Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed Dose Combination in the Treatment of Hepatitis C Virus (HCV) Infection in Pediatric Participants Undergoing Cancer Chemotherapy

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02868242
• Collaborator: (none)
• Enrollment: 19
• Location: 1
• Arm: 1
• Actual Duration (Months): 29.2
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) in treating hepatitis C virus (HCV) infection in pediatric participants who are undergoing cancer chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C Virus Infection	Drug: LDV/SOF	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-label Study to Investigate the Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed Dose Combination in the Treatment of Hepatitis C Virus (HCV) Infection in Pediatric Subjects Undergoing Cancer Chemotherapy
• Actual Study Start Date: Aug 28, 2016
• Actual Primary Completion Date: Nov 12, 2018
• Actual Study Completion Date: Feb 3, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LDV/SOF Participants will receive LDV/SOF 90/400 mg fixed dose combination (FDC) (1x 90/400 mg tablet or 4 x 22.5/100 mg tablets based on swallowability assessment during screening) for 12 weeks.	Drug: LDV/SOF; Tablet(s) administered orally once daily; Other Names: Harvoni® GS-5885/GS-7977

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) [Posttreatment Week 12]

   SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 50 IU/mL) at 12 weeks after stopping study treatment.

2. Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event [First dose date up to Week 12]

Secondary Outcome Measures

1. Percentage of Participants With HCV RNA < LLOQ at 4 Weeks After Discontinuation of Therapy (SVR4) [Posttreatment Week 4]

   SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment.

2. Percentage of Participants With HCV RNA < LLOQ at 24 Weeks After Discontinuation of Therapy (SVR24) [Posttreatment Week 24]

   SVR24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment.

3. Percentage of Participants With HCV RNA < LLOQ While on Treatment [Weeks 1, 4, 8, and 12]

4. HCV RNA Change From Baseline/Day 1 [Baseline; Weeks 1, 4, 8, and 12]

5. Percentage of Participants With Virologic Failure [Baseline 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Aged 12 to <18 years

• Parent or legal guardian must provide written informed consent

• Treatment naïve or experienced children with genotype 1 or 4 HCV infection, and are on a maintenance cancer chemotherapy regimen

• Receiving a protocol-approved maintenance chemotherapy regimen for a hematological malignancy

• Chronic HCV infection (≥ 6 months) documented by medical history or liver biopsy

• Screening laboratory values within defined thresholds

• No History of solid organ or bone marrow transplantation

• No history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, variceal hemorrhage)

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Cancer Institute, Cairo University	Cairo		Egypt

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

• Study Protocol - Jun 16, 2017
• Statistical Analysis Plan - Mar 1, 2019

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02868242
• Other Study ID Numbers: GS-US-337-1904
• First Posted: Aug 16, 2016
• Last Update Posted: Mar 2, 2020
• Last Verified: Jul 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Gilead Sciences: HCV genotype 1 or 4 (GT-1 or GT-4); Direct Acting Antiviral; Combination Therapy; Hepatitis C, Chronic; Liver Diseases; Virus Diseases
• Additional relevant MeSH terms: Infections; Communicable Diseases; Hepatitis A; Hepatitis C; Hepatitis; Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at one study site in Egypt. The first participant was screened on 28 August 2016. The last study visit occurred on 03 February 2019.
Pre-assignment Detail	24 participants were screened.

Arm/Group Title	LDV/SOF
Arm/Group Description	LDV/SOF 90/400 mg fixed dose combination (FDC) orally once daily for 12 weeks
Period Title: Overall Study
STARTED	19
COMPLETED	19
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	LDV/SOF
Arm/Group Description	LDV/SOF 90/400 mg FDC orally once daily for 12 weeks
Overall Participants	19
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14 (1.8)
Sex: Female, Male (Count of Participants)
Female	3 15.8%
Male	16 84.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	19 100%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	19 100%
IL28B (Count of Participants)
CC	6 31.6%
CT	12 63.2%
TT	1 5.3%
HCV RNA (log10 IU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 IU/mL]	5.3 (1.65)
HCV RNA Category (Count of Participants)
< 800,000 IU/mL	12 63.2%
≥ 800,000 IU/mL	7 36.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
Description	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 50 IU/mL) at 12 weeks after stopping study treatment.
Time Frame	Posttreatment Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set included participants who took at least 1 dose of study drug.

Arm/Group Title	LDV/SOF
Arm/Group Description	LDV/SOF 90/400 mg FDC orally once daily for 12 weeks
Measure Participants	19
Number (95% Confidence Interval) [percentage of participants]	100.0 526.3%

2. Primary Outcome

Title	Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event
Time Frame	First dose date up to Week 12

Outcome Measure Data

Analysis Population Description

Safety Analysis Set included participants who took at least 1 dose of study drug.

