Re-treatment of HCV Following DAA Failure

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

Interventions

DRUG

Sof+Ledi+R arm

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

DRUG

Sof+Ledi+R+Peg-IFN arm

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

DRUG

Sof+Dacla+R arm

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

DRUG

Sof+Dacla+R+Peg-IFN arm

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

DRUG

Sof+Velpa+R arm

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

DRUG

Sof+Velpa+R+Peg-IFN arm

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

Sponsors & Collaborators

• Ram Manohar Lohia Institute of Medical Sciences, Lucknow

  collaborator UNKNOWN

• Sanjay Gandhi Postgraduate Institute of Medical Sciences

  lead OTHER_GOV

Principal Investigators

• Rakesh Aggarwal, DM · Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

19 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-02-10

Primary Completion

2022-04-30

Completion

2022-04-30

Countries

• India

Study Locations