Ledipasvir/Sofosbuvir Fixed-Dose Combination for 12 or 24 Weeks in Genotype 1 or 4 HCV Infected Adults With Sickle Cell Disease

• ClinicalTrials.gov Identifier: NCT02301936
• Recruitment Status: Completed
• First Posted: November 26, 2014
• Results First Posted: May 25, 2017
• Last Update Posted: November 19, 2018
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hepatitis C Virus Infection
• Intervention: Drug: LDV/SOF
• Enrollment: 10

Participant Flow

Recruitment Details	Participants were enrolled at 1 study site in the United States. The first participant was screened on 02 March 2015. The last study visit occurred on 18 April 2016.
Pre-assignment Details

Arm/Group Title	LDV/SOF 12 Weeks	LDV/SOF 24 Weeks
Arm/Group Description	Treatment-naive or treatment-experienced participants without cirrhosis received ledipasvir/sofosbuvir (Harvoni®; LDV/SOF) 90/400 mg fixed dose combination (FDC) tablet once daily for 12 weeks	Treatment-experienced participants with cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks.
Period Title: Overall Study
Started	9	1
Completed	8	1
Not Completed	1	0
Reason Not Completed
Lost to Follow-up	1	0

Baseline Characteristics

Arm/Group Title		LDV/SOF 12 Weeks	LDV/SOF 24 Weeks	Total
Arm/Group Description		Treatment-naive or treatment-experienced participants without cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks	Treatment-experienced participants with cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks	Total of all reporting groups
Overall Number of Baseline Participants		9	1	10
Baseline Analysis Population Description		Safety Analysis Set: participants who took at least 1 dose of study drug.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	9 participants	1 participants	10 participants
		43 (14.9)	44 [1] (NA)	43 (14.1)
		[1] This treatment group had 1 participant only so standard deviation (SD) is not applicable.
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	9 participants	1 participants	10 participants
	Female	3 33.3%	1 100.0%	4 40.0%
	Male	6 66.7%	0 0.0%	6 60.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Black or African American	Number Analyzed	9 participants	1 participants	10 participants
		9 100.0%	1 100.0%	10 100.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Not Hispanic or Latino	Number Analyzed	9 participants	1 participants	10 participants
		9 100.0%	1 100.0%	10 100.0%
IL28b Status [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	9 participants	1 participants	10 participants
CC		1 11.1%	0 0.0%	1 10.0%
CT		2 22.2%	1 100.0%	3 30.0%
TT		6 66.7%	0 0.0%	6 60.0%
		[1] Measure Description: The CC, CT, and TT alleles are different forms of the IL28b gene.
HCV RNA; Mean (Standard Deviation); Unit of measure: Log10 IU/mL
	Number Analyzed	9 participants	1 participants	10 participants
		5.8 (0.74)	6.2 [1] (NA)	5.8 (0.71)
		[1] This treatment group had 1 participant only so SD is not applicable.
HCV RNA Category; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	9 participants	1 participants	10 participants
< 800,000 IU/mL		6 66.7%	0 0.0%	6 60.0%
≥ 800,000 IU/mL		3 33.3%	1 100.0%	4 40.0%
HCV genotype; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	9 participants	1 participants	10 participants
Genotype 1a		5 55.6%	1 100.0%	6 60.0%
Genotype 1b		1 11.1%	0 0.0%	1 10.0%
Genotype 4a/4c/4d		1 11.1%	0 0.0%	1 10.0%
Genotype 4f		1 11.1%	0 0.0%	1 10.0%
Genotype 4h		1 11.1%	0 0.0%	1 10.0%
Cirrhosis status; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	9 participants	1 participants	10 participants
Absence		9 100.0%	0 0.0%	9 90.0%
Presence		0 0.0%	1 100.0%	1 10.0%
Prior HCV Treatment Experience With Cirrhosis; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	9 participants	1 participants	10 participants
Treatment-Naive (Non-cirrhosis)		7 77.8%	0 0.0%	7 70.0%
Treatment-Experienced (Non-cirrhosis)		2 22.2%	0 0.0%	2 20.0%
Treatment-Experienced (Cirrhosis)		0 0.0%	1 100.0%	1 10.0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)
Description	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.
Time Frame	Posttreatment Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	LDV/SOF 12 Weeks	LDV/SOF 24 Weeks
Arm/Group Description:	Treatment-naive or treatment-experienced participants without cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks.	Treatment-experienced participants with cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks.
Overall Number of Participants Analyzed	9	1
Measure Type: Number; Unit of Measure: percentage of participants
	88.9	100.0

