CTRI/2023/11/059507 [Registered on: 03/11/2023] Trial Registered Prospectively
Last Modified On:
27/05/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
to study safety and efficacy of Bemnifosbuvir (bem) and Ruzasvir (rzr)
Scientific Title of Study
A phase 2, open-label study to assess the safety and efficacy of Bemnifosbuvir (bem) and Ruzasvir (rzr) in subjects with chronic hepatitis c virus (hcv) infection
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
2022-502868-21-00
EudraCT
AT-01B-004 version 1, 09 Jan 2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Australia Brazil Canada Egypt Germany India Indonesia Malaysia Mauritius Pakistan Philippines Republic of Korea Republic of Moldova Romania Singapore South Africa Spain Thailand Turkey Viet Nam
Fortis Escorts Heart Institute, Escorts Heart Institute and Research Centre Ltd, Okhla Road, New Delhi-110025, India
Submittted/Under Review
Human Research Ethics Committee, Indian Institute of Liver & Digestive Sciences (HREC, IILDS) , Sitala East, Malipukuria, Jagadishpur, Sonarpur South,24 Parganas, Kolkata-700150, West Bengal, India
Approved
Institutional Ethics Committee, KLE University, KLE Dr. Prabhakar Kore Hospital and Medical Research Centre, Nehru Nagar, Belgavi-590010, Karnataka, India.
Approved
Lokmanya Tilak Muncipal Medical College and Lokmanya Tilak Municipal General Hospital, Department of Gestroentrology, Sion, Mumbai-400022, Maharashtra, India.
Submittted/Under Review
Midas Multispeciality Hospital, Midas Heights, 07, Central Bazar Road, Ramdaspeth, Nagpur-440010, Maharashtra, India
Approved
Seth G. S. Medical College King Edward Memorial Hospital, Department of Gastroenterology, Acharya Donde Marg, Parel, Mumbai-400012, Maharastra, India.
Approved
Shree Giriraj Multispeciality Hospital, A unit of Shree Giriraj Lifecare Pvt Ltd, 27-Navjyot Park, 150 Feet Ring Road, Rajkot-360005 Gujarat, India.
Approved
Unity Hospital Ethics Committee, Unity Trauma Center And ICU, N-4 Janki Park Society, Aai Mata Road, Paravat Patiya, Surat-395010, Gujarat, India.
Duration is 8 weeks
Subjects will take 550 mg BEM (as 2 x 275-mg tablets) and 180 mg RZR (as 2 x 90-mg capsules) once daily for 8 weeks
Study drugs will be taken together orally
Comparator Agent
NA
NA
Inclusion Criteria
Age From
18.00 Year(s)
Age To
85.00 Year(s)
Gender
Both
Details
- Willing and able to provide written informed consent
- Male or female subjects between ≥ 18 years of age (or the legal age of consent per local regulations) and ≤ 85 years of age
- Fridericia-corrected QT (QTcF) interval ≤ 440 ms for males and ≤ 460 ms for females at Screening Note: The mean of the triplicate readings should be used to assess the QTcF.
- Female subjects of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or to the use of an acceptable effective contraception, as described in Section 5.9
- Females must have a negative pregnancy test at Screening and at Day 1 prior to dosing
- Subjects must be direct-acting antiviral (DAA)-treatment-naïve, defined as never exposed to an approved or experimental DAA for HCV Note: Prior exposure to (peg)interferon with or without ribavirin is acceptable, as long as it/they were not administered with a DAA.
-Subjects must have HCV GT1, GT2, GT3, GT4, GT5, GT6, or GT7 (with no evidence of non-typeable or mixed GT), documented at Screening.
- Documented medical history compatible with chronic HCV, including any one of the following:
- positive for anti-HCV antibody, HCV RNA, or an HCV GT at least 6 months prior to Day 1, or
-positive for anti-HCV antibody at Screening with clinical or laboratory evidence of chronic HCV disease, such as the presence of fibrosis by biopsy or noninvasive tests
- HCV RNA ≥ 1,000 IU/mL at Screening.
