Trial Outcomes & Findings for Efficacy and Safety of Alisporivir Triple Therapy in Chronic Hepatitis C Genotype 1 Treatment-naïve Participants (NCT NCT01318694)
NCT ID: NCT01318694
Last Updated: 2016-09-30
Results Overview
SVR12 was defined as hepatitis C virus (HCV) RNA laboratory value below the level of quantification (\< LOQ; i.e., 25 IU/ml) 12 weeks after the end of treatment.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1081 participants
Primary outcome timeframe
12 weeks after the end of treatment
Results posted on
2016-09-30
Participant Flow
Of the 1580 patients screened at multiple global sites, 1081 (68.4%) were randomized and 499 (31.6%) discontinued from the study prior to randomization.
Due to mis-randomization, four patients did not have a baseline visit and never started study medications. They were included in screened and randomized, but excluded from the Full Analysis Set and the Safety Set.
Participant milestones
| Measure |
Treatment Arm A
Alisporivir (ALV) 600 mg twice daily (BID) with Peginterferon alfa-2a (PEG) and ribavirin (RBV) for 1 week, followed by an additional 23 or 47 weeks according to response-guided treatment duration (RGT)
|
Treatment Arm B
Alisporivir (ALV) 400 mg twice daily (BID) with PEG and RBV for 24 or 48 weeks according to response-guided treatment duration (RGT)
|
Treatment Arm C
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg once daily (QD) for 47 weeks
|
Treatment Arm D
ALV Placebo with PEG and RBV for 48 weeks
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
275
|
270
|
268
|
268
|
|
Overall Study
Full Analysis Set
|
274
|
270
|
265
|
268
|
|
Overall Study
Safety Set
|
273
|
268
|
265
|
265
|
|
Overall Study
COMPLETED
|
223
|
212
|
225
|
200
|
|
Overall Study
NOT COMPLETED
|
52
|
58
|
43
|
68
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Efficacy and Safety of Alisporivir Triple Therapy in Chronic Hepatitis C Genotype 1 Treatment-naïve Participants
Baseline characteristics by cohort
| Measure |
Treatment Arm A
n=274 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT
|
Treatment Arm B
n=270 Participants
Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT
|
Treatment Arm C
n=265 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks
|
Treatment Arm D
n=268 Participants
ALV Placebo with PEG and RBV for 48 weeks
|
Total
n=1077 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
45.9 years
STANDARD_DEVIATION 11.08 • n=5 Participants
|
45.8 years
STANDARD_DEVIATION 11.95 • n=7 Participants
|
45.5 years
STANDARD_DEVIATION 12.15 • n=5 Participants
|
46.3 years
STANDARD_DEVIATION 11.53 • n=4 Participants
|
45.9 years
STANDARD_DEVIATION 11.67 • n=21 Participants
|
|
Sex: Female, Male
Female
|
113 Participants
n=5 Participants
|
106 Participants
n=7 Participants
|
134 Participants
n=5 Participants
|
114 Participants
n=4 Participants
|
467 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
161 Participants
n=5 Participants
|
164 Participants
n=7 Participants
|
131 Participants
n=5 Participants
|
154 Participants
n=4 Participants
|
610 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 12 weeks after the end of treatmentPopulation: Full Analysis Set
SVR12 was defined as hepatitis C virus (HCV) RNA laboratory value below the level of quantification (\< LOQ; i.e., 25 IU/ml) 12 weeks after the end of treatment.
Outcome measures
| Measure |
Treatment Arm A
n=274 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT
|
Treatment Arm B
n=270 Participants
Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT
|
Treatment Arm C
n=265 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks
|
Treatment Arm D
n=268 Participants
ALV Placebo with PEG and RBV for 48 weeks
|
|---|---|---|---|---|
|
Percentage of Participants Who Achieved Sustained Virologic Response (SVR) 12 Weeks After the End of Treatment (SVR12)
|
68.6 percentage of participants
|
68.9 percentage of participants
|
69.4 percentage of participants
|
52.5 percentage of participants
|
SECONDARY outcome
Timeframe: 24 weeks after the end of treatmentPopulation: Participants in the Full Analysis Set with available data
SVR24 was defined as HCV RNA laboratory value \< LOQ 24 weeks after the end of treatment.
