Re-treatment of HCV Following DAA Failure

NCT03483987 | Terminated

• 1 other identifier: 2017-202-IP-100
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

HCV infection is treated with oral drugs, termed as 'direct-acting anti-viral agents' (DAAs). In India, four DAAs are available (sofosbuvir \[SOF\], daclatasvir \[DCV\], ledipasvir \[LDV\] and velpatasvir \[VEL\]). Globally, DAA based regimens have obtained excellent rates of cure. Cure of HCV infection is defined as undetectable HCV RNA 12 weeks after stopping drugs, also referred to as sustained virological response at week 12 (SVR12). Using these DAA based treatment regimens, a small number (up to 5%) of people fail to achieve SVR12 and HCV RNA reappear after a few weeks of stopping the drugs (virological relapse). Data on management of virological relapse are extremely limited, especially in genotype 3, and no guidelines exist regarding re-treatment options for such group. Hence, we plan to re-treat such people using what appear to be the best combination treatment in each situation and to review our experience over time. Participants with chronic HCV infection who relapsed following standard DAA-based treatment regimen will be invited to participate. We propose to re-treat them with the anti-HCV drug combination which appears to be the most suited to his/her clinical profile, based on the current empiric knowledge - the choice of drugs will be based on HCV genotype, the previous treatment regimen and the presence/absence of liver cirrhosis, etc. During anti-HCV treatment, participants will be given expected standard of care and HCV RNA will be tested at 4-week intervals starting from week 4 and till RNA becomes undetectable, and then at the end of treatment and 12 weeks after the treatment was stopped - as is the usual practice during such treatment. Relevant clinical, laboratory and treatment details will be recorded in a pre-defined data collection form. Treatment outcome will be categorized as success (SVR12), treatment failure (any detectable HCV RNA at the end of 24 weeks treatment duration) or relapse (HCV RNA negative at the end of treatment, but positive at 12 weeks after stopping treatment). If possible, a 5-ml blood specimen will be collected before starting re-treatment from all participants; in addition, another similar specimen will be collected following the treatment in those in whom the re-treatment is unsuccessful. These will be stored and may be used in future for virological studies to look for drug-resistance variations.

Conditions

Chronic Hepatitis C

Keywords

Hepatitis c virus; Direct acting antiviral drugs; Virological relapse

Outcome Measures

Primary Outcomes (1)

• SVR12

  Proportion of participants with undetectable HCV RNA at 12 weeks after stopping DAA-based HCV re-treatment

  - 12 weeks after stopping 24 weeks of DAA based treatment

Study Arms (6)

Sof+Ledi+R arm

EXPERIMENTAL

Participants with HCV genotype 1,4, 5 or 6 and relapsed with following regimens will be treated with sofosbuvir, ledipasvir and ribavirin combination 1. Sofosbuvir plus velpatasvir with or without ribavirin for 12 weeks 2. Sofosbuvir plus ribavirin with or without pegylated interferon for 12 or 24 weeks 3. Sofosbuvir plus velpatasvir with or without ribavirin for 24 weeks and are not eligible for pegylated interferon

Drug: Sof+Ledi+R arm

Sof+Ledi+R+Peg-IFN arm

EXPERIMENTAL

Participants with HCV genotype 1,4, 5 or 6, who have relapsed after a 24 weeks treatment regimen of sofosbuvir plus velpatasvir with or without ribavirin combination and are eligible for pegylated interferon, will be treated with a combination of sofosbuvir, ledipasvir, ribavirin plus pegylated interferon

Drug: Sof+Ledi+R+Peg-IFN arm

Sof+Dacla+R arm

EXPERIMENTAL

Participants with HCV genotype 2 or 3 and relapsed with following regimens will be treated with a combination of sofosbuvir, daclatasvir and ribavirin 1. Sofosbuvir plus velpatasvir with or without ribavirin for 12 weeks 2. Sofosbuvir plus ribavirin with or without pegylated interferon for 12 or 24 weeks 3. Sofosbuvir plus velpatasvir with or without ribavirin for 24 weeks and are not eligible for pegylated interferon

Drug: Sof+Dacla+R arm

Sof+Dacla+R+Peg-IFN arm

EXPERIMENTAL

Participants with HCV genotype 2 or 3, who have relapsed after a 24 weeks treatment regimen of sofosbuvir plus velpatasvir with or without ribavirin combination and are eligible for pegylated interferon, will be treated with a combination of sofosbuvir, ledipasvir, ribavirin plus pegylated interferon

Drug: Sof+Dacla+R+Peg-IFN arm

Sof+Velpa+R arm

EXPERIMENTAL

Following group of participants will be treated with sofosbuvir, velpatasvir and ribavirin combination 1. who were treated earlier with 12 week treatment regimen of either sofosbuvir plus daclatasvir or sofosbuvir plus ledipasvir with or without ribavirin or 2. who were earlier treated with a 24 treatment regimen of either sofosbuvir plus daclatasvir or sofosbuvir plus ledipasvir with or without ribavirin and are not eligible for pegylated interferon

