Trial Outcomes & Findings for Efficacy and Safety Study of Pegylated Interferon Lambda-1a With Ribavirin and Daclatasvir, to Treat naïve Subjects With Chronic HCV Genotypes 1, 2, 3, and 4 Who Are Co-infected With HIV (NCT NCT01866930)
NCT ID: NCT01866930
Last Updated: 2023-06-13
Results Overview
SVR12 was defined as HCV RNA less than lower limit of quantification (\< LLOQ) (25 IU/mL; target detected or not detected) at follow-up week 12.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
453 participants
Primary outcome timeframe
Follow-up week 12
Results posted on
2023-06-13
Participant Flow
A total of 453 participants were enrolled in the study. 300 participants were randomized and received treatment. 153 participants were not randomized to a treatment group due to Adverse Event (3), withdrawal of consent (13), loss to follow-up (4), administrative reasons per sponsor (5), no longer met study criteria (105), or other reasons (23).
Participant milestones
| Measure |
Cohort A: HCV GT-2 or GT-3
Participants with HCV (Genotype 2 or 3) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for 12 weeks, for a total treatment duration of 24 weeks. Participants received 180μg of Lambda via subcutaneous injection, once weekly, 800 mg/day Ribavirin tablets, orally, twice daily, for a planned duration of 24 weeks. Participants were administered 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants were followed up for a duration of 24 weeks after 24 weeks of treatment.
|
Cohort B: HCV GT-1 or GT-4
Participants with HCV (Genotype 1 or 4) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for either 12 or 36 weeks. Participants were administered 180μg of Lambda via subcutaneous injection, once weekly, for a maximum of 48 weeks; body weight stratified dose of Ribavirin tablets, orally, twice daily, for maximum duration of 48 weeks (\<75 kg, total dose was 1000 mg/day, weighing \>=75 kg, total dose was 1200 mg/day); and 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants who achieved an extended rapid virologic response (eRVR) during initial 12 weeks were treated with Lambda/RBV for 12 weeks for total of 24 weeks. Participants who did not achieve eRVR during initial 12 weeks were treated with Lambda/RBV for 36 weeks for total of 48 weeks. Participants were followed up for a duration of 24 weeks after 24 or 48 weeks of treatment.
|
|---|---|---|
|
Treatment Period
STARTED
|
104
|
196
|
|
Treatment Period
COMPLETED
|
95
|
161
|
|
Treatment Period
NOT COMPLETED
|
9
|
35
|
|
Follow-up Period
STARTED
|
102
|
185
|
|
Follow-up Period
COMPLETED
|
96
|
176
|
|
Follow-up Period
NOT COMPLETED
|
6
|
9
|
Reasons for withdrawal
| Measure |
Cohort A: HCV GT-2 or GT-3
Participants with HCV (Genotype 2 or 3) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for 12 weeks, for a total treatment duration of 24 weeks. Participants received 180μg of Lambda via subcutaneous injection, once weekly, 800 mg/day Ribavirin tablets, orally, twice daily, for a planned duration of 24 weeks. Participants were administered 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants were followed up for a duration of 24 weeks after 24 weeks of treatment.
|
Cohort B: HCV GT-1 or GT-4
Participants with HCV (Genotype 1 or 4) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for either 12 or 36 weeks. Participants were administered 180μg of Lambda via subcutaneous injection, once weekly, for a maximum of 48 weeks; body weight stratified dose of Ribavirin tablets, orally, twice daily, for maximum duration of 48 weeks (\<75 kg, total dose was 1000 mg/day, weighing \>=75 kg, total dose was 1200 mg/day); and 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants who achieved an extended rapid virologic response (eRVR) during initial 12 weeks were treated with Lambda/RBV for 12 weeks for total of 24 weeks. Participants who did not achieve eRVR during initial 12 weeks were treated with Lambda/RBV for 36 weeks for total of 48 weeks. Participants were followed up for a duration of 24 weeks after 24 or 48 weeks of treatment.