- Liver disease staging assessment as follows:
-Absence of cirrhosis (F0 to F3) defined as any one of the following:
− Liver biopsy within 24 months of Day 1 showing absence of cirrhosis
− Fibroscan® within 12 months of Day 1 with a result of ≤ 12.5 kPa
− Fibrosure® (Fibrotest®) performed during screening with a score of ≤ 0.48 and an aspartate aminotransferase (AST)-to-platelet ratio index (APRI) of ≤ 1
-Compensated cirrhosis (F4) defined as any one of the following:
− Liver biopsy performed prior to Day 1 showing cirrhosis (Metavir stage 4 or equivalent)
− Fibroscan® within 12 months of Day 1 showing cirrhosis with result > 12.5 kPa
− Fibrosure® (Fibrotest®) performed during screening with a score of > 0.75 and an APRI of > 2 APRI formula: AST ÷ lab upper limit of normal (ULN) for AST × 100 ÷ (platelet count ÷ 100). NOTE: In the absence of a definitive diagnosis of presence or absence of cirrhosis by the above criteria, a liver biopsy or Fibroscan® is required. Liver biopsy results supersede the results obtained by Fibroscan® or Fibrosure®.
- Subject is, in the opinion of the investigator, willing and able to comply with the study drug regimen and all other study requirements
ExclusionCriteria
Details
- Female subject is pregnant or breastfeeding
-Co-infected with hepatitis B virus (HBV; positive for hepatitis B surface antigen [HBsAg]) and/or human immunodeficiency virus (HIV)
-Abuse of alcohol and/or illicit drug use that could interfere with adherence to study requirements as judged by the investigator
-Prior exposure to any HCV DAA
-Requirement of any prohibited medications, as described in Section 5.8
-Use of other investigational drugs within 30 days of dosing or plans to enroll in another clinical trial of an investigational agent while participating in the present study
-Subject with known allergy to the study medications or any of their components
-History or signs of decompensated liver disease: ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, or other clinical signs of portal hypertension or hepatic insufficiency
- Cirrhotic and has a Child-Pugh score >6, corresponding to a Child-Pugh Class B or C Note: To calculate the Child-Pugh score, refer to the following website: https://www.mdcalc.com/calc/340/child-pugh-score-cirrhosis-mortality
-History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC
-Active clinically significant diseases including:
-Evidence of history of chronic hepatitis not caused by HCV, including drug-induced hepatitis, hemochromatosis, Wilson’s disease, alpha-1-antitrypsin deficiency, alcoholic liver disease, and autoimmune hepatitis
-Cardiac abnormalities/dysfunction that may interfere with subject treatment, assessment, or compliance with the protocol, including unstable angina, unstable congestive heart failure, and unstable arrhythmia
-Malignant disease or suspicion or history of malignant disease within previous 5 years (except for adequately treated basal or basosquamous cell carcinoma)
-Any medical condition requiring chronic use of systemic corticosteroids or other immunosuppressive drugs (e.g., for organ transplantation or autoimmune conditions). Note: Topical or inhaled corticosteroids are permitted.
-Subject with intestinal malabsorption (e.g., structural defects, digestive failure, or enzyme deficiencies, with the exception of lactose intolerance)
-Any other clinically significant medical condition that, in the opinion of the investigator, would jeopardize the safety of the subject or impact the validity of the study results
- Clinically significant abnormal ECG at Screening, as determined by the investigator.