Drug: Sof+Velpa+R arm

Sof+Velpa+R+Peg-IFN arm

EXPERIMENTAL

Participants, who have relapsed after a 24 week treatment regimen of either sofosbuvir plus daclatasvir or sofosbuvir plus ledipasvir with or without ribavirin and are eligible for pegylated interferon will be treated with sofosbuvir, velpatasvir, ribavirin and pegylated interferon combination

Drug: Sof+Velpa+R+Peg-IFN arm

Interventions

Sof+Ledi+R arm DRUG

Fixed dose combination of sofosbuvir 400 mg plus ledipasvir 90 mg once daily plus ribavirin 1000 mg (body weight \<75 kg) or 1200 mg (body weight =\>75 kg) daily in two divided doses

Also known as: SLR

Sof+Ledi+R arm

Sof+Ledi+R+Peg-IFN arm DRUG

Fixed dose combination of sofosbuvir 400 mg plus ledipasvir 90 mg once daily plus ribavirin 1000 mg (body weight \<75 kg) or 1200 mg (body weight =\>75 kg) daily in two divided doses plus pegylated interferon alpha 2b @ 1.5 microgram/kg subcutaneously once in a week

Also known as: SLR+Peg

Sof+Ledi+R+Peg-IFN arm

Sof+Dacla+R arm DRUG

Sofosbuvir 400 mg once daily plus daclatasvir 100 mg once daily plus ribavirin 1000 mg (body weight \<75 kg) or 1200 mg (body weight =\>75 kg) daily in two divided doses

Also known as: SDR

Sof+Dacla+R arm

Sof+Dacla+R+Peg-IFN arm DRUG

Sofosbuvir 400 mg once daily plus daclatasvir 100 mg once daily plus ribavirin 1000 mg (body weight \<75 kg) or 1200 mg (body weight =\>75 kg) daily in two divided doses plus pegylated interferon alpha 2b @ 1.5 microgram/kg subcutaneously once in a week

Also known as: SDR+Peg

Sof+Dacla+R+Peg-IFN arm

Sof+Velpa+R arm DRUG

Fixed dose combination of sofosbuvir 400 mg plus velpatasvir 100 mg once daily plus ribavirin 1000 mg (body weight \<75 kg) or 1200 mg (body weight =\>75 kg) daily in two divided doses

Also known as: SVR

Sof+Velpa+R arm

Sof+Velpa+R+Peg-IFN arm DRUG

Fixed dose combination of sofosbuvir 400 mg plus velpatasvir 100 mg once daily plus ribavirin 1000 mg (body weight \<75 kg) or 1200 mg (body weight =\>75 kg) daily in two divided doses plus pegylated interferon alpha 2b @ 1.5 microgram/kg subcutaneously once in a week

Also known as: SVR+Peg

Sof+Velpa+R+Peg-IFN arm

Eligibility Criteria

• Age: 19 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• participants with chronic HCV infection and viremia, who have completed the DAA-based standard treatment and relapsed
• regardless of severity of liver disease, HCV genotype, nature or duration of DAAs,and whether treatment-naïve or previously treated with Peg-IFN/ribavirin

You may not qualify if:

• Participants with chronic kidney disease
• Post-organ transplant recipients
• Short life expectancy (\<1 year)
• Not willing to follow-up
• Individuals with immunocompromised states: HIV, immunosuppressive drugs, cancer chemotherapy, congenital hemolytic anemia

Sponsors & Collaborators

• Sanjay Gandhi Postgraduate Institute of Medical Sciences: lead
• Ram Manohar Lohia Institute of Medical Sciences, Lucknow: collaborator

Study Sites (2)

Sanjay Gandhi Postgraduate Institute of Medical Sciences

Lucknow, Uttar Pradesh, 226014, India

Location

RML Institute of Medical Sciences

Lucknow, Uttar Pradesh, India

Location

Related Publications (1)

• Goel A, Katiyar H, Mayank, Tiwari P, Rungta S, Verma A, Deep A, Sana A, Rai P, Aggarwal R. Hepatitis C Retreatment With First-Line Direct Acting Antiviral Drugs. J Clin Exp Hepatol. 2023 Sep-Oct;13(5):736-741. doi: 10.1016/j.jceh.2023.03.007. Epub 2023 Mar 24.

  PMID: 37693269 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Rakesh Aggarwal, DM

  Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Participants who relapsed to prior treatment with one or two DAA will be retreated with second course of DAA regimen and ribavirin with or without pegylated interferon. The duration of treatment will be 24 weeks. The drugs will be chosen based upon their prior exposure to DAA, liver disease severity and virus genotype.

Study Record Dates

• First Submitted: March 24, 2018
• First Posted: March 30, 2018
• Study Start: February 10, 2018
• Primary Completion: April 30, 2022
• Study Completion: April 30, 2022
• Last Updated: May 10, 2022

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

IN (2)