Trial Outcomes & Findings for A Study to Assess the Efficacy and Safety of the Combination of Simeprevir and Daclatasvir in Chronic Hepatitis C Genotype 1b-Infected Participants (NCT NCT02268864)

NCT ID: NCT02268864

Last Updated: 2017-03-16

Results Overview

Participants were considered to have reached SVR12, if 12 weeks after the actual end of treatment (EOT), hepatitis C virus (HCV) ribonucleic acid (RNA) was less than lower limit of quantification (\<LLOQ) (detectable or undetectable).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 106 participants
• Primary outcome timeframe: At 12 weeks after end of treatment
• Results posted on: 2017-03-16

Participant Flow

Participant milestones

Measure	12 Weeks Prior Amendment Simeprevir 150 milligram (mg) once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who completed the 12-week treatment before Amendment 3 of the protocol was implemented.	12 Weeks Post Amendment Simeprevir 150 mg once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who opted for a 12-week treatment period after amendment.	24 Weeks Extension Simeprevir 150 mg once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who opted for an extended 24-week treatment after amendment.
Overall Study STARTED	17	25	64
Overall Study COMPLETED	15	24	64
Overall Study NOT COMPLETED	2	1	0

Reasons for withdrawal

Measure	12 Weeks Prior Amendment Simeprevir 150 milligram (mg) once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who completed the 12-week treatment before Amendment 3 of the protocol was implemented.	12 Weeks Post Amendment Simeprevir 150 mg once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who opted for a 12-week treatment period after amendment.	24 Weeks Extension Simeprevir 150 mg once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who opted for an extended 24-week treatment after amendment.
Overall Study Withdrawal by Subject	2	0	0
Overall Study Death	0	1	0

Baseline Characteristics

A Study to Assess the Efficacy and Safety of the Combination of Simeprevir and Daclatasvir in Chronic Hepatitis C Genotype 1b-Infected Participants

Baseline characteristics by cohort

Measure	12 Weeks Prior Amendment n=17 Participants Simeprevir 150 milligram (mg) once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who completed the 12-week treatment before Amendment 3 of the protocol was implemented.	12 Weeks Post Amendment n=25 Participants Simeprevir 150 mg once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who opted for a 12-week treatment period after amendment.	24 Weeks Extension n=64 Participants Simeprevir 150 mg once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who opted for an extended 24-week treatment after amendment.	Total n=106 Participants Total of all reporting groups
Age, Continuous	53.0 years FULL_RANGE 15.34 • n=5 Participants	64.0 years FULL_RANGE 14.77 • n=7 Participants	59.0 years FULL_RANGE 12.6 • n=5 Participants	59.0 years FULL_RANGE 13.53 • n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	11 Participants n=7 Participants	27 Participants n=5 Participants	43 Participants n=4 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	14 Participants n=7 Participants	37 Participants n=5 Participants	63 Participants n=4 Participants
Region of Enrollment Belgium	6 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	12 Participants n=4 Participants
Region of Enrollment France	3 Participants n=5 Participants	3 Participants n=7 Participants	19 Participants n=5 Participants	25 Participants n=4 Participants
Region of Enrollment Germany	3 Participants n=5 Participants	3 Participants n=7 Participants	14 Participants n=5 Participants	20 Participants n=4 Participants
Region of Enrollment Hungary	4 Participants n=5 Participants	0 Participants n=7 Participants	8 Participants n=5 Participants	12 Participants n=4 Participants
Region of Enrollment Italy	0 Participants n=5 Participants	10 Participants n=7 Participants	6 Participants n=5 Participants	16 Participants n=4 Participants
Region of Enrollment Spain	1 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants	20 Participants n=4 Participants
Region of Enrollment United Kingdom	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: At 12 weeks after end of treatment

Population: The intent-to-treat (ITT) analysis set is defined as all participants who received at least one dose of simeprevir or daclatasvir.

Participants were considered to have reached SVR12, if 12 weeks after the actual end of treatment (EOT), hepatitis C virus (HCV) ribonucleic acid (RNA) was less than lower limit of quantification (<LLOQ) (detectable or undetectable).