|
|---|---|---|
|
Treatment Period
Other
|
1
|
0
|
|
Treatment Period
Death
|
0
|
2
|
|
Treatment Period
Poor/non compliance
|
0
|
2
|
|
Treatment Period
No longer meets study criteria
|
0
|
1
|
|
Treatment Period
Withdrawal by Subject
|
2
|
8
|
|
Treatment Period
Lack of Efficacy
|
1
|
9
|
|
Treatment Period
Adverse Event
|
4
|
12
|
|
Treatment Period
Lost to Follow-up
|
1
|
1
|
|
Follow-up Period
Lost to Follow-up
|
1
|
1
|
|
Follow-up Period
Other
|
1
|
5
|
|
Follow-up Period
No longer required per protocol
|
1
|
0
|
|
Follow-up Period
Withdrawal by Subject
|
3
|
3
|
Baseline Characteristics
Efficacy and Safety Study of Pegylated Interferon Lambda-1a With Ribavirin and Daclatasvir, to Treat naïve Subjects With Chronic HCV Genotypes 1, 2, 3, and 4 Who Are Co-infected With HIV
Baseline characteristics by cohort
| Measure |
Cohort A: HCV GT-2 or GT-3
n=104 Participants
Participants with HCV (Genotype 2 or 3) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for 12 weeks, for a total treatment duration of 24 weeks. Participants received 180μg of Lambda via subcutaneous injection, once weekly, 800 mg/day Ribavirin tablets, orally, twice daily, for a planned duration of 24 weeks. Participants were administered 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants were followed up for a duration of 24 weeks after 24 weeks of treatment.
|
Cohort B: HCV GT-1 or GT-4
n=196 Participants
Participants with HCV (Genotype 1 or 4) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for either 12 or 36 weeks. Participants were administered 180μg of Lambda via subcutaneous injection, once weekly, for a maximum of 48 weeks; body weight stratified dose of Ribavirin tablets, orally, twice daily, for maximum duration of 48 weeks (\<75 kg, total dose was 1000 mg/day, weighing \>=75 kg, total dose was 1200 mg/day); and 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants who achieved an extended rapid virologic response (eRVR) during initial 12 weeks were treated with Lambda/RBV for 12 weeks for total of 24 weeks. Participants who did not achieve eRVR during initial 12 weeks were treated with Lambda/RBV for 36 weeks for total of 48 weeks. Participants were followed up for a duration of 24 weeks after 24 or 48 weeks of treatment.
|
Total
n=300 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
43.7 years
STANDARD_DEVIATION 8.88 • n=5 Participants
|
46.6 years
STANDARD_DEVIATION 7.76 • n=7 Participants
|
45.6 years
STANDARD_DEVIATION 8.27 • n=5 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
68 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
76 Participants
n=5 Participants
|
156 Participants
n=7 Participants
|
232 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
10 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
41 Participants
n=5 Participants
|
79 Participants
n=7 Participants
|
120 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
53 Participants
n=5 Participants
|
106 Participants
n=7 Participants
|
159 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
93 Participants
n=5 Participants
|
171 Participants
n=7 Participants
|
264 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
HCV Genotype
HCV GT-1
|
0 Participants
n=5 Participants
|
149 Participants
n=7 Participants
|
149 Participants
n=5 Participants
|
|
HCV Genotype
HCV GT-2
|
20 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
HCV Genotype
HCV GT-3
|
83 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
83 Participants
n=5 Participants
|
|
HCV Genotype
HCV GT-4
|
0 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
|
HCV Genotype
Unknown
|
1 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Follow-up week 12Population: The analysis was performed in all treated subjects using modified intent-to-treat algorithm, where the numerator is based on subjects meeting the response criteria and the denominator is based on all treated subjects (Non-completer = Failure).
