• Any of the following laboratory abnormalities within 8 weeks of the baseline visit:
• Hemoglobin \<8 g/dL;
• Absolute neutrophil count \<0.50 x 103 cells/μL;

Sponsors & Collaborators

• Tarek I. Hassanein, M.D., FACP, FAG, AGAF: lead

Study Sites (1)

Southern California Research Center

Coronado, California, 92118, United States

Location

MeSH Terms

Conditions

Hepatitis C; Fibrosis

Interventions

daclatasvir; Sofosbuvir; Ribavirin

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; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Ribonucleosides; Nucleosides

Limitations and Caveats

Study received IND approval in November 2014. Daclatasvir received initial FDA approval in July 2015. Participants were randomized to receive daclatasvir for either 16 or 24 weeks and were followed per standard of care.

Results Point of Contact

• Title: Dr. Tarek Hassanein
• Organization: Southern California Research Center

thassanein@livercenters.com

619-319-3993

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: President

Study Record Dates

• First Submitted: November 17, 2014
• First Posted: December 1, 2014
• Study Start: January 1, 2015
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: April 24, 2019
• Results First Posted: April 24, 2019

Record last verified: 2019-04

Locations

US (1)