Study to Investigate the Safety and Efficacy of Sofosbuvir/Velpatasvir in Adolescents and Children With Chronic HCV Infection

Hepatitis C Virus Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03022981
• Other study ID #: GS-US-342-1143
• Secondary ID: 2016-002446-23
• Status: Completed
• Phase: Phase 2
• Start date: January 26, 2017
• Est. completion date: February 26, 2020

Study information

• Verified date: October 2020
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 216
• Est. completion date: February 26, 2020
• Est. primary completion date: November 19, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Hepatitis C
• Hepatitis C Virus Infection
• Infection

Intervention

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)
• SOF/VEL
SOF/VEL FDC 200/50 mg oral granules

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint Luc	Brussels
Italy	Azienda Ospedaliero-Universitaria di Bologna - Policlinico S. Orsola - Malpighi	Bologna
Italy	Azienda Ospedaliera Universitaria Meyer	Firenze
Italy	Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo
United Kingdom	The Leeds Teaching Hospitals NHS Trust	Leeds	England
United Kingdom	King's College Hospital NHS Trust	London	England
United States	Emory Children's Center	Atlanta	Georgia
United States	Children's Hospital of Colorado	Aurora	Colorado
United States	Johns Hopkins University (JHU) - The Johns Hopkins Hospital (JHH)	Baltimore	Maryland
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Nationwide Children's Hospital- The Ohio State University (OSU)	Columbus	Ohio
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	University of Florida Shands Medical	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Kosair Charities Pediatric Clinical Research Unit	Louisville	Kentucky
United States	Monroe Carell Jr. Children's Hospital at Vanderbilt	Nashville	Tennessee
United States	Mount Sinai Medical Center	New York	New York
United States	Children's Hospital & Medical Center	Omaha	Nebraska
United States	Florida Gastroenterology Care for Children	Orlando	Florida
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	University of California, San Francisco	San Francisco	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Belgium,  Italy,  United Kingdom, 

References & Publications (1)

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, Massachuse

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PK Lead-in Phase: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Velpatasvir (VEL)	AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).	Day 7: 0 (predose), 0.5, 1, 2, 3, 4, 6 (Cohorts 1 and 2 only), 8, and 12 hours postdose
Primary	PK Lead-in Phase: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Sofosbuvir (SOF)	AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval).	Day 7: 0 (predose), 0.5, 1, 2, 3, 4, 6 (Cohorts 1 and 2 only), 8, and 12 hours postdose
Primary	PK Lead-in Phase: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of GS-331007 (Metabolite of SOF)	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).	Day 7: 0 (predose), 0.5, 1, 2, 3, 4, 6 (Cohorts 1 and 2 only), 8, and 12 hours postdose
Primary	Treatment Phase: Percentage of Participants Who Discontinued Study Drug Due to Any Treatment-Emergent Adverse Event (TEAE)	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.	From first dose through last dose of the study drug (Up to 12 weeks) plus 30 days
Secondary	PK Lead-in Phase: Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Day 7		Baseline; Day 7
Secondary	PK Lead-in Phase: Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event (AE)	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.	First dose date up to Day 7
Secondary	Treatment Phase: Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12)	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.	Posttreatment Week 12
Secondary	Treatment Phase: Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)	SVR4 was defined as HCV RNA < LLOQ (ie, 15 IU/mL) at 4 weeks after stopping study treatment.	Posttreatment Week 4
Secondary	Treatment Phase: Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)	SVR 24 was defined as HCV RNA < LLOQ (ie, 15 IU/mL) at 24 weeks after stopping study treatment.	Posttreatment Week 24
Secondary	Treatment Phase: Percentage of Participants With Virologic Failure	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.	Up to Posttreatment Week 24
Secondary	Treatment Phase: Percentage of Participants With HCV RNA < LLOQ On Treatment	Percentage of participants with HCV RNA < LLOQ while on treatment by analysis visit.	Weeks 1, 4, 8, and 12
Secondary	Treatment Phase: Percentage of Participants Who Develop Viral Resistance to SOF and/or VEL During Treatment and After Discontinuation of Treatment	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).	First dose date up to Posttreatment Week 24
Secondary	Treatment Phase: Change From Baseline in HCV RNA at Weeks 1, 4, 8, and 12		Baseline; Weeks 1, 4, 8, and 12
Secondary	Treatment Phase: Quality of Life (QoL) and Neuropsychiatric Assessments as Measured by PedsQL™ Pediatric QoL Survey	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.	Baseline; Week 12, End of Treatment (EOT), Posttreatment/Follow-up (FU) Week-12 (FU-12), and FU Week-24 (FU-24)
Secondary	Treatment Phase: Change From Baseline in Growth and Development as Measured by Height Percentiles	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.	Baseline; Weeks 1, 4, 8, 12, Follow-up (FU) Week 4 (FU-4), FU-12, and FU-24
Secondary	Treatment Phase: Change From Baseline in Growth and Development as Measured by Weight Percentiles	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.	Baseline; Weeks 1, 4, 8, 12, FU-4, FU-12, and FU-24
Secondary	Treatment Phase: Changes in Growth and Development as Measured by Tanner Stage Assessment From Baseline	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).	Baseline; EOT, FU-12 and FU-24
Secondary	Treatment Phase: Growth and Development as Measured by Parental Height	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.	Day 1
Secondary	Treatment Phase: Change From Baseline in Growth and Development as Measured by Bone Age	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.	Baseline; FU-24
Secondary	Treatment Phase: Swallowability of SOF/VEL as Assessed by the Participant's Ability to Swallow SOF/VEL Placebo Tablets at Baseline	A SOF/VEL FDC swallowability assessment was performed using placebo tablets at baseline.	Baseline
Secondary	Treatment Phase: Number of Participants With Acceptability of SOF/VEL as Measured by a Questionnaire to Assess Acceptability, Including Palatability at Day 1	Acceptability was assessed by numeric response marked on line between numbers 0 - 100. Higher scores indicate better acceptability and/or palatability.	Day 1
Secondary	Treatment Phase: Number of Participants With Acceptability of SOF/VEL as Measured by a Questionnaire to Assess Acceptability, Including Palatability at Week 12	Acceptability was assessed by numeric response marked on line between numbers 0 - 100. Higher scores indicate better acceptability and/or palatability.	Week 12