SVR12 was defined as HCV RNA less than lower limit of quantification (\< LLOQ) (25 IU/mL; target detected or not detected) at follow-up week 12.
Outcome measures
| Measure |
Cohort A: HCV GT-2 or GT-3
n=104 Participants
Participants with HCV (Genotype 2 or 3) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for 12 weeks, for a total treatment duration of 24 weeks. Participants received 180μg of Lambda via subcutaneous injection, once weekly, 800 mg/day Ribavirin tablets, orally, twice daily, for a planned duration of 24 weeks. Participants were administered 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants were followed up for a duration of 24 weeks after 24 weeks of treatment.
|
Cohort B: HCV GT-1 or GT-4
n=196 Participants
Participants with HCV (Genotype 1 or 4) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for either 12 or 36 weeks. Participants were administered 180μg of Lambda via subcutaneous injection, once weekly, for a maximum of 48 weeks; body weight stratified dose of Ribavirin tablets, orally, twice daily, for maximum duration of 48 weeks (\<75 kg, total dose was 1000 mg/day, weighing \>=75 kg, total dose was 1200 mg/day); and 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants who achieved an extended rapid virologic response (eRVR) during initial 12 weeks were treated with Lambda/RBV for 12 weeks for total of 24 weeks. Participants who did not achieve eRVR during initial 12 weeks were treated with Lambda/RBV for 36 weeks for total of 48 weeks. Participants were followed up for a duration of 24 weeks after 24 or 48 weeks of treatment.
|
|---|---|---|
|
Number of Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12)
|
88 Participants
|
149 Participants
|
SECONDARY outcome
Timeframe: Treatment weeks 4 and 12Population: The analysis was performed in all treated subjects using modified intent-to-treat algorithm, where the numerator is based on subjects meeting the response criteria and the denominator is based on all treated subjects (Non-completer = Failure).
RVR is defined as HCV RNA \< LLOQ target not detected at Week 4 and eRVR defined as HCV RNA \< LLOQ target not detected at Weeks 4 and 12
Outcome measures
| Measure |
Cohort A: HCV GT-2 or GT-3
n=104 Participants
Participants with HCV (Genotype 2 or 3) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for 12 weeks, for a total treatment duration of 24 weeks. Participants received 180μg of Lambda via subcutaneous injection, once weekly, 800 mg/day Ribavirin tablets, orally, twice daily, for a planned duration of 24 weeks. Participants were administered 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants were followed up for a duration of 24 weeks after 24 weeks of treatment.
|
Cohort B: HCV GT-1 or GT-4
n=196 Participants
Participants with HCV (Genotype 1 or 4) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for either 12 or 36 weeks. Participants were administered 180μg of Lambda via subcutaneous injection, once weekly, for a maximum of 48 weeks; body weight stratified dose of Ribavirin tablets, orally, twice daily, for maximum duration of 48 weeks (\<75 kg, total dose was 1000 mg/day, weighing \>=75 kg, total dose was 1200 mg/day); and 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants who achieved an extended rapid virologic response (eRVR) during initial 12 weeks were treated with Lambda/RBV for 12 weeks for total of 24 weeks. Participants who did not achieve eRVR during initial 12 weeks were treated with Lambda/RBV for 36 weeks for total of 48 weeks. Participants were followed up for a duration of 24 weeks after 24 or 48 weeks of treatment.
|
|---|---|---|
|
Number of Participants With Rapid Virologic Response (RVR) and Extended Rapid Virologic Response (eRVR)
RVR
|
82 Participants
|
149 Participants
|
|
Number of Participants With Rapid Virologic Response (RVR) and Extended Rapid Virologic Response (eRVR)
eRVR
|
80 Participants
|
138 Participants
|
SECONDARY outcome
Timeframe: Follow-up week 24Population: The analysis was performed in all treated subjects using modified intent-to-treat algorithm (numerator is based on subjects meeting the response criteria and the denominator is based on all treated subjects (Non-completer = Failure). Data was not collected for any participants due to termination of the study.