Outcome measures

Measure	12 Weeks Prior Amendment n=17 Participants Simeprevir 150 milligram (mg) once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who completed the 12-week treatment before Amendment 3 of the protocol was implemented.	12 Weeks Post Amendment n=25 Participants Simeprevir 150 mg once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who opted for a 12-week treatment period after amendment.	24 Weeks Extension n=64 Participants Simeprevir 150 mg once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who opted for an extended 24-week treatment after amendment.
Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)	70.6 percentage of participants Interval 44.04 to 89.69	100 percentage of participants Interval 86.28 to 100.0	93.8 percentage of participants Interval 84.76 to 98.27

SECONDARY outcome

Timeframe: At 4 weeks after actual EOT

Population: The ITT analysis set is defined as all participants who received at least one dose of simeprevir or daclatasvir.

Participants were considered to have reached SVR4, if 4 weeks after the actual EOT, HCV RNA was <LLOQ (detectable or undetectable).

Outcome measures

Measure	12 Weeks Prior Amendment n=17 Participants Simeprevir 150 milligram (mg) once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who completed the 12-week treatment before Amendment 3 of the protocol was implemented.	12 Weeks Post Amendment n=25 Participants Simeprevir 150 mg once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who opted for a 12-week treatment period after amendment.	24 Weeks Extension n=64 Participants Simeprevir 150 mg once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who opted for an extended 24-week treatment after amendment.
Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Study Drug Treatment (SVR4)	70.6 percentage of participants Interval 44.04 to 89.69	100 percentage of participants Interval 86.28 to 100.0	93.8 percentage of participants Interval 84.76 to 98.27

SECONDARY outcome

Timeframe: At 24 weeks after actual EOT

Population: The ITT analysis set is defined as all participants who received at least one dose of simeprevir or daclatasvir.

Participants were considered to have reached SVR24, if 24 weeks after the actual EOT, HCV RNA was <LLOQ (detectable or undetectable).

Outcome measures

Measure	12 Weeks Prior Amendment n=17 Participants Simeprevir 150 milligram (mg) once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who completed the 12-week treatment before Amendment 3 of the protocol was implemented.	12 Weeks Post Amendment n=25 Participants Simeprevir 150 mg once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who opted for a 12-week treatment period after amendment.	24 Weeks Extension n=64 Participants Simeprevir 150 mg once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who opted for an extended 24-week treatment after amendment.
Percentage of Participants With SVR 24 Weeks After End of Study Drug Treatment (SVR 24)	70.6 percentage of participants Interval 44.04 to 89.69	100 percentage of participants Interval 86.28 to 100.0	93.8 percentage of participants Interval 84.76 to 98.27

SECONDARY outcome

Timeframe: Up to Week 24 after actual EOT

Population: The ITT analysis set is defined as all participants who received at least one dose of simeprevir or daclatasvir.

Participants were considered on-treatment failures if they did not achieve SVR12 and had (confirmed) detectable HCV RNA, ie, <LLOQ detectable or greater than equal to (>=) LLOQ at EOT.

Outcome measures

Measure	12 Weeks Prior Amendment n=17 Participants Simeprevir 150 milligram (mg) once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who completed the 12-week treatment before Amendment 3 of the protocol was implemented.	12 Weeks Post Amendment n=25 Participants Simeprevir 150 mg once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who opted for a 12-week treatment period after amendment.	24 Weeks Extension n=64 Participants Simeprevir 150 mg once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who opted for an extended 24-week treatment after amendment.
Percentage of Participants With On-treatment Failure	29.4 percentage of participants	0.0 percentage of participants	4.7 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: The ITT analysis set is defined as all participants who received at least one dose of simeprevir or daclatasvir.

Participants were considered to have had viral breakthrough if they had a confirmed greater than (>) 1.0 log10 international units/milliliter (IU/mL) increase in HCV RNA from nadir OR confirmed HCV RNA >100 IU/mL while previously having achieved HCV RNA <LLOQ when on study treatment.