Outcome measures
| Measure |
Treatment Arm A
n=273 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT
|
Treatment Arm B
n=268 Participants
Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT
|
Treatment Arm C
n=265 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks
|
Treatment Arm D
n=265 Participants
ALV Placebo with PEG and RBV for 48 weeks
|
|---|---|---|---|---|
|
Percentage of Participants Who Achieved SVR 24 Weeks After the End of Treatment (SVR24)
|
68.5 percentage of participants
|
69.0 percentage of participants
|
68.3 percentage of participants
|
51.7 percentage of participants
|
SECONDARY outcome
Timeframe: after 4 weeks of treatmentPopulation: Participants in the Full Analysis Set with available data
RVR4 was defined as serum HCV RNA \< LOQ after 4 weeks of treatment.
Outcome measures
| Measure |
Treatment Arm A
n=268 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT
|
Treatment Arm B
n=258 Participants
Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT
|
Treatment Arm C
n=258 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks
|
Treatment Arm D
n=261 Participants
ALV Placebo with PEG and RBV for 48 weeks
|
|---|---|---|---|---|
|
Percentage of Participants With Rapid Virologic Response (RVR) After 4 Weeks of Treatment (RVR4)
|
60.1 percentage of participants
|
72.5 percentage of participants
|
56.6 percentage of participants
|
28.4 percentage of participants
|
SECONDARY outcome
Timeframe: after 12 weeks of treatmentPopulation: Participants in the Full Analysis Set with available data
EVR was defined as a ≥ 2 log10 decrease in HCV RNA or HCV RNA \< LOQ after 12 weeks of treatment.
Outcome measures
| Measure |
Treatment Arm A
n=259 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT
|
Treatment Arm B
n=242 Participants
Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT
|
Treatment Arm C
n=247 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks
|
Treatment Arm D
n=256 Participants
ALV Placebo with PEG and RBV for 48 weeks
|
|---|---|---|---|---|
|
Percentage of Participants With Early Virologic Response (EVR) After 12 Weeks of Treatment
|
97.7 percentage of participants
|
98.3 percentage of participants
|
99.6 percentage of participants
|
89.8 percentage of participants
|
SECONDARY outcome
Timeframe: after 12 weeks of treatmentPopulation: Participants in the Full Analysis Set with available data
pEVR was defined as a ≥ 2 log10 decrease in HCV RNA and still detectable (≥ LOQ) after 12 weeks of treatment.
Outcome measures
| Measure |
Treatment Arm A
n=259 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT
|
Treatment Arm B
n=242 Participants
Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT
|
Treatment Arm C
n=247 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks
|
Treatment Arm D
n=256 Participants
ALV Placebo with PEG and RBV for 48 weeks
|
|---|---|---|---|---|
|
Percentage of Participants With Partial Early Virologic Response (pEVR) After 12 Weeks of Treatment
|
8.1 percentage of participants
|
2.1 percentage of participants
|
10.5 percentage of participants
|
19.5 percentage of participants
|
SECONDARY outcome
Timeframe: after 12 weeks of treatmentPopulation: Participants in the Full Analysis Set with available data
cEVR was defined as serum HCV RNA \< LOQ after 12 weeks of treatment.
Outcome measures
| Measure |
Treatment Arm A
n=259 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT
|
Treatment Arm B
n=242 Participants
Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT
|
Treatment Arm C
n=247 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks
|
Treatment Arm D
n=256 Participants
ALV Placebo with PEG and RBV for 48 weeks
|
|---|---|---|---|---|
|
Percentage of Participants With Complete Early Virologic Response (cEVR) After 12 Weeks of Treatment
|
89.6 percentage of participants
|
96.3 percentage of participants
|
89.1 percentage of participants
|
70.3 percentage of participants
|
SECONDARY outcome
Timeframe: from 4 to 12 weeks of treatmentPopulation: Participants in the Full Analysis Set with available data
eRVR was defined as achieving RVR4 and maintaining HCV RNA \< LOQ until Week 12.
