Trial Outcomes & Findings for Safety, Tolerability and Efficacy of Sofosbuvir, Velpatasvir, and Voxilaprevir in Subjects With Previous DAA Experience (NCT NCT02745535)

NCT ID: NCT02745535

Last Updated: 2022-03-10

Results Overview

Number of participants with grade 3 and 4 adverse events during treatment with and/or within 30 of completion of SOF/VEL/VOX in HCV infected

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 77 participants
• Primary outcome timeframe: up to 16 weeks
• Results posted on: 2022-03-10

Participant Flow

Study enrollment opened 5-May-2016 and closed 24-Jan-2018. All study visits were done in an outpatient medical clinic in Baltimore or Washington DC.

Participants infected with chronic hepatitis C (HCV), genotype 1, who previously were treated with unsuccessful combination DAA-based therapy were enrolled in the study. Subjects included HCV mono-infection, HCV/HIV co-infection or HCV/hepatitis B (HBV) co-infection or HCV/HIV/HBV triple-infected patients.

Participant milestones

Measure	SOF/VEL/VOX Fixed dose combination of SOF/VEL/VOX (Sofosbuvir 400mg/Velpatasvir 100mg/ Voxilaprevir 100mg) dosed once daily for 12 weeks in participants with chronic hepatitis c previously exposed to direct acting antivirals (DAA).
Overall Study STARTED	77
Overall Study Sustained Virologic Repsonse	70
Overall Study COMPLETED	71
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Measure	SOF/VEL/VOX Fixed dose combination of SOF/VEL/VOX (Sofosbuvir 400mg/Velpatasvir 100mg/ Voxilaprevir 100mg) dosed once daily for 12 weeks in participants with chronic hepatitis c previously exposed to direct acting antivirals (DAA).
Overall Study Death	1
Overall Study Adverse Event	3
Overall Study Lost to Follow-up	2

Baseline Characteristics

Safety, Tolerability and Efficacy of Sofosbuvir, Velpatasvir, and Voxilaprevir in Subjects With Previous DAA Experience

Baseline characteristics by cohort

Measure	SOF/VEL/VOX n=77 Participants Fixed dose combination of SOF/VEL/VOX (Sofosbuvir 400mg/Velpatasvir 100mg/ Voxilaprevir 100mg) dosed once daily for 12 weeks in participants with chronic hepatitis c previously exposed to direct acting antivirals (DAA).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	64 Participants n=5 Participants
Age, Categorical >=65 years	13 Participants n=5 Participants
Age, Continuous	60 years STANDARD_DEVIATION 8.0 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	64 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	76 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	66 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	77 participants n=5 Participants
Compensated cirrhotic	31 Participants n=5 Participants
Co-infected with HIV	22 Participants n=5 Participants
Coinfected with HIV and hepatitis B	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 16 weeks

Population: All participants who received at least one dose of treatment.

Number of participants with grade 3 and 4 adverse events during treatment with and/or within 30 of completion of SOF/VEL/VOX in HCV infected

Outcome measures

Measure	SOF/VEL/VOX n=77 Participants Fixed dose combination of SOF/VEL/VOX (Sofosbuvir 400mg/Velpatasvir 100mg/ Voxilaprevir 100mg) dosed once daily for 12 weeks in participants with chronic hepatitis c previously exposed to direct acting antivirals (DAA).
Number of Participants With Grade 3 and 4 Adverse Events	12 Participants

PRIMARY outcome

Timeframe: Post-treatment week 12

Population: All participants who took at least one dose of study medication.

Intention to treat (ITT) analysis. Sustained Virologic Response as measure by an undetectable HCV RNA level 12 weeks after completion of therapy.

