Trial Outcomes & Findings for Randomised Study of Interferon-free Treatment for Recently Acquired Hepatitis C in PWID and People With HIV Coinfection. (NCT NCT02625909)

Last Updated: 2021-11-24

Results Overview

To evaluate the proportion of participants with HCV RNA below the level of quantification at 12 weeks post treatment following SOF/VEL for 6 weeks as compared with 12 weeks in people with recent HCV infection- among intention-to-treat (ITT) population The ITT population included all randomized participants, with loss to follow-up deemed treatment failure.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

222 participants

Primary outcome timeframe

12 weeks post treatment

Results posted on

2021-11-24

Participant Flow

Total 277 participants screened for protocol eligibility. Of 277 participants, 55 participants did not meet the protocol eligibility and excluded. Hence, a total 222 participants were enrolled into the study.

Of 277 participants screened for eligibility,55 were excluded \[not meeting inclusion criteria (n=38),consent withdrawn/refusal (n=7),lost to follow-up (n=4), other (n=6)\] and 26 commenced treatment but not randomized were excluded \[between baseline (BSL) and wk 6 at Data Safety \& Monitoring Board (DSMB) advice (n=9),in screening at DSMB advice (n=12),lost to follow-up before wk 6 (n=5)\]. 196 were randomized with 8 (4 in each arm) excluded following DSMB advice,hence a final population of 188.

Participant milestones

Participant milestones
Measure	Drug: Sofosbuvir/Velpatasvir (SOF/VEL) for 6 Weeks Open-label sofosbuvir/velpatasvir (SOF/VEL) 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the short treatment duration arm (A) for 6 weeks. SOF/VEL for 6 weeks: Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm A (6 weeks short treatment duration).	Drug: Sofosbuvir/Velpatasvir (SOF/VEL) for 12 Weeks Open-label sofosbuvir/velpatasvir (SOF/VEL) 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the standard treatment duration arm (B) for 12 weeks. SOF/VEL for 12 weeks: Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm B (12 weeks standard treatment duration).
Overall Study STARTED	93	95
Overall Study COMPLETED	76	86
Overall Study NOT COMPLETED	17	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Drug: Sofosbuvir/Velpatasvir (SOF/VEL) for 6 Weeks Open-label sofosbuvir/velpatasvir (SOF/VEL) 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the short treatment duration arm (A) for 6 weeks. SOF/VEL for 6 weeks: Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm A (6 weeks short treatment duration).	Drug: Sofosbuvir/Velpatasvir (SOF/VEL) for 12 Weeks Open-label sofosbuvir/velpatasvir (SOF/VEL) 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the standard treatment duration arm (B) for 12 weeks. SOF/VEL for 12 weeks: Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm B (12 weeks standard treatment duration).
Overall Study Death	2	0
Overall Study Lost to Follow-up	3	5
Overall Study Lack of Efficacy	9	2
Overall Study Reinfection	3	2