Outcome measures
| Measure |
Treatment Arm A
n=259 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT
|
Treatment Arm B
n=242 Participants
Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT
|
Treatment Arm C
n=247 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks
|
Treatment Arm D
n=256 Participants
ALV Placebo with PEG and RBV for 48 weeks
|
|---|---|---|---|---|
|
Percentage of Participants With Extended Rapid Virologic Response (eRVR) From 4 to 12 Weeks of Treatment
|
60.2 percentage of participants
|
71.1 percentage of participants
|
56.7 percentage of participants
|
28.1 percentage of participants
|
SECONDARY outcome
Timeframe: at treatment end within 48 weeksPopulation: Participants in the Full Analysis Set with available data
ETR was defined as serum HCV RNA \< LOQ at treatment end (completed or prematurely discontinued).
Outcome measures
| Measure |
Treatment Arm A
n=271 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT
|
Treatment Arm B
n=268 Participants
Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT
|
Treatment Arm C
n=264 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks
|
Treatment Arm D
n=265 Participants
ALV Placebo with PEG and RBV for 48 weeks
|
|---|---|---|---|---|
|
Percentage of Participants With End of Treatment Response (ETR) at Treatment End Within 48 Weeks
|
88.2 percentage of participants
|
87.7 percentage of participants
|
87.5 percentage of participants
|
80.0 percentage of participants
|
SECONDARY outcome
Timeframe: within 48 weeksPopulation: Participants in the Safety Set, defined as having received at least one dose of study medication, with available data
ALT abnormalities were summarized as participants who had either: * ALT \> 2 x upper limit of normal (ULN) during the study and \> 2 x ULN at baseline * ALT \> 3 x ULN during the study and \> 2 x ULN at baseline
Outcome measures
| Measure |
Treatment Arm A
n=271 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT
|
Treatment Arm B
n=267 Participants
Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT
|
Treatment Arm C
n=264 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks
|
Treatment Arm D
n=264 Participants
ALV Placebo with PEG and RBV for 48 weeks
|
|---|---|---|---|---|
|
Percentage of Participants With Alanine Aminotransferase (ALT) Abnormalities Within 48 Weeks
> 2 x ULN and > 2 x baseline
|
1.5 percentage of participants
|
0.4 percentage of participants
|
1.9 percentage of participants
|
1.5 percentage of participants
|
|
Percentage of Participants With Alanine Aminotransferase (ALT) Abnormalities Within 48 Weeks
> 3 x ULN and > 2 x baseline
|
0.7 percentage of participants
|
0.0 percentage of participants
|
1.5 percentage of participants
|
0.8 percentage of participants
|
SECONDARY outcome
Timeframe: within 48 weeksPopulation: Participants in the Safety Set with available data
Grading was according to the Modified Division of Microbiology \& Infectious Diseases (DMID) Toxicity Tables (version 2.0). Participants with multiple abnormalities were counted only once in the worst category.
Outcome measures
| Measure |
Treatment Arm A
n=271 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT
|
Treatment Arm B
n=267 Participants
Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT
|
Treatment Arm C
n=264 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks
|
Treatment Arm D
n=264 Participants
ALV Placebo with PEG and RBV for 48 weeks
|
|---|---|---|---|---|
|
Percentage of Participants With Grade 3 or 4 Anemia During Treatment Within 48 Weeks
Grade 3
|
1.8 percentage of participants
|
3.4 percentage of participants
|
0.8 percentage of participants
|
1.9 percentage of participants
|
|
Percentage of Participants With Grade 3 or 4 Anemia During Treatment Within 48 Weeks
Grade 4
|
0.0 percentage of participants
|
0.4 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: within 48 weeksPopulation: Participants in the Safety Set with available data
Grading was according to the DMID Toxicity Tables (version 2.0). Participants with multiple abnormalities were counted only once in the worst category.
Outcome measures
| Measure |
Treatment Arm A
n=270 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT
|
Treatment Arm B
n=263 Participants
Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT
|
Treatment Arm C
n=264 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks
|
Treatment Arm D
n=264 Participants
ALV Placebo with PEG and RBV for 48 weeks
|
|---|---|---|---|---|
|
Percentage of Participants With Grade 3 or 4 Neutropenia During Treatment Within 48 Weeks
Grade 4
|
4.4 percentage of participants
|
8.0 percentage of participants
|
7.2 percentage of participants
|
2.7 percentage of participants
|
|
Percentage of Participants With Grade 3 or 4 Neutropenia During Treatment Within 48 Weeks
Grade 3
|
24.4 percentage of participants
|
24.7 percentage of participants
|
23.1 percentage of participants
|
12.9 percentage of participants
|
SECONDARY outcome
Timeframe: within 48 weeksPopulation: Participants in the Safety Set with available data
Grading was according to the DMID Toxicity Tables (version 2.0). Participants with multiple abnormalities were counted only once in the worst category.
