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Sofosbuvir Plus Ravidasvir for the Treatment of HCV Chronic Infection

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ClinicalTrials.gov Identifier: NCT02961426
Recruitment Status : Recruiting
First Posted : November 11, 2016
Last Update Posted : May 11, 2017
Sponsor:
Collaborator:
Ministry of Health, Malaysia
Information provided by (Responsible Party):
Drugs for Neglected Diseases

Brief Summary:
This is a Phase II/III, multicenter, multi-country, trial to assess the efficacy, safety, tolerance, and pharmacokinetics of sofosbuvir plus ravidasvir for the treatment of HCV infection.

Condition or disease Intervention/treatment Phase
Hepatitis C Drug: sofosbuvir Phase 2 Phase 3

Detailed Description:

The study will assess the efficacy and safety of SOF-RDV across all genotypes, among non-cirrhotic and cirrhotic with CTP class A, interferon/ribavirin naïve or experienced, HCV mono-infected and HCV/HIV co-infected subjects.

It will also study the pharmacokinetics of RDV and, in HCV/HIV co-infected subjects, possible drug-drug interactions with antiretrovirals.

The treatment duration will be 12 weeks for subjects with no cirrhosis (Metavir F0 to F3) and 24 weeks for subjects with compensated cirrhosis (Metavir F4, CTP class A). After enrollment of the first 300 evaluable patients is complete, enrollment will pause while data is being accumulated and analyzed.

After review of interim results by the independent Data and Safety Monitoring Board (DSMB), and by the study Steering Committee, enrollment will resume.

Should modification of the study design be required upon interim analysis, decision will be taken by the study steering committee and the amended protocol or expanded protocol will be submitted to the Ethics Committee for approval.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 750 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open Label Phase II/III, Multicenter, Trial to Assess the Efficacy, Safety, Tolerance, and Pharmacokinetics of Sofosbuvir Plus Ravidasvir in HCV (+/- HIV) Chronically Infected Adults With no or Compensated Cirrhosis in Thailand and Malaysia
Study Start Date : September 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Sofosbuvir

Arm Intervention/treatment
non cirrhotic patient
12 weeks sofosbuvir ravidasvir
Drug: sofosbuvir
combination sofosbuvir ravidasvir treatment for non cirrhotic and compensated cirrhotic patients
Other Name: ravidasvir

compensated cirrhotic patient
24 weeks sofosbuvir ravidasvir
Drug: sofosbuvir
combination sofosbuvir ravidasvir treatment for non cirrhotic and compensated cirrhotic patients
Other Name: ravidasvir




Primary Outcome Measures :
  1. Sustained Virological Response 12 weeks post treatment completion (SVR12), as evidenced by HCV RNA level less than the lower limit of quantification of 15 IU/mL [ Time Frame: Outcome measure of sustained virological response will be assessed 12 weeks after the end of the treatment (SVR 12) as soon as the data will be available ]
    In case of positive HCV RNA, HCV sequences at base line and 12 weeks post treatment completion will be compared to rule out reinfection. Reinfections are not considered as failures



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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:

  • Evidence of chronic HCV infection, defined as:

Positive anti-HCV antibody or detectable HCV RNA or HCV genotype at least 6 months before screening and HCV viral load ≥104 IU/mL at the time of screening In subjects without documented HCV test results 6 months before screening, chronic hepatitis C infection can be assumed if risk exposures occurred > 6 months prior to screening and HCV viral load ≥104 IU/mL at the time of screening.

  • Willing and able to provide written informed consent.
  • Men and women age ≥ 18 years and < 70 years.
  • Body Mass Index (BMI) of 18 to 35 kg/m2.
  • Intention to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments.
  • Women with a negative pregnancy test at screening and baseline.
  • Women of child bearing potential who accept effective contraception from 2 weeks prior to study day 1 until 1 month post-treatment (Double contraceptive method including at least one barrier method). A woman is of non-child bearing potential if she (a)reached natural menopause determined retrospectively after 12 months of amenorrhea without any other obvious medical cause or (b)had procedures like bilateral tubal ligation or hysterectomy or bilateral oophorectomy.
  • Subjects who are compliant in opioid substitution maintenance program may be included as long as there is no concern about study medications adherence and interaction or compliance to study schedules. Active illicit drug users may also be enrolled, as a pre-stratified subpopulation, however their data will not contribute in the primary intent to treat analysis

Exclusion Criteria:

  • Decompensated cirrhosis defined as:

Evidence of advanced stage liver cirrhosis and Child-Turcotte-Pugh (CTP) Class B or C or CTP score >6) or current/past history of decompensation including ascites, variceal bleeding, spontaneous bacterial peritonitis, or hepatic encephalopathy.