Baseline Characteristics

Randomised Study of Interferon-free Treatment for Recently Acquired Hepatitis C in PWID and People With HIV Coinfection.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Drug: Sofosbuvir/Velpatasvir (SOF/VEL) for 6 Weeks n=93 Participants Open-label sofosbuvir/velpatasvir (SOF/VEL) 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the short treatment duration arm (A) for 6 weeks. SOF/VEL for 6 weeks: Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm A (6 weeks short treatment duration).	Drug: Sofosbuvir/Velpatasvir (SOF/VEL) for 12 Weeks n=95 Participants Open-label sofosbuvir/velpatasvir (SOF/VEL) 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the standard treatment duration arm (B) for 12 weeks. SOF/VEL for 12 weeks: Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm B (12 weeks standard treatment duration).	Total n=188 Participants Total of all reporting groups
Age, Continuous	44.2 years STANDARD_DEVIATION 10.3 • n=5 Participants	43.4 years STANDARD_DEVIATION 10.2 • n=7 Participants	43.8 years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	91 Participants n=5 Participants	91 Participants n=7 Participants	182 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian/White	79 Participants n=5 Participants	78 Participants n=7 Participants	157 Participants n=5 Participants
Race/Ethnicity, Customized Asian	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Other	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Race/Ethnicity, Customized Unknown or not reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	3 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	89 Participants n=5 Participants	87 Participants n=7 Participants	176 Participants n=5 Participants
Type of hepatitis C virus (HCV) infection Primary infection	59 Participants n=5 Participants	60 Participants n=7 Participants	119 Participants n=5 Participants
Type of hepatitis C virus (HCV) infection Reinfection	34 Participants n=5 Participants	35 Participants n=7 Participants	69 Participants n=5 Participants
Human Immunodeficiency Virus (HIV) positive	65 Participants n=5 Participants	65 Participants n=7 Participants	130 Participants n=5 Participants
Baseline HCV ribonucleic acid (RNA)	5.6 log10 IU/ml n=5 Participants	5.4 log10 IU/ml n=7 Participants	5.6 log10 IU/ml n=5 Participants
HCV genotype 1a	58 Participants n=5 Participants	57 Participants n=7 Participants	115 Participants n=5 Participants
HCV genotype 1b	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
HCV genotype 1 unknown subtype	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
HCV genotype 2	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
HCV genotype 3	15 Participants n=5 Participants	17 Participants n=7 Participants	32 Participants n=5 Participants
HCV genotype 4	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants
Mode of HCV exposure Injecting drug use	18 Participants n=5 Participants	22 Participants n=7 Participants	40 Participants n=5 Participants
Mode of HCV exposure Sexual exposure with person(s) of opposite sex	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Mode of HCV exposure Sexual exposure with person(s) of same sex	69 Participants n=5 Participants	66 Participants n=7 Participants	135 Participants n=5 Participants
Mode of HCV exposure Occupational (needle stick or other exposure)	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Mode of HCV exposure Use of non-injectable recreational drugs	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Mode of HCV exposure Other	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Max alanine aminotransferase (ALT)	364 International units per liter (IU/L) n=5 Participants	360 International units per liter (IU/L) n=7 Participants	362 International units per liter (IU/L) n=5 Participants
Baseline ALT	114 International units per liter (IU/L) n=5 Participants	128 International units per liter (IU/L) n=7 Participants	126 International units per liter (IU/L) n=5 Participants
Symptomatic presentation	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Estimated duration of infection to baseline	26.1 weeks n=5 Participants	25.0 weeks n=7 Participants	25.8 weeks n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks post treatment

Outcome measures

Outcome measures
Measure	Drug: SOF/VEL for 6 Weeks n=93 Participants Open-label SOF/VEL 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the short treatment duration arm (A) for 6 weeks. SOF/VEL for 6 weeks: Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm A (6 weeks short treatment duration).	Drug: SOF/VEL for 12 Weeks n=95 Participants Open-label SOF/VEL 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the standard treatment duration arm (B) for 12 weeks. SOF/VEL for 12 weeks: Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm B (12 weeks standard treatment duration).
Number of Participants With Undetectable HCV RNA at 12 Weeks Post End of Treatment (SVR12) Following SOF/VEL for 6 Weeks as Compared With 12 Weeks in People With Recent HCV Infection- Among Intention-to-treat (ITT) Population	76 Participants	86 Participants

SECONDARY outcome

Timeframe: 12 Weeks Post End of Treatment

Population: The modified ITT population included participants in the ITT population, but excluded those with non-virological reasons for treatment failure (including death and loss to follow-up) and reinfection. 8 out of 93 individuals in short arm (3 reinfections, 2 deaths and 3 lost to follow ups) and 7 out of 95 individuals in standard arm (2 reinfections and 5 lost to follow ups) were excluded. Therefore the final number for analysis population were 85 and 88 in short and standard arm, respectively.

To evaluate the proportion of participants with HCV RNA below the level of quantification at 12 weeks post treatment following SOF/VEL for 6 weeks as compared with 12 weeks in people with recent HCV infection- among modified intention-to-treat (ITT) population The modified ITT population included participants in the ITT population, but excluded those with non-virological reasons for treatment failure (including death and loss to follow-up) and reinfection.

Outcome measures

Outcome measures
Measure	Drug: SOF/VEL for 6 Weeks n=85 Participants Open-label SOF/VEL 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the short treatment duration arm (A) for 6 weeks. SOF/VEL for 6 weeks: Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm A (6 weeks short treatment duration).	Drug: SOF/VEL for 12 Weeks n=88 Participants Open-label SOF/VEL 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the standard treatment duration arm (B) for 12 weeks. SOF/VEL for 12 weeks: Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm B (12 weeks standard treatment duration).
Number of Participants With Undetectable HCV RNA at 12 Weeks Post End of Treatment (SVR12) Following SOF/VEL for 6 Weeks as Compared With 12 Weeks in People With Recent HCV Infection- Among Modified Intention-to-treat (ITT) Population	76 Participants	86 Participants

SECONDARY outcome

Timeframe: End of treatment - week 6 of the shortened treatment duration arm, and week 12 of the standard treatment duration arm

To evaluate the proportion of participants with HCV RNA below the level of quantification at end of treatment of SOF/VEL for 6 Weeks as compared With 12 Weeks in People With Recent HCV Infection The ITT population included all randomized participants, with loss to follow-up deemed treatment failure.

