Trial Outcomes & Findings for Efficacy and Safety of Combinations of AL-335, Odalasvir (ODV) and Simeprevir (SMV) in the Treatment of Chronic Hepatitis C Infection (NCT NCT02765490)
NCT ID: NCT02765490
Last Updated: 2019-11-20
Results Overview
The SVR 12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than (\<) lower limit of quantification (LLOQ; 15 international unit per milliliter \[IU/mL\]) detectable or undetectable 12 weeks after actual EOT.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
365 participants
Primary outcome timeframe
Week 12 (Follow-Up Phase)
Results posted on
2019-11-20
Participant Flow
Participant milestones
| Measure |
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 6 weeks.
|
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 8 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
183
|
182
|
|
Overall Study
COMPLETED
|
182
|
179
|
|
Overall Study
NOT COMPLETED
|
1
|
3
|
Reasons for withdrawal
| Measure |
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 6 weeks.
|
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 8 weeks.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
|
Overall Study
Other
|
0
|
1
|
|
Overall Study
Death
|
0
|
1
|
Baseline Characteristics
Efficacy and Safety of Combinations of AL-335, Odalasvir (ODV) and Simeprevir (SMV) in the Treatment of Chronic Hepatitis C Infection
Baseline characteristics by cohort
| Measure |
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks
n=183 Participants
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 6 weeks.
|
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks
n=182 Participants
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 8 weeks.
|
Total
n=365 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
48 years
n=5 Participants
|
49 years
n=7 Participants
|
49 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
88 Participants
n=5 Participants
|
94 Participants
n=7 Participants
|
182 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
95 Participants
n=5 Participants
|
88 Participants
n=7 Participants
|
183 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
9 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
161 Participants
n=5 Participants
|
153 Participants
n=7 Participants
|
314 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
46 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
81 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
33 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
63 Participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
15 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
27 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
58 Participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
24 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
32 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
|
Region of Enrollment
Singapore
|
6 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 12 (Follow-Up Phase)Population: Intent-To-Treat (ITT) population included all randomized participants who took at least 1 dose of the study drug \[that is AL-335, Odalasvir (ODV) or Simeprevir (SMV)\].
The SVR 12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than (\<) lower limit of quantification (LLOQ; 15 international unit per milliliter \[IU/mL\]) detectable or undetectable 12 weeks after actual EOT.
Outcome measures
| Measure |
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks
n=183 Participants
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 6 weeks.
|
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks
n=182 Participants
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 8 weeks.
|
|---|---|---|
|
Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12)
|
98.9 Percentage of Participants
Interval 96.1 to 99.9
|
97.8 Percentage of Participants
Interval 94.5 to 99.4
|
SECONDARY outcome
Timeframe: Week 24 (Follow-Up Phase)Population: ITT population included all randomized participants who took at least 1 dose of the study drug (i.e., AL-335, ODV or SMV). Last Observation Carried Forward (LOCF) method was used to impute the missing values.
The SVR24 was defined as HCV RNA \<LLOQ (detectable or undetectable) 24 weeks after End of Treatment (EOT).
Outcome measures
| Measure |
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks
n=183 Participants
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 6 weeks.
|
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks
n=182 Participants
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 8 weeks.
|
|---|---|---|
|
Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Treatment (SVR24)
|
98.9 Percentage of Participants
Interval 96.1 to 99.9
|
97.3 Percentage of Participants
Interval 93.7 to 99.1
|
SECONDARY outcome
Timeframe: End of Treatment up to Week 24 (Follow up phase)Population: ITT population included all randomized participants who took at least 1 dose of the study drug (i.e, AL-335, ODV or SMV).
Viral Relapse: Participants who did not achieve SVR12, with HCV RNA \<LLOQ at the EOT and confirmed HCV RNA greater than or equal to (\>=) LLOQ during follow-up.
Outcome measures
| Measure |
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks
n=183 Participants
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 6 weeks.
|
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks
n=182 Participants
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 8 weeks.
|
|---|---|---|
|
Number of Participants With Viral Relapse
|
1 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: Up to Week 24 (Follow-up Phase)Population: ITT population included all randomized participants who took at least 1 dose of the study drug (i.e, AL-335, ODV or SMV).
Late Viral Relapse: Participants who achieved SVR12 but had confirmed HCV RNA\>=LLOQ afterwards during follow-up.
Outcome measures
| Measure |
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks
n=183 Participants
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 6 weeks.
|
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks
n=182 Participants
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 8 weeks.
|
|---|---|---|
|
Number of Participants With Late Viral Relapse
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: EOT up to Week 12 (Follow up Phase)Population: ITT population included all randomized participants who took at least 1 dose of the study drug (i.e, AL-335, ODV or SMV).
On-treatment failure: Participants who did not achieve SVR12 and with confirmed HCV RNA\>=LLOQ at the End of Treatment (EOT).
Outcome measures
| Measure |
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks
n=183 Participants
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 6 weeks.
|
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks
n=182 Participants
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 8 weeks.
|
|---|---|---|
|
Percentage of Participants With On-treatment Failure
|
0 Percentage of Participants
|
0 Percentage of Participants
|
SECONDARY outcome
Timeframe: Week 4 (Follow-Up Phase)Population: ITT population included all randomized participants who took at least 1 dose of the study drug (i.e, AL-335, ODV or SMV).
