Study to Investigate the Safety and Efficacy of Sofosbuvir/Velpatasvir in Adolescents and Children With Chronic HCV Infection
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| ClinicalTrials.gov Identifier: NCT03022981 |
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Recruitment Status :
Completed
First Posted : January 18, 2017
Results First Posted : October 8, 2020
Last Update Posted : October 8, 2020
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Sponsor:
Gilead Sciences
Information provided by (Responsible Party):
Gilead Sciences
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Brief Summary:
This study will have 2 parts: Pharmacokinetics (PK) Lead-in Phase and the Treatment Phase.
The primary objective of the PK Lead-in Phase is to evaluate the steady state PK and confirm the dose of sofosbuvir/velpatasvir (SOF/VEL) fixed-dose combination (FDC) in pediatric participants with chronic hepatitis C virus (HCV) infection.
The primary objective of the Treatment Phase is to evaluate the safety and tolerability of SOF/VEL for 12 weeks in pediatric participants with chronic HCV.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hepatitis C Virus Infection | Drug: SOF/VEL | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 216 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 Sofosbuvir/Velpatasvir in Adolescents and Children With Chronic HCV Infection |
| Actual Study Start Date : | January 26, 2017 |
| Actual Primary Completion Date : | November 19, 2019 |
| Actual Study Completion Date : | February 26, 2020 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Sofosbuvir
| Arm | Intervention/treatment |
|---|---|
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Experimental: 12 to < 18 Years Old
PK Lead-in Phase: Sofosbuvir/Velpatasvir (SOF/VEL) 400/100 mg once daily for 7 days. Participants who complete the PK lead-in phase, continue into the treatment phase with no interruption of study drug administration and additional participants will be enrolled into the treatment phase once the appropriateness of the dose is confirmed by PK results from the PK lead-in phase. Treatment Phase: SOF/VEL 400/100 mg once daily for 12 weeks. |
Drug: SOF/VEL
SOF/VEL fixed-dose combination (FDC) 400/100 mg tablets or SOF/VEL FDC 200/50 mg tablets (based on swallowability assessment)
Other Names:
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Experimental: 6 to < 12 Years Old
PK Lead-in Phase: SOF/VEL 200/50 mg once daily for 7 days. Participants who complete the PK lead-in phase, continue into the treatment phase with no interruption of study drug administration and additional participants will be enrolled into the treatment phase once the appropriateness of the dose is confirmed by PK results from the PK lead-in phase. Treatment Phase: SOF/VEL 200/50 mg once daily for 12 weeks. |
Drug: SOF/VEL
SOF/VEL fixed-dose combination (FDC) 400/100 mg tablets or SOF/VEL FDC 200/50 mg tablets (based on swallowability assessment)
Other Names:
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Experimental: 3 to < 6 Years Old
PK Lead-in Phase: SOF/VEL 200/50 mg once daily for 7 days for participants who weigh ≥ 17 kg. SOF/VEL 150/37.5 mg once daily for 7 days for participants who weigh < 17 kg. Participants who complete the PK lead-in phase, continue into the treatment phase with no interruption of study drug administration and additional participants will be enrolled into the treatment phase once the appropriateness of the dose is confirmed by PK results from the PK lead-in phase. Treatment Phase: SOF/VEL 200/50 mg once daily for 12 weeks for participants who weigh ≥ 17 kg. SOF/VEL 150/37.5 mg once daily for 12 weeks for participants who weigh < 17 kg. |
Drug: SOF/VEL
SOF/VEL FDC 200/50 mg oral granules
Other Names:
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Primary Outcome Measures :
- PK Lead-in Phase: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Velpatasvir (VEL) [ Time Frame: Day 7: 0 (predose), 0.5, 1, 2, 3, 4, 6 (Cohorts 1 and 2 only), 8, and 12 hours postdose ]AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).
- PK Lead-in Phase: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Sofosbuvir (SOF) [ Time Frame: Day 7: 0 (predose), 0.5, 1, 2, 3, 4, 6 (Cohorts 1 and 2 only), 8, and 12 hours postdose ]AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).
- PK Lead-in Phase: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of GS-331007 (Metabolite of SOF) [ Time Frame: Day 7: 0 (predose), 0.5, 1, 2, 3, 4, 6 (Cohorts 1 and 2 only), 8, and 12 hours postdose ]AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
- Treatment Phase: Percentage of Participants Who Discontinued Study Drug Due to Any Treatment-Emergent Adverse Event (TEAE) [ Time Frame: From first dose through last dose of the study drug (Up to 12 weeks) plus 30 days ]An AE is any untoward medical occurrence in a clinical study participant administered a medicinal product, which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as 1 or both of the following: Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug and/or Any AEs leading to premature discontinuation of study drug.