2. Primary Outcome

Title	Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Description	[Not Specified]
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	LDV/SOF 12 Weeks	LDV/SOF 24 Weeks
Arm/Group Description:	Treatment-naive or treatment-experienced participants without cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks.	Treatment-experienced participants with cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks.
Overall Number of Participants Analyzed	9	1
Measure Type: Number; Unit of Measure: percentage of participants
	0	0

3. Secondary Outcome

Title	Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4)
Description	SVR4 was defined as HCV RNA < the LLOQ 4 weeks following the last dose of study drug.
Time Frame	Posttreatment Week 4

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	LDV/SOF 12 Weeks	LDV/SOF 24 Weeks
Arm/Group Description:	Treatment-naive or treatment-experienced participants without cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks.	Treatment-experienced participants with cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks.
Overall Number of Participants Analyzed	9	1
Measure Type: Number; Unit of Measure: percentage of participants
	88.9	100.0

4. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ on Treatment
Description	[Not Specified]
Time Frame	Weeks 1, 2, 4, 8,12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title		LDV/SOF 12 Weeks	LDV/SOF 24 Weeks
Arm/Group Description:		Treatment-naive or treatment-experienced participants without cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks.	Treatment-experienced participants with cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks.
Overall Number of Participants Analyzed		9	1
Measure Type: Number; Unit of Measure: percentage of participants
Week 1	Number Analyzed	9 participants	1 participants
		33.3	0
Week 2	Number Analyzed	9 participants	1 participants
		66.7	0
Week 4	Number Analyzed	9 participants	1 participants
		88.9	100.0
Week 8	Number Analyzed	9 participants	1 participants
		88.9	100.0
Week 12	Number Analyzed	9 participants	1 participants
		100.0	100.0
Week 16	Number Analyzed	0 participants	1 participants
			100
Week 20	Number Analyzed	0 participants	1 participants
			100
Week 24	Number Analyzed	0 participants	1 participants
			100

5. Secondary Outcome

Title	HCV RNA Change From Baseline
Description	[Not Specified]
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title		LDV/SOF 12 Weeks	LDV/SOF 24 Weeks
Arm/Group Description:		Treatment-naive or treatment-experienced participants without cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks.	Treatment-experienced participants with cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks.
Overall Number of Participants Analyzed		9	1
Mean (Standard Deviation); Unit of Measure: log10 IU/mL
Change at Week 1	Number Analyzed	6 participants	1 participants
		-4.20 (0.543)	-3.86 [1] (NA)
Change at Week 2	Number Analyzed	9 participants	1 participants
		-3.86 (1.644)	-4.63 [1] (NA)
Change at Week 4	Number Analyzed	9 participants	1 participants
		-3.98 (1.694)	-5.05 [1] (NA)
Change at Week 8	Number Analyzed	9 participants	1 participants
		-4.47 (0.662)	-5.05 [1] (NA)
Change at Week 12	Number Analyzed	9 participants	1 participants
		-4.61 (0.737)	-5.05 [1] (NA)
Change at Week 16	Number Analyzed	0 participants	1 participants
			-5.05 [1] (NA)
Change at Week 20	Number Analyzed	0 participants	1 participants
			-5.05 [1] (NA)
Change at Week 24	Number Analyzed	0 participants	1 participants
			-5.05 [1] (NA)

[1]

This group had only 1 participant so SD is not applicable.