Outcome measures
| Measure |
Treatment Arm A
n=270 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT
|
Treatment Arm B
n=265 Participants
Alisporivir (ALV) 400 mg BID with PEG and RBV for 24 or 48 weeks according to RGT
|
Treatment Arm C
n=264 Participants
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks
|
Treatment Arm D
n=264 Participants
ALV Placebo with PEG and RBV for 48 weeks
|
|---|---|---|---|---|
|
Percentage of Participants With Grade 3 or 4 Thrombocytopenia During Treatment Within 48 Weeks
Grade 4
|
0.0 percentage of participants
|
1.1 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Grade 3 or 4 Thrombocytopenia During Treatment Within 48 Weeks
Grade 3
|
6.7 percentage of participants
|
21.9 percentage of participants
|
12.5 percentage of participants
|
1.9 percentage of participants
|
Adverse Events
Treatment Arm A
Serious events: 24 serious events
Other events: 256 other events
Deaths: 0 deaths
Treatment Arm B
Serious events: 28 serious events
Other events: 261 other events
Deaths: 0 deaths
Treatment Arm C
Serious events: 21 serious events
Other events: 250 other events
Deaths: 0 deaths
Treatment Arm D
Serious events: 28 serious events
Other events: 242 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment Arm A
n=273 participants at risk
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT
|
Treatment Arm B
n=268 participants at risk
Alisporivir (ALV) 400 mg twice daily (BID) with PEG and RBV for 24 or 48 weeks according to response-guided treatment duration (RGT)
|
Treatment Arm C
n=265 participants at risk
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks
|
Treatment Arm D
n=265 participants at risk
ALV Placebo with PEG and RBV for 48 weeks
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Respiratory, thoracic and mediastinal disorders
Tonsillar hypertrophy
|
0.00%
0/273
|
0.00%
0/268
|
0.38%
1/265
|
0.00%
0/265
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/273
|
0.37%
1/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Reproductive system and breast disorders
Bartholinitis
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Reproductive system and breast disorders
Dysfunctional uterine bleeding
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Reproductive system and breast disorders
Ovarian disorder
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary fibrosis
|
0.00%
0/273
|
0.00%
0/268
|
0.75%
2/265
|
0.00%
0/265
|
|
Blood and lymphatic system disorders
Anaemia
|
0.73%
2/273
|
0.37%
1/268
|
0.00%
0/265
|
0.75%
2/265
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.73%
2/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/273
|
0.37%
1/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Blood and lymphatic system disorders
Spontaneous haematoma
|
0.00%
0/273
|
0.37%
1/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/273
|
0.00%
0/268
|
0.38%
1/265
|
0.38%
1/265
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/273
|
0.00%
0/268
|
0.38%
1/265
|
0.00%
0/265
|
|
Cardiac disorders
Hypertensive heart disease
|
0.00%
0/273
|
0.37%
1/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/273
|
0.00%
0/268
|
0.38%
1/265
|
0.38%
1/265
|
|
Ear and labyrinth disorders
Acute vestibular syndrome
|
0.00%
0/273
|
0.00%
0/268
|
0.38%
1/265
|
0.00%
0/265
|
|
Ear and labyrinth disorders
Deafness neurosensory
|
0.00%
0/273
|
0.00%
0/268
|
0.38%
1/265
|
0.00%
0/265
|
|
Endocrine disorders
Thyroiditis
|
0.00%
0/273
|
0.00%
0/268
|
0.75%
2/265
|
0.00%
0/265
|
|
Endocrine disorders
Autoimmune thyroiditis
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Endocrine disorders
Hyperthyroidism
|
0.00%
0/273
|
0.00%
0/268
|
0.38%
1/265
|
0.00%
0/265
|
|
Eye disorders
Dacryoadenitis acquired
|
0.00%
0/273
|
0.37%
1/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/273
|
1.1%
3/268
|
0.38%
1/265
|
0.38%
1/265
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/273
|
0.75%
2/268
|
0.00%
0/265
|
0.75%
2/265