Outcome measures

Outcome measures
Measure	Drug: SOF/VEL for 6 Weeks n=93 Participants Open-label SOF/VEL 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the short treatment duration arm (A) for 6 weeks. SOF/VEL for 6 weeks: Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm A (6 weeks short treatment duration).	Drug: SOF/VEL for 12 Weeks n=95 Participants Open-label SOF/VEL 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the standard treatment duration arm (B) for 12 weeks. SOF/VEL for 12 weeks: Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm B (12 weeks standard treatment duration).
Number of Participants With Undetectable HCV RNA at End of Treatment (ETR) of SOF/VEL for 6 Weeks as Compared With 12 Weeks in People With Recent HCV Infection- Among Intention-to-treat (ITT) Population	85 Participants	87 Participants

SECONDARY outcome

Timeframe: 12 weeks post treatment

Population: The per protocol population included participants who received \>90% of scheduled treatment for \>90% of the scheduled treatment period with follow-up virologic data at SVR12 (excluding reinfection and retreatments) which was 74 and 77 for short and standard arm, respectively.

To evaluate the proportion of participants with HCV RNA below the level of quantification at 12 weeks post treatment following SOF/VEL for 6 weeks as compared with 12 weeks in people with recent HCV infection- among Per Protocol (PP) population The per protocol population included participants who received \>90% of scheduled treatment for \>90% of the scheduled treatment period with follow-up virologic data at SVR12 (excluding reinfection and retreatments)

Outcome measures

Outcome measures
Measure	Drug: SOF/VEL for 6 Weeks n=74 Participants Open-label SOF/VEL 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the short treatment duration arm (A) for 6 weeks. SOF/VEL for 6 weeks: Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm A (6 weeks short treatment duration).	Drug: SOF/VEL for 12 Weeks n=77 Participants Open-label SOF/VEL 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the standard treatment duration arm (B) for 12 weeks. SOF/VEL for 12 weeks: Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm B (12 weeks standard treatment duration).
Number of Participants With Undetectable HCV RNA at 12 Weeks Post End of Treatment (SVR12) Following SOF/VEL for 6 Weeks as Compared With 12 Weeks in People With Recent HCV Infection- Among Per Protocol (PP) Population	69 Participants	77 Participants

Adverse Events

Drug: SOF/VEL for 6 Weeks

Serious events: 1 serious events

Other events: 34 other events

Deaths: 2 deaths

Drug: SOF/VEL for 12 Weeks

Serious events: 5 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Drug: SOF/VEL for 6 Weeks n=93 participants at risk Open-label SOF/VEL 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the short treatment duration arm (A) for 6 weeks. SOF/VEL for 6 weeks: Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm A (6 weeks short treatment duration).	Drug: SOF/VEL for 12 Weeks n=95 participants at risk Open-label SOF/VEL 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the standard treatment duration arm (B) for 12 weeks. SOF/VEL for 12 weeks: Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm B (12 weeks standard treatment duration).
General disorders Drug withdrawal syndrome	1.1% 1/93 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).	0.00% 0/95 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).
Injury, poisoning and procedural complications Contusion	0.00% 0/93 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).	1.1% 1/95 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).
Psychiatric disorders Opium addiction	0.00% 0/93 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).	1.1% 1/95 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/93 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).	1.1% 1/95 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).
Infections and infestations Pneumonia	0.00% 0/93 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).	1.1% 1/95 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).
Infections and infestations Cellulitis of leg	0.00% 0/93 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).	1.1% 1/95 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).

Other adverse events

Other adverse events
Measure	Drug: SOF/VEL for 6 Weeks n=93 participants at risk Open-label SOF/VEL 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the short treatment duration arm (A) for 6 weeks. SOF/VEL for 6 weeks: Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm A (6 weeks short treatment duration).	Drug: SOF/VEL for 12 Weeks n=95 participants at risk Open-label SOF/VEL 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the standard treatment duration arm (B) for 12 weeks. SOF/VEL for 12 weeks: Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm B (12 weeks standard treatment duration).
General disorders Fatigue	9.7% 9/93 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).	12.6% 12/95 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).
Nervous system disorders Headache	6.5% 6/93 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).	11.6% 11/95 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).
Infections and infestations Nasopharyngitis	8.6% 8/93 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).	9.5% 9/95 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).
Gastrointestinal disorders Nausea	5.4% 5/93 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).	9.5% 9/95 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).
Gastrointestinal disorders Diarrhoea	6.5% 6/93 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).	7.4% 7/95 • All adverse events up to 4 weeks after the last dose of study drug administration, an average of 10 weeks (arm A) and 16 weeks (arm B).

Additional Information

Pip Marks, Clinical Trials Manager

The Kirby Institute

Phone: +61 2 9385 0886

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place