Outcome measures

Measure	12 Weeks Prior Amendment n=17 Participants Simeprevir 150 milligram (mg) once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who completed the 12-week treatment before Amendment 3 of the protocol was implemented.	12 Weeks Post Amendment n=25 Participants Simeprevir 150 mg once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who opted for a 12-week treatment period after amendment.	24 Weeks Extension n=64 Participants Simeprevir 150 mg once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who opted for an extended 24-week treatment after amendment.
Number of Participants With Viral Breakthrough	4 participants	0 participants	3 participants

SECONDARY outcome

Timeframe: Up to Week 24 after actual EOT

Population: The ITT analysis set is defined as all participants who received at least one dose of simeprevir or daclatasvir.

Participants were considered to have had viral relapse if they did not achieve SVR12 and met the following conditions: had HCV RNA <LLOQ (undetectable) at EOT and had HCV RNA >=LLOQ during the follow-up period.

Outcome measures

Measure	12 Weeks Prior Amendment n=17 Participants Simeprevir 150 milligram (mg) once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who completed the 12-week treatment before Amendment 3 of the protocol was implemented.	12 Weeks Post Amendment n=25 Participants Simeprevir 150 mg once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who opted for a 12-week treatment period after amendment.	24 Weeks Extension n=64 Participants Simeprevir 150 mg once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who opted for an extended 24-week treatment after amendment.
Number of Participants With Viral Relapse	0 participants	0 participants	1 participants

Adverse Events

1-12 Weeks

Serious events: 4 serious events

Other events: 44 other events

Deaths: 0 deaths

12-24 Weeks

Serious events: 3 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	1-12 Weeks n=106 participants at risk Simeprevir 150 mg once daily as an oral capsule in combination with Daclatasvir 60 mg once daily as an oral tablet for participants who has adverse events (AEs) that started before or on day 88 on treatment.	12-24 Weeks n=64 participants at risk Simeprevir 150 mg once daily as an oral capsule in combination with Daclatasvir 60 mg once daily as an oral tablet for participants who has AEs that started after day 88 on treatment.
Cardiac disorders Atrial Fibrillation	0.94% 1/106 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).	0.00% 0/64 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).
Cardiac disorders Pericarditis	0.00% 0/106 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).	1.6% 1/64 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).
Gastrointestinal disorders Abdominal Pain	0.94% 1/106 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).	0.00% 0/64 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).
Gastrointestinal disorders Vomiting	0.94% 1/106 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).	0.00% 0/64 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).
Hepatobiliary disorders Cholelithiasis	0.00% 0/106 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).	1.6% 1/64 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).
Injury, poisoning and procedural complications Fall	0.00% 0/106 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).	1.6% 1/64 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).
Injury, poisoning and procedural complications Wound Haemorrhage	0.00% 0/106 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).	1.6% 1/64 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).
Renal and urinary disorders Acute Kidney Injury	0.94% 1/106 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).	0.00% 0/64 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).
Skin and subcutaneous tissue disorders Photosensitivity Reaction	0.94% 1/106 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).	0.00% 0/64 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).

Other adverse events

Measure	1-12 Weeks n=106 participants at risk Simeprevir 150 mg once daily as an oral capsule in combination with Daclatasvir 60 mg once daily as an oral tablet for participants who has adverse events (AEs) that started before or on day 88 on treatment.	12-24 Weeks n=64 participants at risk Simeprevir 150 mg once daily as an oral capsule in combination with Daclatasvir 60 mg once daily as an oral tablet for participants who has AEs that started after day 88 on treatment.
General disorders Asthenia	13.2% 14/106 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).	1.6% 1/64 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).
General disorders Fatigue	15.1% 16/106 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).	1.6% 1/64 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).
Nervous system disorders Headache	15.1% 16/106 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).	0.00% 0/64 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).
Skin and subcutaneous tissue disorders Pruritus	10.4% 11/106 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).	0.00% 0/64 • Up to 24 weeks Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).

Additional Information

Trial Physician

Janssen Research and Developement, Belgium

Email: ClinicalTrialDisclosure@its.jnj.com

Results disclosure agreements

• Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, 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 by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
• Publication restrictions are in place

Restriction type: OTHER