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/273
|
0.75%
2/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Gastrointestinal disorders
Nausea
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Gastrointestinal disorders
Pancreatitis
|
0.37%
1/273
|
0.37%
1/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/273
|
0.37%
1/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Gastrointestinal disorders
Gastritis
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Gastrointestinal disorders
Haematemesis
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Gastrointestinal disorders
Haemorrhoidal haemorrhage
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/273
|
0.00%
0/268
|
0.38%
1/265
|
0.00%
0/265
|
|
General disorders
Pyrexia
|
0.37%
1/273
|
0.75%
2/268
|
0.00%
0/265
|
0.00%
0/265
|
|
General disorders
Drug interaction
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
General disorders
Fatigue
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
General disorders
Influenza like illness
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
General disorders
Lipogranuloma
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
General disorders
Multi-organ failure
|
0.00%
0/273
|
0.37%
1/268
|
0.00%
0/265
|
0.00%
0/265
|
|
General disorders
Non-cardiac chest pain
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
General disorders
Pain
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/273
|
0.37%
1/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/273
|
0.00%
0/268
|
0.38%
1/265
|
0.00%
0/265
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/273
|
0.00%
0/268
|
0.38%
1/265
|
0.00%
0/265
|
|
Hepatobiliary disorders
Hepatosplenomegaly
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Infections and infestations
Appendicitis
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.75%
2/265
|
|
Infections and infestations
Bronchitis
|
0.37%
1/273
|
0.75%
2/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Infections and infestations
Pneumonia
|
0.37%
1/273
|
0.37%
1/268
|
0.38%
1/265
|
0.00%
0/265
|
|
Infections and infestations
Urinary tract infection
|
0.73%
2/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/273
|
0.37%
1/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Infections and infestations
Cellulitis
|
0.00%
0/273
|
0.00%
0/268
|
0.38%
1/265
|
0.00%
0/265
|
|
Infections and infestations
Cervicitis
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Infections and infestations
Enterocolitis infectious
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Infections and infestations
Influenza
|
0.00%
0/273
|
0.00%
0/268
|
0.38%
1/265
|
0.00%
0/265
|
|
Infections and infestations
Lobar pneumonia
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Infections and infestations
Nasal abscess
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Infections and infestations
Pulmonary tuberculosis
|
0.00%
0/273
|
0.37%
1/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Infections and infestations
Salpingo-oophoritis
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Infections and infestations
Tooth abscess
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/273
|
0.00%
0/268
|
0.38%
1/265
|
0.00%
0/265
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/273
|
0.00%
0/268
|
0.38%
1/265
|
0.00%
0/265
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/273
|
0.37%
1/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/273
|
0.37%
1/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/273
|
0.00%
0/268
|
0.38%
1/265
|
0.00%
0/265
|
|
Metabolism and nutrition disorders
Type 2 diabetes mellitus
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Musculoskeletal and connective tissue disorders
Exostosis
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Craniopharyngioma
|
0.00%
0/273
|
0.37%
1/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leiomyosarcoma
|
0.00%
0/273
|
0.00%
0/268
|
0.38%
1/265
|
0.00%
0/265