The SVR 4 was defined as participants were considered to have reached SVR4, if 4 weeks after the actual EOT, HCV RNA was \<LLOQ (detectable or undetectable).
Outcome measures
| Measure |
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks
n=183 Participants
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 6 weeks.
|
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks
n=182 Participants
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 8 weeks.
|
|---|---|---|
|
Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Treatment (EOT)
|
99.5 Percentage of Participants
Interval 97.0 to 100.0
|
98.4 Percentage of Participants
Interval 95.3 to 99.7
|
Adverse Events
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks
Serious events: 7 serious events
Other events: 83 other events
Deaths: 0 deaths
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks
Serious events: 4 serious events
Other events: 85 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks
n=183 participants at risk
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 6 weeks.
|
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks
n=182 participants at risk
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 8 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Intestinal Obstruction
|
0.55%
1/183 • Screening up to Follow-up (Week 24)
|
0.00%
0/182 • Screening up to Follow-up (Week 24)
|
|
Gastrointestinal disorders
Intestinal Strangulation
|
0.55%
1/183 • Screening up to Follow-up (Week 24)
|
0.00%
0/182 • Screening up to Follow-up (Week 24)
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.55%
1/183 • Screening up to Follow-up (Week 24)
|
0.00%
0/182 • Screening up to Follow-up (Week 24)
|
|
Infections and infestations
Infective Keratitis
|
0.00%
0/183 • Screening up to Follow-up (Week 24)
|
0.55%
1/182 • Screening up to Follow-up (Week 24)
|
|
Infections and infestations
Lower Respiratory Tract Infection
|
0.00%
0/183 • Screening up to Follow-up (Week 24)
|
0.55%
1/182 • Screening up to Follow-up (Week 24)
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.55%
1/183 • Screening up to Follow-up (Week 24)
|
0.00%
0/182 • Screening up to Follow-up (Week 24)
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
0.55%
1/183 • Screening up to Follow-up (Week 24)
|
0.00%
0/182 • Screening up to Follow-up (Week 24)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign Breast Neoplasm
|
0.00%
0/183 • Screening up to Follow-up (Week 24)
|
0.55%
1/182 • Screening up to Follow-up (Week 24)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Glioblastoma
|
0.00%
0/183 • Screening up to Follow-up (Week 24)
|
0.55%
1/182 • Screening up to Follow-up (Week 24)
|
|
Nervous system disorders
Ivth Nerve Paresis
|
0.55%
1/183 • Screening up to Follow-up (Week 24)
|
0.00%
0/182 • Screening up to Follow-up (Week 24)
|
|
Nervous system disorders
Parkinsonism
|
0.55%
1/183 • Screening up to Follow-up (Week 24)
|
0.00%
0/182 • Screening up to Follow-up (Week 24)
|
|
Respiratory, thoracic and mediastinal disorders
Choking
|
0.55%
1/183 • Screening up to Follow-up (Week 24)
|
0.00%
0/182 • Screening up to Follow-up (Week 24)
|
|
Vascular disorders
Hypertension
|
0.55%
1/183 • Screening up to Follow-up (Week 24)
|
0.00%
0/182 • Screening up to Follow-up (Week 24)
|
Other adverse events
| Measure |
Arm A: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 6 Weeks
n=183 participants at risk
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 6 weeks.
|
Arm B: AL-335 800 mg+ODV 25 mg+SMV 75 mg qd for 8 Weeks
n=182 participants at risk
Participants received AL-335 800 milligram (mg) (2\*400) tablets, Odalasvir (ODV) 25 mg tablet, and Simeprevir (SMV) 75 mg capsule once daily (qd) orally in the morning for 8 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
3.8%
7/183 • Screening up to Follow-up (Week 24)
|
5.5%
10/182 • Screening up to Follow-up (Week 24)
|
|
Gastrointestinal disorders
Nausea
|
7.1%
13/183 • Screening up to Follow-up (Week 24)
|
2.7%
5/182 • Screening up to Follow-up (Week 24)
|
|
General disorders
Asthenia
|
6.0%
11/183 • Screening up to Follow-up (Week 24)
|
4.4%
8/182 • Screening up to Follow-up (Week 24)
|
|
General disorders
Fatigue
|
14.8%
27/183 • Screening up to Follow-up (Week 24)
|
11.5%
21/182 • Screening up to Follow-up (Week 24)
|
|
Infections and infestations
Viral Upper Respiratory Tract Infection
|
7.1%
13/183 • Screening up to Follow-up (Week 24)
|
10.4%
19/182 • Screening up to Follow-up (Week 24)
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
4.4%
8/183 • Screening up to Follow-up (Week 24)
|
6.6%
12/182 • Screening up to Follow-up (Week 24)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.5%
10/183 • Screening up to Follow-up (Week 24)
|
7.1%
13/182 • Screening up to Follow-up (Week 24)
|
|
Nervous system disorders
Headache
|
21.9%
40/183 • Screening up to Follow-up (Week 24)
|
22.0%
40/182 • Screening up to Follow-up (Week 24)
|
|
Psychiatric disorders
Insomnia
|
8.2%
15/183 • Screening up to Follow-up (Week 24)
|
8.2%
15/182 • Screening up to Follow-up (Week 24)
|
Additional Information
Trial Physician, Medical Department
Janssen Research & Development, LLC
Phone: 844-434-4210
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
- Publication restrictions are in place
Restriction type: OTHER