Hepatitis C
Conditions
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.
Detailed description
This is a Phase II/III, multicenter, multi-country trial to assess the efficacy, safety, tolerance and pharmacokinetics of SOF-RDV for the treatment of HCV infection, across genotypes 1,2,3,6, 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). The study is performed in 2 stages. Stage 1 has been completed. Efficacy and safety results from Stage 1 were reviewed and approved by the independent Data and Safety Monitoring Board (DSMB) which provided the recommendation to proceed with the study stage 2. On-going stage 2 aims to supplement Stage 1 results and provide additional information on the performance of SOF-RDV in the main genotypes found in Malaysia and Thailand.
Interventions
DRUGsofosbuvir + ravidasvir
combination of sofosbuvir + ravidasvir
Sponsors
Ministry of Health, Malaysia
Ministry of Health, Thailand
National Science and Technology Development Agency, Thailand
Drugs for Neglected Diseases
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
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 ≥10\^4 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 ≥10\^4 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 a highly effective contraceptive method from at least 2 weeks prior to study day 1 until 1-month post-treatment. 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 an opioid substitution maintenance program (e.g. with methadone or buprenorphine) may be included as long as there is no concern about study medications adherence and interaction or compliance to study schedules. * Inclusion criteria related to HIV/HCV co-infected patients: * HIV/HCV co-infected patients receiving cART fulfilling the below criteria are eligible for the study: Antiretroviral therapy (ART) should have been initiated at least 6 months prior to screening / Patient has to have been on the same protocol-approved ARV regimen for ≥ 8 weeks prior to screening and is expected to continue the current ARV regimen through the end of study / HIV ARVs: agents allowed in this study should be administered per the prescribing information in the package insert / Screening HIV RNA \< 50 copies/mL / Screening CD4 cell count ≥ 100 cells/uL * HIV/HCV co-infected patients not receiving cART: Screening CD4 cell count must be ≥ 500 cells/uL
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: for all patients with cirrhosis, hepatocellular carcinoma (HCC), should be excluded by liver imaging within 6 months prior to screening, and this must continue periodically as in routine HCC surveillance. * Laboratory
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Virological Response at 12 weeks post treatment completion (SVR12), as evidenced by HCV RNA level less than the lower limit of quantification | 12 weeks after the end of the study treatment | Related objective: to assess the efficacy of sofosbuvir-ravidasvir (SOF-RDV) at 12 weeks after the end of study treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of on-treatment virologic failure among subjects not achieving SVR12 | 12 weeks after the end of the study treatment | Defined as HCV RNA ≥ LLOQ at the end of the treatment period. Related objective: to assess the efficacy of SOF-RDV 12 weeks after the end of study treatment. |
| Occurrence of virologic breakthrough among subjects not achieving SVR12 | 12 weeks after the end of the study treatment | Defined as either confirmed ≥ 1 log10 IU/mL increase in HCV RNA from nadir while on treatment or confirmed HCV RNA ≥ LLOQ if HCV RNA previously declined to \< LLOQ while on treatment. Related objective: to assess the efficacy of SOF-RDV 12 weeks after the end of study treatment. |
| Occurrence of virologic relapse among subjects not achieving SVR12 | 12 weeks after the end of the study treatment | Defined as HCV RNA \< LLOQ at the end of the treatment period but HCV RNA ≥ LLOQ during the post-treatment period. Related objective: to assess the efficacy of SOF-RDV 12 weeks after the end of study treatment. |
| Occurrence of non-virologic failure among subjects not achieving SVR12 | 12 weeks after the end of the study treatment | Defined as any failure that does not meet the virologic failure criteria (e.g. adverse event, lost to follow-up). Related objective: to assess the efficacy of SOF-RDV 12 weeks after the end of study treatment. |
| Occurrence of premature treatment discontinuation and occurrence of premature study discontinuation (overall and by reason for premature discontinuation) | Through study completion (up to 36 weeks for non-cirrhotic patients and up to 48 weeks for cirrhotic patients) | Related objective: to assess the safety of SOF-RDV |
| Time to premature treatment discontinuation and time to premature study discontinuation | Through study completion (up to 36 weeks for non-cirrhotic patients and up to 48 weeks for cirrhotic patients) | Related objective: to assess the safety of SOF-RDV |
| Sustained virologic response at 4 and 24 weeks post treatment completion (SVR4 and SVR24), as evidenced by HCV RNA level less than the lower limit of quantification | 4 and 24 weeks after the end of the study treatment | Related objective: to assess the efficacy of SOF-RDV at 4 and 24 weeks after the end of study treatment |
| Time to first TEAE, time to first grade 3/4 TEAE and time to first TESAE | Through study completion (up to 36 weeks for non-cirrhotic patients and up to 48 weeks for cirrhotic patients) | Related objective: to assess the safety of SOF-RDV. TEAE: Treatment Emergent Adverse Event TESAE: Treatment Emergent Serious Adverse Event |
| Maximum plasma concentration (Cmax) of ravidasvir (and sofosbuvir if needed) | Intensive PK (stage 1 only): 4 weeks after treatment initiation; Sparse PK: 4, 8 and 12 weeks after treatment initiation | Related objective: to study the pharmacokinetics (PK) of SOF and RDV and to evaluate potential drug-drug interactions with antiretrovirals and, as needed, interactions with concomitant prescribed or non-prescribed drugs. |
| Baseline factors associated with SVR12 outcome | Baseline and 12 weeks after the end of the study treatment | Related objective: to describe the subjects' demographic, clinical and biological characteristics and their relationship with SVR12. |
| Change in the PROQOL-HCV domain scores from treatment initiation to 12 weeks after treatment completion | 12 weeks after the end of the study treatment | Related objective: to assess the subjects' quality of life before and after therapy. PROQOL-HCV: Patient Reported Outcome Quality of Life survey for HCV, questionnaire that evaluates 7 domains, each domain scores range 0 to 100, where 100 corresponds to the best quality of life. |
| Changes in HCV NS5A sequences from treatment initiation in subjects not achieving SVR12 | 12 weeks after the end of the study treatment | Related objective: to evaluate the presence of viral resistance-associated variants (RAVs) to SOF-RDV in patients with virological failure 12 weeks after treatment completion |
| Occurrence of the following events: TEAE, TEAE considered to be at least possibly related to at least one of the study drugs, TEAE leading to premature treatment discontinuation, TE laboratory abnormality, grade 3/4 TEAE, TESAE and death | Through study completion (up to 36 weeks for non-cirrhotic patients and up to 48 weeks for cirrhotic patients) | Related objective: to assess the safety of SOF-RDV. TEAE: Treatment Emergent Adverse Event TESAE: Treatment Emergent Serious Adverse Event |
Countries
Malaysia, Thailand
Outcome results
None listed