SVR24 was defined as HCV RNA \< LLOQ (25 IU/mL; target detected or not detected) at 24 weeks post treatment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: After Day 1 to end of treatment; up to Weeks 24 or 48Population: Analysis was performed in all treated participants.
All treated participants were monitored for treatment emergent cytopenic abnormalities (anemia as defined by hemoglobin (Hb) \< 10 g/dL, and/or neutropenia as defined by absolute neutrophil count (ANC) \< 750 mm3 and/or thrombocytopenia as defined by platelets \< 50,000/mm3) during the treatment period (Weeks 1, 2, 4, 6, 8, 12, 20, and 24, and at Weeks 28, 32, 36, 40, 44, and 48 for subjects requiring those visits).
Outcome measures
| Measure |
Cohort A: HCV GT-2 or GT-3
n=104 Participants
Participants with HCV (Genotype 2 or 3) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for 12 weeks, for a total treatment duration of 24 weeks. Participants received 180μg of Lambda via subcutaneous injection, once weekly, 800 mg/day Ribavirin tablets, orally, twice daily, for a planned duration of 24 weeks. Participants were administered 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants were followed up for a duration of 24 weeks after 24 weeks of treatment.
|
Cohort B: HCV GT-1 or GT-4
n=196 Participants
Participants with HCV (Genotype 1 or 4) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for either 12 or 36 weeks. Participants were administered 180μg of Lambda via subcutaneous injection, once weekly, for a maximum of 48 weeks; body weight stratified dose of Ribavirin tablets, orally, twice daily, for maximum duration of 48 weeks (\<75 kg, total dose was 1000 mg/day, weighing \>=75 kg, total dose was 1200 mg/day); and 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants who achieved an extended rapid virologic response (eRVR) during initial 12 weeks were treated with Lambda/RBV for 12 weeks for total of 24 weeks. Participants who did not achieve eRVR during initial 12 weeks were treated with Lambda/RBV for 36 weeks for total of 48 weeks. Participants were followed up for a duration of 24 weeks after 24 or 48 weeks of treatment.
|
|---|---|---|
|
Number of Participants With Treatment Emergent Cytopenic Abnormalities
|
4 Participants
|
15 Participants
|
SECONDARY outcome
Timeframe: After Day 1 to end of treatment; up to Weeks 24 or 48Population: Analysis was performed in all treated participants.
All treated participants were monitored for IFN-associated Flu-like and Musculoskeletal symptoms. Flu-like symptoms were defined as pyrexia, chills, or pain. Musculoskeletal symptoms were defined as arthralgia, myalgia, or back pain. Subjects were monitored throughout the treatment period during the treatment period (After day 1 up to week 24, or After day 1 up to week 48 for subjects requiring those visits).
Outcome measures
| Measure |
Cohort A: HCV GT-2 or GT-3
n=104 Participants
Participants with HCV (Genotype 2 or 3) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for 12 weeks, for a total treatment duration of 24 weeks. Participants received 180μg of Lambda via subcutaneous injection, once weekly, 800 mg/day Ribavirin tablets, orally, twice daily, for a planned duration of 24 weeks. Participants were administered 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants were followed up for a duration of 24 weeks after 24 weeks of treatment.
|
Cohort B: HCV GT-1 or GT-4
n=196 Participants
Participants with HCV (Genotype 1 or 4) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for either 12 or 36 weeks. Participants were administered 180μg of Lambda via subcutaneous injection, once weekly, for a maximum of 48 weeks; body weight stratified dose of Ribavirin tablets, orally, twice daily, for maximum duration of 48 weeks (\<75 kg, total dose was 1000 mg/day, weighing \>=75 kg, total dose was 1200 mg/day); and 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants who achieved an extended rapid virologic response (eRVR) during initial 12 weeks were treated with Lambda/RBV for 12 weeks for total of 24 weeks. Participants who did not achieve eRVR during initial 12 weeks were treated with Lambda/RBV for 36 weeks for total of 48 weeks. Participants were followed up for a duration of 24 weeks after 24 or 48 weeks of treatment.