Secondary Outcome Measures :
- PK Lead-in Phase: Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 7 [ Time Frame: Baseline; Day 7 ]
- PK Lead-in Phase: Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event (AE) [ Time Frame: First dose date up to Day 7 ]An AE is any untoward medical occurrence in a clinical study participant administered a medicinal product, which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
- Treatment Phase: Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: Posttreatment Week 12 ]SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
- Treatment Phase: Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) [ Time Frame: Posttreatment Week 4 ]SVR4 was defined as HCV RNA < LLOQ (ie, 15 IU/mL) at 4 weeks after stopping study treatment.
- Treatment Phase: Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) [ Time Frame: Posttreatment Week 24 ]SVR 24 was defined as HCV RNA < LLOQ (ie, 15 IU/mL) at 24 weeks after stopping study treatment.
- Treatment Phase: Percentage of Participants With Virologic Failure [ Time Frame: Up to Posttreatment Week 24 ]Virologic failure was defined as: On-treatment virologic failure - Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment); Virologic relapse: Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.
- Treatment Phase: Percentage of Participants With HCV RNA < LLOQ On Treatment [ Time Frame: Weeks 1, 4, 8, and 12 ]Percentage of participants with HCV RNA < LLOQ while on treatment by analysis visit.
- Treatment Phase: Percentage of Participants Who Develop Viral Resistance to SOF and/or VEL During Treatment and After Discontinuation of Treatment [ Time Frame: First dose date up to Posttreatment Week 24 ]Drug-resistant substitutions were analyzed as part of the Virology Study. Plasma samples were collected and stored for potential HCV sequencing. Impact on the treatment outcomes of SVR12 and SVR24 were observed during the study. Baseline deep sequencing of the HCV nonstructural protein (NS)5A and NS5B genes was performed for all participants at the first time point after virologic failure if the plasma or serum sample was available. Pretreatment full-length NS5A deep sequencing data were obtained at a 15% assay cutoff for the Resistance Analysis Population which covered all NS5A and NS5B nucleoside inhibitor (NI) resistance-associated variants (RAVs).
- Treatment Phase: Change From Baseline in HCV RNA at Weeks 1, 4, 8, and 12 [ Time Frame: Baseline; Weeks 1, 4, 8, and 12 ]
- Treatment Phase: Quality of Life (QoL) and Neuropsychiatric Assessments as Measured by PedsQL™ Pediatric QoL Survey [ Time Frame: Baseline; Week 12, End of Treatment (EOT), Posttreatment/Follow-up (FU) Week-12 (FU-12), and FU Week-24 (FU-24) ]To evaluate the effect of treatment with SOF/VEL on general and disease-specific health-related QoL, the PedsQL™ Pediatric QoL Inventory V4.0 Short Form (SF15) was completed at Day 1, end of treatment, early termination (if applicable), and posttreatment Weeks 12 and 24. The SF15 questionnaire represented 4 domains: physical, emotional, social, and school functioning, with the emotional, social, and school functioning domains representing the psychosocial health summary. Neuropsychiatric assessment was conducted using the PedsQL™ Pediatric QoL Inventory V4.0 SF15 psychosocial domain-related scores. Items were calculated and transformed into an overall score with a range of 0 to 100 points, with more points indicating better QoL.
- Treatment Phase: Change From Baseline in Growth and Development as Measured by Height Percentiles [ Time Frame: Baseline; Weeks 1, 4, 8, 12, Follow-up (FU) Week 4 (FU-4), FU-12, and FU-24 ]An age- and sex-specific percentile was derived for each weight, height, and body mass index (BMI) measurement according to the statistical analysis system (SAS) program available on the Centers for Disease Control and Prevention (CDC) website using the year 2000 growth charts.
- Treatment Phase: Change From Baseline in Growth and Development as Measured by Weight Percentiles [ Time Frame: Baseline; Weeks 1, 4, 8, 12, FU-4, FU-12, and FU-24 ]An age- and sex-specific percentile was derived for each weight, height, and BMI measurement according to the SAS program available on the CDC website using the year 2000 growth charts.