6. Secondary Outcome

Title	Percentage of Participants With Virologic Failure
Description	Virologic failure was defined as; On-treatment virologic failure HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment, > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, HCV RNA persistently ≥ LLOQ through 8 weeks of treatment (ie nonresponse); Relapse HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement
Time Frame	Up to Posttreatment Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	LDV/SOF 12 Weeks	LDV/SOF 24 Weeks
Arm/Group Description:	Treatment-naive or treatment-experienced participants without cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks.	Treatment-experienced participants with cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks.
Overall Number of Participants Analyzed	9	1
Measure Type: Number; Unit of Measure: percentage of participants
	11.1	0

7. Secondary Outcome

Title	Change From Pretreatment Assessment in Health-related Quality of Life as Evaluated by Short Form (SF-36) Health Survey Scale- Physical Component Score
Description	The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The first 6 concepts constitute the physical component summary. The total score is an average of the individual question scores, which are scaled 0-100 with lower scores representing more disability and higher scores representing less disability.
Time Frame	Weeks 4,12, 24, Posttreatment Weeks 4 and 12

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title		LDV/SOF 12 Weeks	LDV/SOF 24 Weeks
Arm/Group Description:		Treatment-naive or treatment-experienced participants without cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks.	Treatment-experienced participants with cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks.
Overall Number of Participants Analyzed		9	1
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 4	Number Analyzed	9 participants	1 participants
		1.2 (6.66)	8.5 [1] (NA)
Week 12	Number Analyzed	9 participants	1 participants
		2.7 (7.20)	5.8 [1] (NA)
Week 24	Number Analyzed	0 participants	1 participants
			2.3 [1] (NA)
Posttreatment Week 4	Number Analyzed	8 participants	1 participants
		3.5 (8.26)	0.1 [1] (NA)
Posttreatment Week 12	Number Analyzed	8 participants	1 participants
		0.7 (12.46)	5.5 [1] (NA)

[1]

This group had only 1 participant so SD is not applicable.

8. Secondary Outcome

Title	Change From Pretreatment Assessment in Health-related Quality of Life as Evaluated by Short Form (SF-36) Health Survey Scale- Mental Component Score
Description	The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The last 5 concepts constitute the mental component summary. The total score is an average of the individual question scores, which are scaled 0-100 with lower score representing more disability and higher scores representing less disability.
Time Frame	Weeks 4,12, 24, Posttreatment Weeks 4 and 12

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title		LDV/SOF 12 Weeks	LDV/SOF 24 Weeks
Arm/Group Description:		Treatment-naive or treatment-experienced participants without cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks.	Treatment-experienced participants with cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks.
Overall Number of Participants Analyzed		9	1
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 4	Number Analyzed	9 participants	1 participants
		2.2 (8.88)	-4.7 [1] (NA)
Week 12	Number Analyzed	9 participants	1 participants
		3.2 (8.14)	-3.3 [1] (NA)
Week 24	Number Analyzed	0 participants	1 participants
			-3.9 [1] (NA)
Posttreatment Week 4	Number Analyzed	8 participants	1 participants
		2.2 (9.69)	-4.6 [1] (NA)
Posttreatment Week 12	Number Analyzed	8 participants	1 participants
		2.4 (6.53)	-5.0 [1] (NA)

[1]

This group had only 1 participant so SD is not applicable.