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma
|
0.00%
0/273
|
0.37%
1/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic neoplasm
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pituitary tumour benign
|
0.00%
0/273
|
0.00%
0/268
|
0.38%
1/265
|
0.00%
0/265
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostatic adenoma
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of the cervix
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Nervous system disorders
Dizziness
|
0.00%
0/273
|
0.37%
1/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Nervous system disorders
Headache
|
0.00%
0/273
|
0.37%
1/268
|
0.38%
1/265
|
0.00%
0/265
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.37%
1/273
|
0.37%
1/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Nervous system disorders
Syncope
|
0.00%
0/273
|
0.37%
1/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Nervous system disorders
Hemiparesis
|
0.00%
0/273
|
0.00%
0/268
|
0.38%
1/265
|
0.00%
0/265
|
|
Nervous system disorders
Intraventricular haemorrhage
|
0.00%
0/273
|
0.37%
1/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/273
|
0.00%
0/268
|
0.38%
1/265
|
0.00%
0/265
|
|
Psychiatric disorders
Depression
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Psychiatric disorders
Mania
|
0.00%
0/273
|
0.37%
1/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/273
|
0.75%
2/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Psychiatric disorders
Major depression
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Psychiatric disorders
Schizophrenia, paranoid type
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Vascular disorders
Hypertensive crisis
|
0.00%
0/273
|
1.1%
3/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Vascular disorders
Hypertension
|
0.00%
0/273
|
0.37%
1/268
|
0.38%
1/265
|
0.00%
0/265
|
|
Vascular disorders
Aortic dissection
|
0.00%
0/273
|
0.00%
0/268
|
0.00%
0/265
|
0.38%
1/265
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/273
|
0.37%
1/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Vascular disorders
Hypotension
|
0.37%
1/273
|
0.00%
0/268
|
0.00%
0/265
|
0.00%
0/265
|
|
Vascular disorders
Vasculitis
|
0.00%
0/273
|
0.00%
0/268
|
0.38%
1/265
|
0.00%
0/265
|
Other adverse events
| Measure |
Treatment Arm A
n=273 participants at risk
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by an additional 23 or 47 weeks according to RGT
|
Treatment Arm B
n=268 participants at risk
Alisporivir (ALV) 400 mg twice daily (BID) with PEG and RBV for 24 or 48 weeks according to response-guided treatment duration (RGT)
|
Treatment Arm C
n=265 participants at risk
Alisporivir (ALV) 600 mg BID with PEG and RBV for 1 week, followed by 600 mg QD for 47 weeks
|
Treatment Arm D
n=265 participants at risk
ALV Placebo with PEG and RBV for 48 weeks
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
41.4%
113/273
|
46.3%
124/268
|
34.3%
91/265
|
33.2%
88/265
|
|
Blood and lymphatic system disorders
Leukopenia
|
17.6%
48/273
|
10.1%
27/268
|
18.1%
48/265
|
10.2%
27/265
|
|
Blood and lymphatic system disorders
Lymphopenia
|
5.5%
15/273
|
2.6%
7/268
|
6.0%
16/265
|
3.0%
8/265
|
|
Blood and lymphatic system disorders
Neutropenia
|
31.5%
86/273
|
29.9%
80/268
|
32.5%
86/265
|
25.3%
67/265
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
17.2%
47/273
|
27.2%
73/268
|
18.5%
49/265
|
6.0%
16/265
|
|
Endocrine disorders
Hypothyroidism
|
6.2%
17/273
|
8.2%
22/268
|
8.7%
23/265
|
4.5%
12/265
|
|
Eye disorders
Ocular icterus
|
4.0%
11/273
|
5.2%
14/268
|
1.9%
5/265
|
1.5%
4/265
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.6%
18/273
|
9.0%
24/268
|
8.3%
22/265
|
5.7%
15/265
|
|
Gastrointestinal disorders
Constipation
|
4.4%
12/273
|
6.3%
17/268
|
2.6%
7/265
|
4.5%
12/265
|
|
Gastrointestinal disorders
Diarrhoea
|
11.0%
30/273
|
10.1%
27/268
|
14.3%
38/265
|
14.0%
37/265
|
|
Gastrointestinal disorders
Dyspepsia
|
8.4%
23/273
|
6.3%
17/268
|
12.1%
32/265
|
6.8%
18/265
