Re-treatment of HCV Following DAA Failure

  • STATUS
    Recruiting
  • End date
    Dec 31, 2022
  • participants needed
    50
  • sponsor
    Sanjay Gandhi Postgraduate Institute of Medical Sciences
Updated on 11 April 2021
ribavirin
liver disease
cirrhosis
hcv genotype
sofosbuvir
daclatasvir
ledipasvir
velpatasvir

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.

Description

-Introduction Oral drugs, termed collectively as 'Direct-acting anti-viral agents' (DAAs), are the standard-of-care for HCV treatment. In India, four DAAs, namely sofosbuvir (SOF), daclatasvir (DCV), ledipasvir (LDV) and velpatasvir (VEL), are marketed. Initially, people were treated using SOF in combination with ribavirin with or without pegylated-interferon (Peg-IFN). Thereafter, HCV treatment was switched to use of two DAAs with or without ribavirin and discontinuation of Peg-IFN. All these combinations of DAAs have obtained excellent rates of cure - defined as undetectable HCV RNA at 12 weeks after stopping DAA-based HCV, also referred to as sustained virological response at week 12 (SVR12).

Though DAAs-based anti-HCV treatment has shown generally excellent results, globally some patients fail to achieve SVR12. The rate of such failure is higher in patients with advanced liver disease and HCV genotype 3 infections. In India, genotype 3 is the most prevalent HCV genotype (~65%), followed by genotype 1 (~30%).

Data on management of the people who relapse after DAA treatment are extremely limited, and no guidelines exist regarding retreatment options for them. Hence, physician need to re-treat such people with the best combination available in a given situation.

  • Objective To study the re-treatment response in people with chronic HCV infection and relapsed to prior DAA based treatment
  • Rationale for the proposed treatment regimens

Overall, investigators attempted to tried to combine drugs to give the best chance of virus clearance to those with prior treatment failure by following the following principles, as have emerged from the experience worldwide:

  1. Prolongation of treatment duration to 24 weeks if previous treatment was for 12 weeks
  2. Addition of pegylated interferon (previous standard of care for HCV, and which acts by a different mechanism) if person has previously failed 24 weeks of dual-DAA treatment
  3. Addition of ribavirin, if it appears that the participant can tolerate this drug.
  4. Use of sofosbuvir (a NS5b inhibitor) as the backbone of re-treatment, since drug resistance to this drug is the least common
  5. Use of a pangenotypic drug (velpatasvir) if the previous treatment was with a genotype-specific NS5a inhibitor (daclatasvir or ledipasvir)
  6. Use of genotype-specific drug (daclatasvir or ledipasvir) if the previous treatment was with a pan-genotypic NS5a inhibitor (velpatasvir)
    • Methods Relevant clinical, laboratory and treatment details will be recorded in pre-defined data collection form, used for monitoring patients with HCV infection as part of their clinical care. Treatment outcome will be categorized as successful (SVR12), treatment failure (any detectable HCV RNA at the end of pre-defined 12-24 weeks treatment duration) or relapse (HCV RNA negative at the end of treatment, but positive at 12 weeks after stopping treatment). The data will be analyzed for the entire group and for specific subgroups, such as: (i) those without cirrhosis; (ii) those with compensated cirrhosis; (iii) those with decompensated cirrhosis
    • Blood specimen collection If possible, a 5 ml blood specimen will be collected before starting anti-HCV retreatment from all the participants. If the HCV retreatment also fails, then a repeat 5 ml blood specimen will be collected for virological studies.
    • Follow-up plan During anti-HCV treatment: HCV RNA will be tested at 4-week intervals starting from week 4 till RNA reports are negative, and then at the end of treatment and 12 weeks after stopping treatment.
    • Sample size Considering usual clinical load, investigators expect to treat around 1000-1200 DAA treatment naive people with chronic HCV infection between during the study period. considering a 5% relapse rate, HCV relapse is expected in about 50 people.

Details
Condition Chronic viral hepatitis C
Treatment Sof+Ledi+R arm, Sof+Ledi+R+Peg-IFN arm, Sof+Dacla+R arm, Sof+Dacla+R+Peg-IFN arm, Sof+Velpa+R arm, Sof+Velpa+R+Peg-IFN arm
Clinical Study IdentifierNCT03483987
SponsorSanjay Gandhi Postgraduate Institute of Medical Sciences
Last Modified on11 April 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age between 19 yrs and 65 yrs?
Gender: Male or Female
Do you have Chronic viral hepatitis C?
Do you have any of these conditions: Do you have Chronic viral hepatitis C??
Do you have any of these conditions: Do you have Chronic viral hepatitis C??
Do you have any of these conditions: Do you have Chronic viral hepatitis C??
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-nave or previously treated with Peg-IFN/ribavirin

Exclusion Criteria

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
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

Phone Email

0/250
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note