- Treatment Phase: Changes in Growth and Development as Measured by Tanner Stage Assessment From Baseline [ Time Frame: Baseline; EOT, FU-12 and FU-24 ]Tanner Pubertal Staging was assessed for pubic hair growth and genitalia development (males) and for pubic hair growth and breast development (females) in stages 1 to 5. Tanner stages were used to evaluate the onset and progression of pubertal changes from stage 1 (pre-pubertal) to stage 5 (adult). If a participant had reached Tanner stage 5, no further Tanner pubertal stage assessments were to be completed. Pubic hair growth: Tanner stages (1: No hair, 2: Downy hair, 3: More coarse and curly hair, 4: Adult-like hair quality; 5: Hair extends to the medial surface of the thighs); Breast development: Tanner stages (1: No glandular tissue, 2: Breast bud forms,3: More elevated, outside areola, 4: Increased breast size,5: Final adult-size breasts); Genitalia development: Tanner stages (1: Testes, scrotum, and penis about same size, 2: Enlargement of scrotum, testes and penis, 3: Enlargement of penis, 4: Penis size enlargement, 5: Genitalia adult in size and shape).
- Treatment Phase: Growth and Development as Measured by Parental Height [ Time Frame: Day 1 ]Mid-parental height was calculated as the average of the biological father's and mother's heights. For boys, the sex-adjusted mid-parental height was calculated by adding 2.5 inches or 6.5 cm to the mean of the parents' heights. For girls, 2.5 inches or 6.5 cm was subtracted from the mean of the parents' heights.
- Treatment Phase: Change From Baseline in Growth and Development as Measured by Bone Age [ Time Frame: Baseline; FU-24 ]Bone age was determined based on x-ray of the left wrist, hand, and fingers. Baseline value is the last available value on or prior to first dose date of study drug.
- Treatment Phase: Swallowability of SOF/VEL as Assessed by the Participant's Ability to Swallow SOF/VEL Placebo Tablets at Baseline [ Time Frame: Baseline ]A SOF/VEL FDC swallowability assessment was performed using placebo tablets at baseline.
- Treatment Phase: Number of Participants With Acceptability of SOF/VEL as Measured by a Questionnaire to Assess Acceptability, Including Palatability at Day 1 [ Time Frame: Day 1 ]Acceptability was assessed by numeric response marked on line between numbers 0 - 100. Higher scores indicate better acceptability and/or palatability.
- Treatment Phase: Number of Participants With Acceptability of SOF/VEL as Measured by a Questionnaire to Assess Acceptability, Including Palatability at Week 12 [ Time Frame: Week 12 ]Acceptability was assessed by numeric response marked on line between numbers 0 - 100. Higher scores indicate better acceptability and/or palatability.
Information from the National Library of Medicine
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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:
- Chronic HCV-infected, treatment-naive and treatment-experienced adolescent and pediatric individuals aged 3 to < 18 as determined at Day 1.
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): NCT03022981
Locations
Show 27 study locations
Sponsors and Collaborators
Gilead Sciences
Investigators
| Study Director: | Gilead Study Director | Gilead Sciences |
Study Documents (Full-Text)
Documents provided by Gilead Sciences:
Documents provided by Gilead Sciences:
Study Protocol [PDF] June 15, 2018
Statistical Analysis Plan [PDF] April 20, 2020
Publications of Results:
Jonas MM, Romero R, Sokal EM, Rosenthal P, Verucchi G, Lin CH, et al. The Safety and Efficacy of Sofosbuvir/Velpatasvir in Pediatric Patients 6 to < 18 years old with Chronic Hepatitis C Infection [Abstract]. AASLD; 2019 08-12 November; Boston, Massachusetts.
| Responsible Party: | Gilead Sciences |
| ClinicalTrials.gov Identifier: | NCT03022981 |
| Other Study ID Numbers: |
GS-US-342-1143 2016-002446-23 ( EudraCT Number ) |
| First Posted: | January 18, 2017 Key Record Dates |
| Results First Posted: | October 8, 2020 |
| Last Update Posted: | October 8, 2020 |
| Last Verified: | October 2020 |
| 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 https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy |
| 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/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy |
| 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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Infections Communicable Diseases Hepatitis C Disease Attributes Pathologic Processes Hepatitis Liver Diseases Digestive System Diseases Blood-Borne Infections |
Hepatitis, Viral, Human Virus Diseases Flaviviridae Infections RNA Virus Infections Sofosbuvir Sofosbuvir-velpatasvir drug combination Velpatasvir Antiviral Agents Anti-Infective Agents |