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Trial record 63 of 115 for:    "Viral Infectious Disease" | "Ledipasvir"

Re-treatment of HCV Following DAA Failure

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ClinicalTrials.gov Identifier: NCT03483987
Recruitment Status : Recruiting
First Posted : March 30, 2018
Last Update Posted : September 24, 2019
Sponsor:
Collaborator:
Ram Manohar Lohia Institute of Medical Sciences, Lucknow
Information provided by (Responsible Party):
Sanjay Gandhi Postgraduate Institute of Medical Sciences

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.


Condition or disease Intervention/treatment Phase
Chronic Hepatitis C Drug: Sof+Ledi+R arm Drug: Sof+Ledi+R+Peg-IFN arm Drug: Sof+Dacla+R arm Drug: Sof+Dacla+R+Peg-IFN arm Drug: Sof+Velpa+R arm Drug: Sof+Velpa+R+Peg-IFN arm Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Re-treatment of Chronic Hepatitis C Virus Infection Among Non-responders or Those Who Relapsed to Treatment With Regimens Based on Direct-acting Antiviral Drugs
Actual Study Start Date : February 10, 2018
Estimated Primary Completion Date : January 9, 2021
Estimated Study Completion Date : October 9, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sof+Ledi+R arm

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
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
Other Name: SLR

Experimental: Sof+Ledi+R+Peg-IFN arm
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
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
Other Name: SLR+Peg

Experimental: Sof+Dacla+R arm

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
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
Other Name: SDR

Experimental: Sof+Dacla+R+Peg-IFN arm
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
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
Other Name: SDR+Peg

Experimental: Sof+Velpa+R arm

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
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
Other Name: SVR

Experimental: Sof+Velpa+R+Peg-IFN arm
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
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
Other Name: SVR+Peg




Primary Outcome Measures :
  1. SVR12 [ Time Frame: - 12 weeks after stopping 24 weeks of DAA based treatment ]
    Proportion of participants with undetectable HCV RNA at 12 weeks after stopping DAA-based HCV re-treatment



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   19 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03483987


Contacts
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Contact: Rakesh Aggarwal, DM +91-522249 ext 4431 aggarwal.ra@gmail.com
Contact: Amit Goel, DM +91-522249 ext 5548 agoel.ag@gmail.com

Locations
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India
Sanjay Gandhi Postgraduate Institute of Medical Sciences Recruiting
Lucknow, UP, India, 226014
Contact: Amit Goel, DM    9936275741      
RML Institute of Medical Sciences Recruiting
Lucknow, Uttar Pradesh, India
Contact: Amit Goel    +91-522249 ext 5548    agoel.ag@gmail.com   
Sponsors and Collaborators
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Ram Manohar Lohia Institute of Medical Sciences, Lucknow
Investigators
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Principal Investigator: Rakesh Aggarwal, DM Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGI)

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Responsible Party: Sanjay Gandhi Postgraduate Institute of Medical Sciences
ClinicalTrials.gov Identifier: NCT03483987     History of Changes
Other Study ID Numbers: 2017-202-IP-100
First Posted: March 30, 2018    Key Record Dates
Last Update Posted: September 24, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Presently, we have no plan to share data with other researchers

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sanjay Gandhi Postgraduate Institute of Medical Sciences:
Hepatitis c virus
Direct acting antiviral drugs
Virological relapse
Additional relevant MeSH terms:
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Virus Diseases
RNA Virus Infections
Ledipasvir
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
Flaviviridae Infections
Interferons
Ribavirin
Antiviral Agents
Sofosbuvir
Velpatasvir
Antineoplastic Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action