Outcome measures

Measure	SOF/VEL/VOX n=77 Participants Fixed dose combination of SOF/VEL/VOX (Sofosbuvir 400mg/Velpatasvir 100mg/ Voxilaprevir 100mg) dosed once daily for 12 weeks in participants with chronic hepatitis c previously exposed to direct acting antivirals (DAA).
Number of Participants Who Achieve Sustained Virologic Response (SVR) 12 Weeks After Completion of Therapy (SVR12)	70 Participants

SECONDARY outcome

Timeframe: Week 12

Per protocol analysis. End of Treatment Virologic Response as measure by an undetectable HCV RNA level completion of therapy.

Outcome measures

Measure	SOF/VEL/VOX n=71 Participants Fixed dose combination of SOF/VEL/VOX (Sofosbuvir 400mg/Velpatasvir 100mg/ Voxilaprevir 100mg) dosed once daily for 12 weeks in participants with chronic hepatitis c previously exposed to direct acting antivirals (DAA).
Number of Participants Who Achieve End of Treatment Virologic Response (ETR) at Completion of Therapy.	71 Participants

SECONDARY outcome

Timeframe: Post-treatment week 4

Per protocol analysis. Sustained Virologic Response as measure by an undetectable HCV RNA level 4 weeks after completion of therapy.

Outcome measures

Measure	SOF/VEL/VOX n=71 Participants Fixed dose combination of SOF/VEL/VOX (Sofosbuvir 400mg/Velpatasvir 100mg/ Voxilaprevir 100mg) dosed once daily for 12 weeks in participants with chronic hepatitis c previously exposed to direct acting antivirals (DAA).
Number of Participants Who Achieve Sustained Virologic Response (SVR) 4 Weeks After Completion of Therapy.	70 Participants

SECONDARY outcome

Timeframe: Post-treatment week 24

Per protocol analysis. Sustained Virologic Response as measure by an undetectable HCV RNA level 24 weeks after completion of therapy.

Outcome measures

Measure	SOF/VEL/VOX n=71 Participants Fixed dose combination of SOF/VEL/VOX (Sofosbuvir 400mg/Velpatasvir 100mg/ Voxilaprevir 100mg) dosed once daily for 12 weeks in participants with chronic hepatitis c previously exposed to direct acting antivirals (DAA).
Number of Participants Who Achieve Sustained Virologic Response (SVR) 24 Weeks After Completion of Therapy.	70 Participants

Adverse Events

SOF/VEL/VOX

Serious events: 12 serious events

Other events: 75 other events

Deaths: 1 deaths

Serious adverse events

Measure	SOF/VEL/VOX n=77 participants at risk Fixed dose combination of SOF/VEL/VOX (Sofosbuvir 400mg/Velpatasvir 100mg/ Voxilaprevir 100mg) dosed once daily for 12 weeks in participants with chronic hepatitis c previously exposed to direct acting antivirals (DAA).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	1.3% 1/77 • Number of events 1 • Adverse events were monitored and reported from day first dose of study medication was taken until 30 days after last dose, which was an average of 16 weeks. \\Participants were assessed for adverse events at every follow up visit. Adverse events were monitored from the time of informed consent until last study visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	1.3% 1/77 • Number of events 1 • Adverse events were monitored and reported from day first dose of study medication was taken until 30 days after last dose, which was an average of 16 weeks. \\Participants were assessed for adverse events at every follow up visit. Adverse events were monitored from the time of informed consent until last study visit.
Vascular disorders Hypertensive stroke	1.3% 1/77 • Number of events 1 • Adverse events were monitored and reported from day first dose of study medication was taken until 30 days after last dose, which was an average of 16 weeks. \\Participants were assessed for adverse events at every follow up visit. Adverse events were monitored from the time of informed consent until last study visit.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension, exacerbation	1.3% 1/77 • Number of events 1 • Adverse events were monitored and reported from day first dose of study medication was taken until 30 days after last dose, which was an average of 16 weeks. \\Participants were assessed for adverse events at every follow up visit. Adverse events were monitored from the time of informed consent until last study visit.
Injury, poisoning and procedural complications Subderal hematoma, traumatic	1.3% 1/77 • Number of events 1 • Adverse events were monitored and reported from day first dose of study medication was taken until 30 days after last dose, which was an average of 16 weeks. \\Participants were assessed for adverse events at every follow up visit. Adverse events were monitored from the time of informed consent until last study visit.
Investigations Aspartate aminotransferase >5xULN	1.3% 1/77 • Number of events 1 • Adverse events were monitored and reported from day first dose of study medication was taken until 30 days after last dose, which was an average of 16 weeks. \\Participants were assessed for adverse events at every follow up visit. Adverse events were monitored from the time of informed consent until last study visit.
Investigations Creatinine >2x baseline	2.6% 2/77 • Number of events 2 • Adverse events were monitored and reported from day first dose of study medication was taken until 30 days after last dose, which was an average of 16 weeks. \\Participants were assessed for adverse events at every follow up visit. Adverse events were monitored from the time of informed consent until last study visit.
Investigations Glucose level >250mg/dL	2.6% 2/77 • Number of events 2 • Adverse events were monitored and reported from day first dose of study medication was taken until 30 days after last dose, which was an average of 16 weeks. \\Participants were assessed for adverse events at every follow up visit. Adverse events were monitored from the time of informed consent until last study visit.
Investigations INR >2x ULN	2.6% 2/77 • Number of events 2 • Adverse events were monitored and reported from day first dose of study medication was taken until 30 days after last dose, which was an average of 16 weeks. \\Participants were assessed for adverse events at every follow up visit. Adverse events were monitored from the time of informed consent until last study visit.

