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Trial record 19 of 115 for:    "Viral Infectious Disease" | "Ledipasvir"

Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination +/- Ribavirin in Adolescents and Children With Chronic HCV-Infection

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ClinicalTrials.gov Identifier: NCT02249182
Recruitment Status : Completed
First Posted : September 25, 2014
Results First Posted : April 24, 2019
Last Update Posted : April 24, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:

The primary objective of the PK Lead-in Phase of the study is to evaluate the steady state pharmacokinetics (PK) and confirm the dose of ledipasvir/sofosbuvir (LDV/SOF) fixed dose combination (FDC) in hepatitis C virus (HCV)-infected pediatric participants. The PK Lead-in Phase will also evaluate the safety, tolerability, and antiviral activity of 10 days of dosing of LDV/SOF FDC in HCV-infected pediatric participants.

The Treatment Phase will be initiated by age cohort after confirmation of age-appropriate LDV/SOF FDC dosage levels. Participants from the PK Lead-in Phase will immediately rollover into the Treatment Phase with no interruption of study drug administration. The primary objective of the Treatment Phase is to evaluate the antiviral efficacy, safety, and tolerability of LDV/SOF FDC +/- ribavirin (RBV) for 12 or 24 weeks in pediatric participants with HCV.

During screening, participants will receive placebo to match LDV/SOF FDC to assess ability to swallow tablets.


Condition or disease Intervention/treatment Phase
Hepatitis C Virus Infection Drug: LDV/SOF Drug: RBV Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 226 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label, Multicenter, Multi-cohort Study to Investigate the Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination +/- Ribavirin in Adolescents and Children With Chronic HCV-Infection
Actual Study Start Date : November 5, 2014
Actual Primary Completion Date : June 15, 2018
Actual Study Completion Date : August 24, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 12 to < 18 Years Old

Participants between 12 to < 18 years of age weighing ≥ 45 kg will receive LDV/SOF FDC (90/400 mg tablet or 4 x 22.5 mg/100 mg tablets or 8 x 11.25/50 mg granules based on swallowability assessment during screening).

Treatment duration will be dependent on HCV genotype, prior treatment experience, cirrhosis status, and country of enrollment.

United Kingdom:

  • HCV genotypes (GT) 1, 4, 5, or 6 treatment-naive (TN) with or without cirrhosis = LDV/SOF 12 weeks
  • HCV GT 1, 4, 5, or 6 treatment-experienced (TE) without cirrhosis = LDV/SOF 12 weeks
  • HCV GT 1, 4, 5, or 6 TE with cirrhosis = LDV/SOF 24 weeks
  • HCV GT 3 TE with or without cirrhosis = LDV/SOF+RBV 24 weeks

United States/Australia/New Zealand:

  • HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks
  • HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks
  • HCV GT 1 TE with cirrhosis = LDV/SOF 24 weeks
  • HCV GT 4, 5, or 6 TE with cirrhosis = LDV/SOF 12 weeks
Drug: LDV/SOF
LDV/SOF FDC administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977

Drug: RBV
Ribavirin (RBV) oral solution or capsules will be administered orally in a divided daily dose based on weight
Other Name: REBETOL®

Experimental: 6 to < 12 Years Old

Participants between 6 to < 12 years of age weighing ≥ 17 kg and < 45 kg will receive LDV/SOF FDC (45/200 mg as 2 x 22.5/100 mg tablets or 4 x 11.25/50 mg granules based on swallowability assessment during screening).

Treatment duration will be dependent on HCV genotype, prior treatment experience, cirrhosis status, and country of enrollment.

United Kingdom:

  • HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks
  • HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks
  • HCV GT 1, 4, 5, or 6 TE with cirrhosis = LDV/SOF 24 weeks
  • HCV GT 3 TE with or without cirrhosis = LDV/SOF+RBV 24 weeks

United States/Australia/New Zealand:

  • HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks
  • HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks
  • HCV GT 1 TE with cirrhosis = LDV/SOF 24 weeks
  • HCV GT 4, 5, or 6 TE with cirrhosis = LDV/SOF 12 weeks
Drug: LDV/SOF
LDV/SOF FDC administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977

Drug: RBV
Ribavirin (RBV) oral solution or capsules will be administered orally in a divided daily dose based on weight
Other Name: REBETOL®

Experimental: 3 to < 6 Years Old

Participants between 3 to < 6 years of age weighing ≥ 17 kg will receive LDV/SOF FDC (45/200 mg granules as 4 x 11.25/50 mg packets) and participants weighing < 17 kg will receive LDV/SOF FDC (33.75/150 mg oral granules as 3 x 11.25/50 mg packets).

Treatment duration will be dependent on HCV genotype, prior treatment experience, cirrhosis status, and country of enrollment.