|
|---|---|---|
|
Number of Participants With On-treatment IFN-associated Flu-like or Musculoskeletal Symptoms
Musculoskeletal symptoms
|
6 Participants
|
21 Participants
|
|
Number of Participants With On-treatment IFN-associated Flu-like or Musculoskeletal Symptoms
Flu-like symptoms
|
6 Participants
|
19 Participants
|
SECONDARY outcome
Timeframe: After Day 1 to end of treatment; up to Weeks 24 or 48Population: The analysis included all treated subjects up to the end of the treatment period (Day 1 to week 24, or Day 1 to week 48 for subjects requiring those visits).
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that. at any dose, results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug.
Outcome measures
| Measure |
Cohort A: HCV GT-2 or GT-3
n=104 Participants
Participants with HCV (Genotype 2 or 3) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for 12 weeks, for a total treatment duration of 24 weeks. Participants received 180μg of Lambda via subcutaneous injection, once weekly, 800 mg/day Ribavirin tablets, orally, twice daily, for a planned duration of 24 weeks. Participants were administered 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants were followed up for a duration of 24 weeks after 24 weeks of treatment.
|
Cohort B: HCV GT-1 or GT-4
n=196 Participants
Participants with HCV (Genotype 1 or 4) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for either 12 or 36 weeks. Participants were administered 180μg of Lambda via subcutaneous injection, once weekly, for a maximum of 48 weeks; body weight stratified dose of Ribavirin tablets, orally, twice daily, for maximum duration of 48 weeks (\<75 kg, total dose was 1000 mg/day, weighing \>=75 kg, total dose was 1200 mg/day); and 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants who achieved an extended rapid virologic response (eRVR) during initial 12 weeks were treated with Lambda/RBV for 12 weeks for total of 24 weeks. Participants who did not achieve eRVR during initial 12 weeks were treated with Lambda/RBV for 36 weeks for total of 48 weeks. Participants were followed up for a duration of 24 weeks after 24 or 48 weeks of treatment.
|
|---|---|---|
|
Number of Participants Who Died or Experienced Severe Adverse Events (SAEs), Dose Reductions of Lambda or Discontinuation Due to Adverse Events (AEs)
Deaths
|
0 Participants
|
3 Participants
|
|
Number of Participants Who Died or Experienced Severe Adverse Events (SAEs), Dose Reductions of Lambda or Discontinuation Due to Adverse Events (AEs)
SAEs
|
6 Participants
|
12 Participants
|
|
Number of Participants Who Died or Experienced Severe Adverse Events (SAEs), Dose Reductions of Lambda or Discontinuation Due to Adverse Events (AEs)
Lambda Dose Reduction
|
4 Participants
|
19 Participants
|
|
Number of Participants Who Died or Experienced Severe Adverse Events (SAEs), Dose Reductions of Lambda or Discontinuation Due to Adverse Events (AEs)
Discontinuation due to AEs
|
4 Participants
|
13 Participants
|
SECONDARY outcome
Timeframe: After Day 1 to end of treatment; up to Weeks 24 or 48Population: The analysis included all treated subjects up to the end of the treatment period (Day 1 to week 24, or Day 1 to week 48 for subjects requiring those visits).
Grade 3/4 treatment-emergent lab abnormalities that occurred in \>=5% of subjects in either cohort are reported. The analysis included all treated subjects up to the end of the treatment period (Day 1 to week 24, or Day 1 to week 48 for subjects requiring those visits). Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. AST = Aspartate aminotransferase, ALT = Alanine aminotransferase.