- Any of the following laboratory parameters at Screening:
-Alanine aminotransferase (ALT) or AST > 10 x ULN
-Total bilirubin > 3 mg/dL (> 51.3 μmol/L)
-Albumin < 2.8 g/dL (< 28 g/L)
-International Normalized Ratio (INR) > 2.2 unless subject has a stable INR on an anticoagulant
-Hemoglobin < 10 g/dL
-Hemoglobin A1c (HbA1c) > 8.5%
-Platelet count < 50 x 109/L
-Estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73 m2 as estimated by the Modification of Diet in Renal Disease (MDRD) formula
Note: Retests of Screening laboratory parameters or assessments may be permitted once in certain scenarios with medical monitor approval. Such scenarios may include lab processing error, results inconsistent with subject’s historical values/medical history, or other extenuating circumstances such as a recent or intercurrent illness potentially affecting Screening laboratory results
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
- To evaluate the safety and tolerability of BEM + RZR
-To evaluate the efficacy of BEM + RZR as assessed by the proportion of subjects achieving SVR12
The primary efficacy endpoint is SVR12.
Secondary Outcome
Outcome
TimePoints
NA
NA
Target Sample Size
Total Sample Size="280" Sample Size from India="30" Final Enrollment numbers achieved (Total)= "275" Final Enrollment numbers achieved (India)="4"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is an open-label trial to
evaluate 8 weeks of treatment with BEM + RZR in subjects with chronic HCV
infection. Approximately 280 treatment-naïve subjects with genotype (GT) 1, 2,
3, 4, 5, 6 or 7, either without cirrhosis or with compensated cirrhosis, will be
enrolled.
A lead-in group of 60 non-cirrhotic
subjects will initially be enrolled. At 4 weeks posttreatment, this lead-in
group will be evaluated for safety, sustained virologic response at 4 weeks
posttreatment (SVR4) and virologic relapse; enrollment will open to the
remaining 220 subjects provided that ≤ 6 subjects in the lead-in group (from
the per-protocol [PP] population) experience virologic failure and no study
stopping rules are met.
Subjects will be screened for up to
4 weeks, although this can be extended for up to 6 weeks for extenuating
circumstances with Sponsor approval.
Eligible subjects will enter the
treatment period and receive BEM + RZR for 8 weeks. After Day 1, during the
treatment period, subjects may self-administer study drugs (ie, investigational
medicinal product [IMP]) at home, with the exception of subjects who agree to
additional blood sampling as part of up to 2 substudies. These subjects will be
required to take their study drug in the clinic on certain days. Subjects will
return to the clinic for evaluations at Weeks 1, 2, 4, 6 and 8 (End of
Treatment [EOT]) during the treatment period.
Following their last visit of the
treatment period (including subjects who prematurely discontinue treatment),
subjects will enter the Follow-up period and return to the clinic for
evaluations at Follow-up Weeks 4, 12, and 24. End-of-Study (EOS) is defined as
the visit at 24 weeks posttreatment.
Adverse events (AEs) and
concomitant medications will be reviewed during visits throughout the treatment
and follow-up periods. Subjects may also be contacted between visits to assess
their compliance with the dosing regimen (during the treatment period) and to
discuss AEs and concomitant medications.
The primary endpoint is SVR12. Secondary
endpoints include virologic failure and SVR24. Exploratory endpoints are
resistance to either study drug (BEM or RZR), SVR12 in subgroups defined by
demographics and/or baseline characteristics, HCV RNA changes from baseline and
exposure-response relationships. Safety endpoints are the incidence of AEs,
serious adverse events (SAEs), and AEs resulting in treatment discontinuation;
clinical laboratory abnormalities; vital sign measurements; and
electrocardiogram (ECG) parameters.
There will be two substudies (PK only; PK-VK),
each requiring separate consent; up to 50 subjects can consent to either or
both. Subjects who consent to the PK-only substudy will provide additional
blood samples at any planned treatment visit as early as Week 2 based on convenience
for subject and investigator. Subjects who consent to the PK-VK substudy will
provide additional blood samples a) on Day 1; and b) on Days 2 and 3 (24 and 48
hours after the first dose; ± 2 hours). Study drug will be administered at the
clinic on these days