Other adverse events

Measure	SOF/VEL/VOX n=77 participants at risk Fixed dose combination of SOF/VEL/VOX (Sofosbuvir 400mg/Velpatasvir 100mg/ Voxilaprevir 100mg) dosed once daily for 12 weeks in participants with chronic hepatitis c previously exposed to direct acting antivirals (DAA).
General disorders Fatigue	27.3% 21/77 • Number of events 21 • Adverse events were monitored and reported from day first dose of study medication was taken until 30 days after last dose, which was an average of 16 weeks. \\Participants were assessed for adverse events at every follow up visit. Adverse events were monitored from the time of informed consent until last study visit.
Nervous system disorders Headache	24.7% 19/77 • Number of events 19 • Adverse events were monitored and reported from day first dose of study medication was taken until 30 days after last dose, which was an average of 16 weeks. \\Participants were assessed for adverse events at every follow up visit. Adverse events were monitored from the time of informed consent until last study visit.
Gastrointestinal disorders Diarrhea	20.8% 16/77 • Number of events 16 • Adverse events were monitored and reported from day first dose of study medication was taken until 30 days after last dose, which was an average of 16 weeks. \\Participants were assessed for adverse events at every follow up visit. Adverse events were monitored from the time of informed consent until last study visit.
Gastrointestinal disorders Abdominal pain	9.1% 7/77 • Number of events 7 • Adverse events were monitored and reported from day first dose of study medication was taken until 30 days after last dose, which was an average of 16 weeks. \\Participants were assessed for adverse events at every follow up visit. Adverse events were monitored from the time of informed consent until last study visit.
Gastrointestinal disorders Nausea	9.1% 7/77 • Number of events 7 • Adverse events were monitored and reported from day first dose of study medication was taken until 30 days after last dose, which was an average of 16 weeks. \\Participants were assessed for adverse events at every follow up visit. Adverse events were monitored from the time of informed consent until last study visit.
Gastrointestinal disorders Constipation	6.5% 5/77 • Number of events 5 • Adverse events were monitored and reported from day first dose of study medication was taken until 30 days after last dose, which was an average of 16 weeks. \\Participants were assessed for adverse events at every follow up visit. Adverse events were monitored from the time of informed consent until last study visit.

Additional Information

Dr. Eleanor Wilson

Institute of Human Virology, University of Maryland

Phone: 1(410)706-1710

Email: eleanor.wilson@ihv.umaryland.edu

Results disclosure agreements

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