United Kingdom:

  • HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks
  • HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks
  • HCV GT 1, 4, 5, or 6 TE with cirrhosis = LDV/SOF 24 weeks
  • HCV GT 3 TE with or without cirrhosis = LDV/SOF+RBV 24 weeks

United States/Australia/New Zealand:

  • HCV GT 1, 4, 5, or 6 TN with or without cirrhosis = LDV/SOF 12 weeks
  • HCV GT 1, 4, 5, or 6 TE without cirrhosis = LDV/SOF 12 weeks
  • HCV GT 1 TE with cirrhosis = LDV/SOF 24 weeks
  • HCV GT 4, 5, or 6 TE with cirrhosis = LDV/SOF 12 weeks
Drug: LDV/SOF
LDV/SOF FDC administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977

Drug: RBV
Ribavirin (RBV) oral solution or capsules will be administered orally in a divided daily dose based on weight
Other Name: REBETOL®




Primary Outcome Measures :
  1. For Participants in the PK Lead-in Phase, Pharmacokinetic (PK) Parameter: AUCtau of GS-331007 (Metabolite of SOF), LDV, and SOF [ Time Frame: Cohorts 1 and 2 (6 to < 18 years of age): predose, 0.5, 1, 2, 3, 4, 5, 8, and 12 hours postdose on Day 10; Cohort 3 (3 to < 6 years of age): predose, 0.5, 2, 4, 8, and 12 hours postdose on Day 10 ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

  2. Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase or the Treatment Phase [ Time Frame: Up to 24 weeks ]

Secondary Outcome Measures :
  1. For Participants in the PK Lead-in Phase, Change From Baseline in HCV RNA [ Time Frame: Baseline; Weeks 1, 2, 4, 8, and 12 ]
  2. Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event During the PK Lead-in Phase [ Time Frame: Up to Day 10 ]
  3. For the Treatment Phase, Percentage of Participants With Sustained Virologic Response (SVR) at 4 Weeks After Discontinuation of Therapy (SVR4) [ Time Frame: Posttreatment Week 4 ]
    SVR4 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 4 weeks after stopping study treatment.

  4. For the Treatment Phase, Percentage of Participants With SVR at 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: Posttreatment Week 12 ]
    SVR12 was defined as HCV RNA < LLOQ at 12 weeks after stopping study treatment.

  5. For the Treatment Phase, Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) [ Time Frame: Posttreatment Week 24 ]
    SVR24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment.

  6. For the Treatment Phase, Percentage of Participants Experiencing Viral Breakthrough [ Time Frame: Up to 24 weeks ]
    Viral breakthrough was defined as having confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment.

  7. For the Treatment Phase, Percentage of Participants Experiencing Viral Relapse [ Time Frame: Up to Posttreatment Week 24 ]
    Viral relapse was defined as having confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.

  8. For the Treatment Phase, Change From Baseline in HCV RNA [ Time Frame: Baseline; Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only) ]
  9. For the Treatment Phase, Percentage of Participants With HCV RNA < LLOQ While On Treatment [ Time Frame: Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only) ]
  10. For the Treatment Phase, Percentage of Participants With Alanine Aminotransferase (ALT) Normalization [ Time Frame: Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only), and Posttreatment Week 4 ]
    ALT normalization was defined as ALT > the upper limit of normal (ULN) at baseline and ALT ≤ ULN at each visit.

  11. For the Treatment Phase, Change From Baseline in Height [ Time Frame: Baseline; Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only), and Posttreatment Weeks 4, 12, and 24 ]
  12. For the Treatment Phase, Change From Baseline in Weight [ Time Frame: Baseline; Weeks 1, 2, 4, 8, 12, 16 (24 Week groups only), 20 (24 Week groups only), and 24 (24 Week groups only), and Posttreatment Weeks 4, 12, and 24 ]
  13. For the Treatment Phase, Number of Male Participants With a Change From Baseline in Tanner Stage for Pubic Hair [ Time Frame: Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24 ]
    Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics). Any shifts (increase or decrease) in Tanner Stage from Baseline were analyzed and presented.

  14. For the Treatment Phase, Number of Male Participants With a Change From Baseline in Tanner Stage for Genitalia Development [ Time Frame: Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24 ]
    Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics). Any shifts (increase or decrease) in Tanner Stage from Baseline were analyzed and presented.

  15. For the Treatment Phase, Number of Female Participants With a Change From Baseline in Tanner Stage for Pubic Hair [ Time Frame: Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24 ]
    Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics). Any shifts (increase or decrease) in Tanner Stage from Baseline were analyzed and presented.

  16. For the Treatment Phase, Number of Female Participants With a Change From Baseline in Tanner Stage for Breast Development [ Time Frame: Baseline; End of Treatment (either Week 12 or 24), Posttreatment Week 12, and Posttreatment Week 24 ]
    Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics). Any shifts (increase or decrease) in Tanner Stage from Baseline were analyzed and presented.