Arm/Group Title	LDV/SOF
Arm/Group Description	LDV/SOF 90/400 mg FDC once daily for 12 weeks
Measure Participants	19
Number [percentage of participants]	0 0%

3. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ at 4 Weeks After Discontinuation of Therapy (SVR4)
Description	SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment.
Time Frame	Posttreatment Week 4

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	LDV/SOF
Arm/Group Description	LDV/SOF 90/400 mg FDC orally once daily for 12 weeks
Measure Participants	19
Number (95% Confidence Interval) [percentage of participants]	100.0 526.3%

4. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ at 24 Weeks After Discontinuation of Therapy (SVR24)
Description	SVR24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment.
Time Frame	Posttreatment Week 24

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	LDV/SOF
Arm/Group Description	LDV/SOF 90/400 mg FDC orally once daily for 12 weeks
Measure Participants	19
Number (95% Confidence Interval) [percentage of participants]	100.0 526.3%

5. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ While on Treatment
Time Frame	Weeks 1, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	LDV/SOF
Arm/Group Description	LDV/SOF FDC 90/400 mg orally once daily for 12 weeks
Measure Participants	19
Week 1	89.5 471.1%
Week 4	100.0 526.3%
Week 8	94.7 498.4%
Week 12	100.0 526.3%

6. Secondary Outcome

Title	HCV RNA Change From Baseline/Day 1
Time Frame	Baseline; Weeks 1, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	LDV/SOF
Arm/Group Description	LDV/SOF 90/400 mg FDC orally once daily for 12 weeks
Measure Participants	19
Change at Week 1	-3.34 (1.730)
Change at Week 4	-3.62 (1.653)
Change at Week 8	-3.36 (1.526)
Change at Week 12	-3.62 (1.653)

7. Secondary Outcome

Title	Percentage of Participants With Virologic Failure
Description	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
Time Frame	Baseline to Posttreatment Week 24

Outcome Measure Data

Analysis Population Description

Participants in Full Analysis Set were analyzed.

Arm/Group Title	LDV/SOF
Arm/Group Description	LDV/SOF 90/400 mg FDC orally once daily for 12 weeks
Measure Participants	19
Number [percentage of participants]	0 0%

Adverse Events

Time Frame	Adverse Events: First dose date up to Week 12 plus 30 days; All-Cause Mortality: First dose date up to Posttreatment Week 24
Adverse Event Reporting Description	Safety Analysis Set included participants who took at least 1 dose of study drug.
Arm/Group Title	LDV/SOF
Arm/Group Description	LDV/SOF 90/400 mg FDC orally once daily for 12 weeks
All Cause Mortality
	LDV/SOF
	Affected / at Risk (%)	# Events
Total	0/19 (0%)
Serious Adverse Events
	LDV/SOF
	Affected / at Risk (%)	# Events
Total	3/19 (15.8%)
Gastrointestinal disorders
Diarrhoea	1/19 (5.3%)
Infections and infestations
Pneumonia	2/19 (10.5%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/19 (5.3%)
Other (Not Including Serious) Adverse Events
	LDV/SOF
	Affected / at Risk (%)	# Events
Total	15/19 (78.9%)
Blood and lymphatic system disorders
Anaemia	2/19 (10.5%)
Gastrointestinal disorders
Abdominal pain	1/19 (5.3%)
Diarrhoea	3/19 (15.8%)
Lip ulceration	1/19 (5.3%)
Mouth ulceration	1/19 (5.3%)
Tongue ulceration	1/19 (5.3%)
Vomiting	3/19 (15.8%)
General disorders
Pyrexia	5/19 (26.3%)
Infections and infestations
Conjunctivitis	1/19 (5.3%)
Ear infection	1/19 (5.3%)
Oral candidiasis	1/19 (5.3%)
Pneumonia	1/19 (5.3%)
Investigations
Neutrophil count decreased	2/19 (10.5%)
Metabolism and nutrition disorders
Hypophagia	1/19 (5.3%)
Musculoskeletal and connective tissue disorders
Joint effusion	1/19 (5.3%)
Osteonecrosis	1/19 (5.3%)
Nervous system disorders
Headache	4/19 (21.1%)
Respiratory, thoracic and mediastinal disorders
Cough	2/19 (10.5%)
Productive cough	1/19 (5.3%)
Rhinorrhoea	1/19 (5.3%)
Skin and subcutaneous tissue disorders
Pruritus generalised	1/19 (5.3%)
Skin lesion	1/19 (5.3%)
Skin ulcer	1/19 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years