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
4.0%
11/273
|
3.4%
9/268
|
2.6%
7/265
|
5.7%
15/265
|
|
Gastrointestinal disorders
Nausea
|
24.2%
66/273
|
25.0%
67/268
|
23.4%
62/265
|
17.0%
45/265
|
|
Gastrointestinal disorders
Vomiting
|
9.5%
26/273
|
14.6%
39/268
|
10.9%
29/265
|
7.2%
19/265
|
|
General disorders
Asthenia
|
15.8%
43/273
|
17.2%
46/268
|
17.4%
46/265
|
18.1%
48/265
|
|
General disorders
Chills
|
8.4%
23/273
|
11.2%
30/268
|
12.5%
33/265
|
7.9%
21/265
|
|
General disorders
Fatigue
|
30.8%
84/273
|
36.9%
99/268
|
32.8%
87/265
|
32.5%
86/265
|
|
General disorders
Influenza like illness
|
20.5%
56/273
|
19.4%
52/268
|
14.3%
38/265
|
15.1%
40/265
|
|
General disorders
Injection site erythema
|
5.1%
14/273
|
3.7%
10/268
|
6.4%
17/265
|
3.0%
8/265
|
|
General disorders
Irritability
|
7.0%
19/273
|
6.0%
16/268
|
7.9%
21/265
|
8.3%
22/265
|
|
General disorders
Pyrexia
|
28.6%
78/273
|
34.7%
93/268
|
30.9%
82/265
|
27.9%
74/265
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
11.7%
32/273
|
22.8%
61/268
|
9.4%
25/265
|
0.75%
2/265
|
|
Hepatobiliary disorders
Jaundice
|
2.6%
7/273
|
7.5%
20/268
|
1.1%
3/265
|
0.38%
1/265
|
|
Infections and infestations
Nasopharyngitis
|
3.3%
9/273
|
3.4%
9/268
|
6.4%
17/265
|
4.5%
12/265
|
|
Infections and infestations
Upper respiratory tract infection
|
5.9%
16/273
|
1.9%
5/268
|
6.0%
16/265
|
4.9%
13/265
|
|
Infections and infestations
Urinary tract infection
|
4.0%
11/273
|
5.2%
14/268
|
4.2%
11/265
|
3.0%
8/265
|
|
Investigations
Weight decreased
|
8.8%
24/273
|
10.4%
28/268
|
9.8%
26/265
|
6.8%
18/265
|
|
Metabolism and nutrition disorders
Decreased appetite
|
22.3%
61/273
|
22.0%
59/268
|
21.9%
58/265
|
15.8%
42/265
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
4.0%
11/273
|
8.6%
23/268
|
8.3%
22/265
|
5.3%
14/265
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
13.9%
38/273
|
13.1%
35/268
|
14.7%
39/265
|
10.9%
29/265
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.6%
18/273
|
5.2%
14/268
|
5.7%
15/265
|
7.5%
20/265
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
2.9%
8/273
|
6.3%
17/268
|
2.6%
7/265
|
3.8%
10/265
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
21.6%
59/273
|
19.8%
53/268
|
21.1%
56/265
|
19.6%
52/265
|
|
Nervous system disorders
Dizziness
|
12.1%
33/273
|
12.7%
34/268
|
9.4%
25/265
|
11.3%
30/265
|
|
Nervous system disorders
Dysgeusia
|
5.1%
14/273
|
8.2%
22/268
|
4.9%
13/265
|
4.2%
11/265
|
|
Nervous system disorders
Headache
|
33.3%
91/273
|
35.1%
94/268
|
35.5%
94/265
|
30.2%
80/265
|
|
Psychiatric disorders
Anxiety
|
6.2%
17/273
|
7.5%
20/268
|
9.4%
25/265
|
10.9%
29/265
|
|
Psychiatric disorders
Depression
|
7.3%
20/273
|
10.8%
29/268
|
10.6%
28/265
|
8.7%
23/265
|
|
Psychiatric disorders
Insomnia
|
17.9%
49/273
|
22.8%
61/268
|
18.9%
50/265
|
22.6%
60/265
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
17.2%
47/273
|
20.1%
54/268
|
22.3%
59/265
|
20.0%
53/265
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
13.6%
37/273
|
9.7%
26/268
|
8.7%
23/265
|
9.8%
26/265
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
4.4%
12/273
|
9.3%
25/268
|
5.7%
15/265
|
3.8%
10/265
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.5%
15/273
|
4.9%
13/268
|
7.2%
19/265
|
4.2%
11/265
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
22.0%
60/273
|
16.8%
45/268
|
21.5%
57/265
|
17.7%
47/265
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
7.7%
21/273
|
8.6%
23/268
|
11.7%
31/265
|
8.3%
22/265
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
21.2%
58/273
|
20.5%
55/268
|
18.5%
49/265
|
20.4%
54/265
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.8%
46/273
|
14.9%
40/268
|
17.0%
45/265
|
17.0%
45/265
|
|
Vascular disorders
Hypertension
|
11.4%
31/273
|
18.7%
50/268
|
12.8%
34/265
|
2.6%
7/265
|
Additional Information
Vice President Clinical Research & Development
Debiopharm International S.A.
Phone: 4121 321 01 11
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER