Trial Outcomes & Findings for Safety and Efficacy of Ledipasvir/Sofosbuvir (LDV/SOF) Fixed-Dose Combination (FDC) for 6 Weeks in Adults With Acute Genotype 1 or 4 Hepatitis C Virus (HCV) and Chronic Human Immunodeficiency Virus (HIV)-1 Co-Infection (NCT NCT02457611)

NCT ID: NCT02457611

Last Updated: 2018-11-16

Results Overview

SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 26 participants
• Primary outcome timeframe: Posttreatment Week 12
• Results posted on: 2018-11-16

Participant Flow

Participants were enrolled at study sites in Germany and the United Kingdom. The first participant was screened on 11 June 2015. The last study visit occurred on 8 January 2016.

34 participants were screened.

Participant milestones

Measure	LDV/SOF Ledipasvir/sofosbuvir (Harvoni®; LDV/SOF) (90/400 mg) fixed-dose combination (FDC) tablet administered once daily for 6 weeks
Overall Study STARTED	26
Overall Study COMPLETED	23
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	LDV/SOF Ledipasvir/sofosbuvir (Harvoni®; LDV/SOF) (90/400 mg) fixed-dose combination (FDC) tablet administered once daily for 6 weeks
Overall Study Lost to Follow-up	3

Baseline Characteristics

Safety and Efficacy of Ledipasvir/Sofosbuvir (LDV/SOF) Fixed-Dose Combination (FDC) for 6 Weeks in Adults With Acute Genotype 1 or 4 Hepatitis C Virus (HCV) and Chronic Human Immunodeficiency Virus (HIV)-1 Co-Infection

Baseline characteristics by cohort

Measure	LDV/SOF n=26 Participants LDV/SOF 90/400 mg FDC tablet administered once daily for 6 weeks
Age, Continuous	41 years STANDARD_DEVIATION 8.8 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants
Race/Ethnicity, Customized White	24 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	22 Participants n=5 Participants
Race/Ethnicity, Customized Not Disclosed	3 Participants n=5 Participants
Region of Enrollment United Kingdom	11 Participants n=5 Participants
Region of Enrollment Germany	15 Participants n=5 Participants
IL28b Status CC	12 Participants n=5 Participants
IL28b Status CT	11 Participants n=5 Participants
IL28b Status TT	3 Participants n=5 Participants
HCV Genotype Genotype 1a	19 Participants n=5 Participants
HCV Genotype Genotype 4	7 Participants n=5 Participants
HCV RNA	5.4 log10 IU/mL STANDARD_DEVIATION 1.60 • n=5 Participants
HCV RNA Category < 800,000 IU/mL	14 Participants n=5 Participants
HCV RNA Category >= 800,000 IU/mL	12 Participants n=5 Participants
CD4 Counts	675 cells/uL STANDARD_DEVIATION 251.3 • n=5 Participants

PRIMARY outcome

Timeframe: Posttreatment Week 12

Population: Full Analysis Set: participants with genotype 1 or 4 HCV infection who were enrolled into the study and received at least 1 dose of study drug

SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.

Outcome measures

Measure	LDV/SOF n=26 Participants LDV/SOF 90/400 mg FDC tablet administered once daily for 6 weeks
Percentage of Participants With Sustained Virologic Response 12 Weeks After Completion of Treatment (SVR12)	76.9 percentage of participants Interval 56.4 to 91.0

PRIMARY outcome

Timeframe: Up to 6 weeks

Population: Safety Analysis Set

Outcome measures

Measure	LDV/SOF n=26 Participants LDV/SOF 90/400 mg FDC tablet administered once daily for 6 weeks
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event	0 percentage of participants

SECONDARY outcome

Timeframe: Posttreatment Week 4

Population: Full Analysis Set

SVR4 was defined as HCV RNA < LLOQ 4 weeks after the last dose of study drug.

Outcome measures

Measure	LDV/SOF n=26 Participants LDV/SOF 90/400 mg FDC tablet administered once daily for 6 weeks
Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Study Treatment (SVR4)	84.6 percentage of participants Interval 65.1 to 95.6

SECONDARY outcome

Timeframe: Weeks 2, 4, and 6

Population: Full Analysis Set

Outcome measures

Measure	LDV/SOF n=26 Participants LDV/SOF 90/400 mg FDC tablet administered once daily for 6 weeks
Percentage of Participants With HCV RNA < LLOQ on Treatment Week 2	73.1 percentage of participants Interval 52.2 to 88.4
Percentage of Participants With HCV RNA < LLOQ on Treatment Week 4	88.5 percentage of participants Interval 69.8 to 97.6
Percentage of Participants With HCV RNA < LLOQ on Treatment Week 6	96.2 percentage of participants Interval 80.4 to 99.9

SECONDARY outcome

Timeframe: Baseline; Weeks 2, 4, and 6

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

Outcome measures

Measure	LDV/SOF n=26 Participants LDV/SOF 90/400 mg FDC tablet administered once daily for 6 weeks
Change From Baseline in HCV RNA at Weeks 2, 4, and 6 Change at Week 2	-4.01 log10 IU/mL Standard Deviation 1.497
Change From Baseline in HCV RNA at Weeks 2, 4, and 6 Change at Week 4	-4.16 log10 IU/mL Standard Deviation 1.583
Change From Baseline in HCV RNA at Weeks 2, 4, and 6 Change at Week 6	-4.17 log10 IU/mL Standard Deviation 1.583

SECONDARY outcome

Timeframe: Up to Posttreatment Week 12

Population: Full Analysis Set

Virologic failure was defined as:

• On-treatment virologic failure

• confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment (ie, breakthrough),
• confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment (ie, rebound),
• HCV RNA persistently ≥ LLOQ through end 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

Outcome measures

Measure	LDV/SOF n=26 Participants LDV/SOF 90/400 mg FDC tablet administered once daily for 6 weeks
Percentage of Participants With Virologic Failure	15.4 percentage of participants

SECONDARY outcome

Timeframe: Day 1; Week 6

Population: Safety Analysis Set

Participants with HIV virologic rebound was defined as participants with at least two HIV RNA ≥ 400 copies/mL at 2 consecutive post-baseline visits which are at least 2 weeks apart based on actual dates.

Outcome measures

Measure	LDV/SOF n=26 Participants LDV/SOF 90/400 mg FDC tablet administered once daily for 6 weeks
Change in HIV RNA From Day 1 to End of Treatment as Assessed by Proportion of Participants Who Had Confirmed HIV Virologic Rebound During the Study.	0 Participants

SECONDARY outcome

Timeframe: Weeks 2, 4, 6, and Posttreatment Week 4

Population: Participants in the Safety Analysis Set who had HIV-1 RNA \< 50 copies/mL at Baseline were analyzed.

Outcome measures

Measure	LDV/SOF n=21 Participants LDV/SOF 90/400 mg FDC tablet administered once daily for 6 weeks
Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment and at Posttreatment Week 4 Week 2	100.0 percentage of participants Interval 83.9 to 100.0
Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment and at Posttreatment Week 4 Week 4	100.0 percentage of participants Interval 83.9 to 100.0
Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment and at Posttreatment Week 4 Week 6	95.2 percentage of participants Interval 76.2 to 99.9
Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment and at Posttreatment Week 4 Posttreatment Week 4	100.0 percentage of participants Interval 83.9 to 100.0

SECONDARY outcome

Timeframe: Baseline; Week 6; Posttreatment Week 4

Population: Participants in the Safety Analysis Set with available data were analyzed.

Outcome measures

Measure	LDV/SOF n=26 Participants LDV/SOF 90/400 mg FDC tablet administered once daily for 6 weeks
Percent Change From Baseline in CD4 T-cell Count at the End of Treatment and at Posttreatment Week 4 Change at Week 6	-0.3 percent change Standard Deviation 4.91
Percent Change From Baseline in CD4 T-cell Count at the End of Treatment and at Posttreatment Week 4 Change at Posttreatment Week 4	0.4 percent change Standard Deviation 4.08

Adverse Events

LDV/SOF

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Measure	LDV/SOF n=26 participants at risk LDV/SOF 90/400 mg FDC tablet administered once daily for 6 weeks
General disorders Pyrexia	3.8% 1/26 • Up to 6 weeks plus 30 days Safety Analysis Set
Nervous system disorders Loss of consciousness	3.8% 1/26 • Up to 6 weeks plus 30 days Safety Analysis Set
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	3.8% 1/26 • Up to 6 weeks plus 30 days Safety Analysis Set
Vascular disorders Thrombophlebitis	3.8% 1/26 • Up to 6 weeks plus 30 days Safety Analysis Set

Other adverse events

Measure	LDV/SOF n=26 participants at risk LDV/SOF 90/400 mg FDC tablet administered once daily for 6 weeks
Gastrointestinal disorders Diarrhoea	11.5% 3/26 • Up to 6 weeks plus 30 days Safety Analysis Set
Gastrointestinal disorders Nausea	11.5% 3/26 • Up to 6 weeks plus 30 days Safety Analysis Set
Gastrointestinal disorders Toothache	7.7% 2/26 • Up to 6 weeks plus 30 days Safety Analysis Set
General disorders Fatigue	26.9% 7/26 • Up to 6 weeks plus 30 days Safety Analysis Set
Infections and infestations Nasopharyngitis	26.9% 7/26 • Up to 6 weeks plus 30 days Safety Analysis Set
Infections and infestations Oral herpes	7.7% 2/26 • Up to 6 weeks plus 30 days Safety Analysis Set
Infections and infestations Syphilis	7.7% 2/26 • Up to 6 weeks plus 30 days Safety Analysis Set
Nervous system disorders Headache	23.1% 6/26 • Up to 6 weeks plus 30 days Safety Analysis Set
Psychiatric disorders Insomnia	11.5% 3/26 • Up to 6 weeks plus 30 days Safety Analysis Set

Additional Information

Clinical Trial Disclosures

Gilead Sciences

Email: ClinicalTrialDisclosures@gilead.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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
• Publication restrictions are in place

Restriction type: OTHER