  • Hepatocellular carcinoma
  • To exclude hepatocellular carcinoma (HCC), liver imaging within 6 months prior to screening is required for all subjects with cirrhosis and this must continue periodically as in routine HCC surveillance.
  • Additional laboratory exclusion criteria:
  • cirrhotic subjects with albumin < 2.8 g/dL
  • direct bilirubin > 3xULN
  • AST, ALT > 10xULN
  • Low neutrophil count (≤599 cells/mm3), hemoglobin (<9.0 g/dL for male, <8.5 g/dL for female), platelets (<50000 cells/mm3 ) classified as ≥ Grade 3
  • Patients with serum creatinine > 1.5 ULN or end stage renal disease
  • Hepatitis B co-infection (HBsAg positive)
  • Pregnancy, as documented by positive pregnancy tests at screening and baseline
  • Breastfeeding
  • Subjects currently receiving or unable to stop the use for at least 1 week prior to receiving the first dose of study drug any medications or herbal supplements known to be potent inhibitors or moderate inducers of cytochrome P450 (CYP) 3A4 and potent inducers of P-glycoprotein. This includes subjects who are on amiodarone or other contraindicated drugs
  • Participation in other clinical trials within 3 months, except upon agreement with the study steering committee.
  • Any clinically significant findings or unstable condition during the screening, medical history or physical examination that, in the investigator's opinion, would compromise participation in this study . This could include patients with poorly controlled hypertension, asthma, diabetes, or other life-threatening conditions.
  • Current or history of use within the preceding 6 months of immunosuppressive or immune-modulating agents.
  • History of solid organ or bone marrow transplantation.
  • Any prior NS5A inhibitors therapy.
  • Patients with significant cardiovascular conditions including myocardial infarction within the previous 6 months or heart failure NYHA class III or IV; history of Torsade de pointes; QTcF value ≥ 450 milliseconds or third degree heart block;
  • Use of medications associated with QT prolongation concurrently or within the 30 days prior to Screening Visit, including: macrolides, antiarrhythmic agents, azoles, fluoroquinolones, and tricyclic anti-depressants.

Note: An electrocardiogram will be performed at screening and in case of doubt, the subject will be referred to a cardiologist for advice. Subjects will be instructed to immediately consult if they experience dizziness, light headedness or fainting spell.

- HIV/HCV co-infected patients not yet on stable antiretroviral therapy or for whom ART treatment initiation maybe scheduled during the study period.


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): NCT02961426


Contacts
Contact: Lallemand Marc, MD +41 79 293 12 05 mlallemand@dndi.org
Contact: francois simon +41791967868 fsimon@dndi.org

Locations
Malaysia
Department of Medicine/Gastroenterology, Hospital Sultanah Bahiyah Recruiting
Alor Setar, Malaysia
Contact: Datuk Dr Muhammad Radzi Bin Abu Hassan         
Department of Medicine/ Gastroenterology, Hospital Ampang Recruiting
Ampang, Malaysia
Contact: Nur Eliana Eliana Binti Abdul Aziz         
Department of Hepatology, Hospital Selayang Recruiting
Batu Caves Selangor, Malaysia, 68100
Contact: Haniza Omar    +603-61263333 ext 4322      
Department of Medicine/Gastroenterology, University Malaya Medical Centre Recruiting
Kuala Lumpur, Malaysia
Contact: Fong Shu Fen         
Hospital Tengku Ampuan Afzan ,Pusat Penyelidikan Klinikal,Aras Bawah ,Bangunan Pengurusan,Jalan Tanah Putih Recruiting
Kuantan, Malaysia
Contact: Hoi Poh Tee         
Department of Medicine/Infectious Disease, Hospital Sungai Buloh Recruiting
Sungai Buloh, Malaysia
Contact: Suresh Kumar Chindambaram Chindambaram         
Thailand
King Chulalongkorn Memorial Hospital/HIV-NAT, Faculty of Medicine, Chulalongkorn University Recruiting
Bangkok, Thailand, 10330
Contact: Anchalee Avihingsanon    +66 86812 8889    anchaleea2009@gmail.com   
Internal Medicine, Bamrasnaradura Infectious Diseases Institute Recruiting
Bangkok, Thailand, 11000
Contact: Suparat Khemnark, MD    +66 2951 117076    suparatart@gmail.com   
Internal Medicine unit, Medical Department, Nakornping Hospital Recruiting
Chiang Mai, Thailand, 50180
Contact: Kanawee Thetket, MD    +66 5399 9200    kanawee@hotmail.com   
Gastroenterology unit, Department of Internal Medicine, Maharaj Nakorn Chiang Mai Hospital, Faculty of Medicine, Chiang Mai University Recruiting
Chiang Mai, Thailand, 50200
Contact: Satawat Thongsawat, MD    +66 5394 6446    satawat@yahoo.com   
Sponsors and Collaborators
Drugs for Neglected Diseases
Ministry of Health, Malaysia
Investigators
Study Director: Lallemand Marc, MD Drugs for Neglected Diseases
Principal Investigator: Soek-Siam Tan Selayang Hospital

Responsible Party: Drugs for Neglected Diseases
ClinicalTrials.gov Identifier: NCT02961426     History of Changes
Other Study ID Numbers: DNDi-SOF/RDV-01-HCV
First Posted: November 11, 2016    Key Record Dates
Last Update Posted: May 11, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Hepatitis C
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Hepatitis
Liver Diseases
Digestive System Diseases
Sofosbuvir
Antiviral Agents
Anti-Infective Agents