9. Secondary Outcome

Title	Change From Pretreatment Assessment in Health-related Quality of Life as Evaluated by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)
Description	The FACIT-Fatigue score was measured using a 40-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants scored each item on a 5-point scale from 0 (Not at all) to 4 (Very much). The FACIT-F total score was calculated by taking the sum of all 40 individual scores and ranged from 0-160, with higher scores indicating better quality of life.
Time Frame	Weeks 4,12, 24, Posttreatment Weeks 4 and 12

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title		LDV/SOF 12 Weeks	LDV/SOF 24 Weeks
Arm/Group Description:		Treatment-naive or treatment-experienced participants without cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks.	Treatment-experienced participants with cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks.
Overall Number of Participants Analyzed		9	1
Mean (Standard Deviation); Unit of Measure: units on a scale
Week 4	Number Analyzed	8 participants	1 participants
		4.6 (13.86)	-0.2 [1] (NA)
Week 12	Number Analyzed	8 participants	1 participants
		9.8 (17.15)	14.5 [1] (NA)
Week 24	Number Analyzed	0 participants	1 participants
			11.7 [1] (NA)
Posttreatment Week 4	Number Analyzed	7 participants	1 participants
		13.0 (17.20)	13.2 [1] (NA)
Posttreatment Week 24	Number Analyzed	7 participants	1 participants
		8.5 (6.32)	5.0 [1] (NA)

[1]

This group had only 1 participant so SD is not applicable.

Adverse Events

Time Frame	Up to 24 weeks plus 30 days
Adverse Event Reporting Description	Safety Analysis Set
Arm/Group Title	LDV/SOF 12 Weeks	LDV/SOF 24 Weeks
Arm/Group Description	Treatment-naive or treatment-experienced participants without cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks.	Treatment-experienced participants with cirrhosis received LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks.
All-Cause Mortality
	LDV/SOF 12 Weeks	LDV/SOF 24 Weeks
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/9 (0.00%)	0/1 (0.00%)
Serious Adverse Events
	LDV/SOF 12 Weeks	LDV/SOF 24 Weeks
	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/9 (11.11%)	0/1 (0.00%)
Blood and lymphatic system disorders
Sickle cell anaemia with crisis † 1	1/9 (11.11%)	0/1 (0.00%)
1 Term from vocabulary, MedDRA 19.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	LDV/SOF 12 Weeks	LDV/SOF 24 Weeks
	Affected / at Risk (%)	Affected / at Risk (%)
Total	6/9 (66.67%)	1/1 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	1/9 (11.11%)	0/1 (0.00%)
Sickle cell anaemia with crisis † 1	1/9 (11.11%)	0/1 (0.00%)
Eye disorders
Eye discharge † 1	0/9 (0.00%)	1/1 (100.00%)
Gastrointestinal disorders
Nausea † 1	2/9 (22.22%)	0/1 (0.00%)
General disorders
Fatigue † 1	1/9 (11.11%)	1/1 (100.00%)
Pyrexia † 1	1/9 (11.11%)	0/1 (0.00%)
Infections and infestations
Atypical pneumonia † 1	1/9 (11.11%)	0/1 (0.00%)
Pneumonia † 1	0/9 (0.00%)	1/1 (100.00%)
Musculoskeletal and connective tissue disorders
Back pain † 1	1/9 (11.11%)	0/1 (0.00%)
Flank pain † 1	1/9 (11.11%)	0/1 (0.00%)
Musculoskeletal chest pain † 1	0/9 (0.00%)	1/1 (100.00%)
Nervous system disorders
Headache † 1	6/9 (66.67%)	0/1 (0.00%)
Psychiatric disorders
Insomnia † 1	0/9 (0.00%)	1/1 (100.00%)
Respiratory, thoracic and mediastinal disorders
Epistaxis † 1	1/9 (11.11%)	0/1 (0.00%)
1 Term from vocabulary, MedDRA 19.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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

Results Point of Contact

• Name/Title: Clinical Trial Disclosures
• Organization: Gilead Sciences
• EMail: ClinicalTrialDisclosures@gilead.com

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02301936
• Other Study ID Numbers: GS-US-337-1405
• First Submitted: November 24, 2014
• First Posted: November 26, 2014
• Results First Submitted: April 18, 2017
• Results First Posted: May 25, 2017
• Last Update Posted: November 19, 2018