  17. Acceptability of LDV/SOF Tablets as Measured by the Percentage of Participants Able/Unable to Swallow Placebo Tablet at Day 1 [ Time Frame: Day 1 ]
    Participants who were able/unable to swallow placebo tablets were assessed. Participants 12 to < 18 years old were first asked to perform the swallowability assessment using the 90/400 mg placebo tablet. If they were unable to swallow this, they were then asked to perform the swallowability assessment with 22.5/100 mg placebo tablets. Participants 6 to < 12 years old were to be assessed with the 22.5/100 mg placebo tablets. However, 8 participants were mistakenly assessed using the 90/400 mg placebo tablet.

  18. Acceptability of LDV/SOF Granules as Measured by Palatability at Day 1 [ Time Frame: Day 1 ]
    Participants who were dosed with granules were asked if they tasted the study drug. If they tasted it, then they were asked to provide a number from 0 to 100 to rate the taste of the study drug, with higher scores indicating better taste. Data was then summarized as percentage of participants choosing the following palatability categories: 1) Did not taste the study drug, 2) Tasted drug with score > 60 to 100, 3) Tasted drug with score 40 to 60, and 4) Tasted drug with score of 0 to < 40.



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:   3 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Consent of parent or legal guardian required
  • Chronic HCV infection
  • Screening laboratory values within defined thresholds

Key Exclusion Criteria:

  • History of clinically significant illness or any other medical disorder that may interfere with individual's treatment, assessment or compliance with the protocol.
  • Co-infection with HIV, acute hepatitis A virus, or hepatitis B virus
  • Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage)
  • Pregnant or nursing females
  • Known hypersensitivity to study medication
  • Use of any prohibited concomitant medications as within 28 days of the Day 1 visit

Note: Other protocol defined Inclusion/Exclusion criteria may apply.


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): NCT02249182


  Show 31 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
  Study Documents (Full-Text)

Documents provided by Gilead Sciences:
Study Protocol: Original  [PDF] July 10, 2014
Study Protocol: Amendment 1  [PDF] October 8, 2014
Study Protocol: Amendment 2  [PDF] December 8, 2014
Study Protocol: Amendment 3  [PDF] May 28, 2015
Study Protocol: Amendment 4  [PDF] March 15, 2016
Study Protocol: Amendment 5  [PDF] November 4, 2016
Study Protocol: Amendment 6  [PDF] June 8, 2017
Statistical Analysis Plan  [PDF] July 10, 2018


Publications of Results:
Kirby B, German P, Kanwar B, Ni L, Lakatos I, Ling J, Mathias A. Pharmacokinetics of Once-Daily Sofosbuvir and Ledipasvir/Sofosbuvir in HCV-Infected Adolescents. Hepatology 2015;62 (S1): 1040A-1041A
Garrison KL, Mathias A, Kersey K, Kanwar B, Ni L, Jain A, et al. Pharmacokinetics of Once-Daily Sofosbuvir and Ledipasvir/Sofosbuvir in HCV-Infected Pediatrics Aged 6 to < 12 Years Old. Hepatology 2016;64 (S1): 436A
Schwarz K, Murray KF, Rosenthal P, Bansal S, Lin CH, Ni L, et al. High Rates of SVR12 in Adolescents Treated with the Combination of Ledipasvir/Sofosbuvir. J Hepatol 2016; 64 (2): S184-S185
K.F. Murray, W. Balistreri, S. Bansal, S. Whitworth, H. Evans, R.P. Gonzalez-Peralta, et al. Ledipasvir/sofosbuvir ± ribavirin for 12 or 24 weeks is safe and effective in children 6-11 years old with chronic hepatitis C infection. J Hepatol 2017;66: S33-S62
Begley R, Meng A, Massetto B, Shao J, Ling J, and Mathias A. Pharmacokinetics of Once Daily Sofosbuvir or Ledipasvir/Sofosbuvir in HCV-Infected Pediatrics Aged 3 to <6 Years Old. Hepatology 2018;68 (S1): 582A.
Schwarz KB, Rosenthal P, Murray KF, Honegger JR, Hardikar W, Hague R, et al. Ledipasvir/Sofosbuvir for 12 Weeks Is Safe and Effective in Children 3 to <6 Years Old with Chronic Hepatitis C Virus Infection. Hepatology 2018;68 (S1): 116A-117A.

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02249182     History of Changes
Other Study ID Numbers: GS-US-337-1116
2014-003578-17 ( EudraCT Number )
First Posted: September 25, 2014    Key Record Dates
Results First Posted: April 24, 2019
Last Update Posted: April 24, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at www.gilead.com/about/ethics-and-code-of-conduct/policies.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: 18 months after study completion
Access Criteria: A secured external environment with username, password, and RSA code.
URL: https://www.gilead.com/about/ethics-and-code-of-conduct/policies

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Virus Diseases
RNA Virus Infections
Ledipasvir
Ledipasvir, sofosbuvir drug combination
Infection
Communicable Diseases
Hepatitis C
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Flaviviridae Infections
Ribavirin
Sofosbuvir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents