Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT03483987 |
| Other study ID # |
2017-202-IP-100 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 10, 2018 |
| Est. completion date |
April 30, 2022 |
Study information
| Verified date |
April 2021 |
| Source |
Sanjay Gandhi Postgraduate Institute of Medical Sciences |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