Outcome measures
| Measure |
Cohort A: HCV GT-2 or GT-3
n=104 Participants
Participants with HCV (Genotype 2 or 3) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for 12 weeks, for a total treatment duration of 24 weeks. Participants received 180μg of Lambda via subcutaneous injection, once weekly, 800 mg/day Ribavirin tablets, orally, twice daily, for a planned duration of 24 weeks. Participants were administered 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants were followed up for a duration of 24 weeks after 24 weeks of treatment.
|
Cohort B: HCV GT-1 or GT-4
n=196 Participants
Participants with HCV (Genotype 1 or 4) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for either 12 or 36 weeks. Participants were administered 180μg of Lambda via subcutaneous injection, once weekly, for a maximum of 48 weeks; body weight stratified dose of Ribavirin tablets, orally, twice daily, for maximum duration of 48 weeks (\<75 kg, total dose was 1000 mg/day, weighing \>=75 kg, total dose was 1200 mg/day); and 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants who achieved an extended rapid virologic response (eRVR) during initial 12 weeks were treated with Lambda/RBV for 12 weeks for total of 24 weeks. Participants who did not achieve eRVR during initial 12 weeks were treated with Lambda/RBV for 36 weeks for total of 48 weeks. Participants were followed up for a duration of 24 weeks after 24 or 48 weeks of treatment.
|
|---|---|---|
|
Number of Participants With Treatment-emergent Grade 3/4 Lab Abnormalities
Total Bilirubin
|
26 Participants
|
63 Participants
|
|
Number of Participants With Treatment-emergent Grade 3/4 Lab Abnormalities
AST
|
10 Participants
|
13 Participants
|
|
Number of Participants With Treatment-emergent Grade 3/4 Lab Abnormalities
ALT
|
2 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: Day 1 to end of treatment; up to week 24 or week 48Population: The analysis was performed in all evaluable treated participants.
All treated participants were monitored for change in Absolute CD4 T Lymphocyte count from Baseline to the end of the treatment period. The mean change in each arm for all evaluable participants is reported in Cells/µL.
Outcome measures
| Measure |
Cohort A: HCV GT-2 or GT-3
n=104 Participants
Participants with HCV (Genotype 2 or 3) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for 12 weeks, for a total treatment duration of 24 weeks. Participants received 180μg of Lambda via subcutaneous injection, once weekly, 800 mg/day Ribavirin tablets, orally, twice daily, for a planned duration of 24 weeks. Participants were administered 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants were followed up for a duration of 24 weeks after 24 weeks of treatment.
|
Cohort B: HCV GT-1 or GT-4
n=196 Participants
Participants with HCV (Genotype 1 or 4) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for either 12 or 36 weeks. Participants were administered 180μg of Lambda via subcutaneous injection, once weekly, for a maximum of 48 weeks; body weight stratified dose of Ribavirin tablets, orally, twice daily, for maximum duration of 48 weeks (\<75 kg, total dose was 1000 mg/day, weighing \>=75 kg, total dose was 1200 mg/day); and 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants who achieved an extended rapid virologic response (eRVR) during initial 12 weeks were treated with Lambda/RBV for 12 weeks for total of 24 weeks. Participants who did not achieve eRVR during initial 12 weeks were treated with Lambda/RBV for 36 weeks for total of 48 weeks. Participants were followed up for a duration of 24 weeks after 24 or 48 weeks of treatment.
|
|---|---|---|
|
Mean Change in Absolute CD4 T Lymphocyte Count From Baseline to End of Treatment
|
-42.4 Cells/uL
Interval -85.86 to 1.09
|
-104.9 Cells/uL
Interval -128.74 to -81.04
|
SECONDARY outcome
Timeframe: Day 1 to end of treatment; up to week 24 or week 48Population: The analysis was performed in all evaluable treated participants.
All treated participants were monitored for percent change in CD4 T Lymphocyte count from Baseline to the end of the treatment period. The mean percent change in each arm is presented for all evaluable participants.
Outcome measures
| Measure |
Cohort A: HCV GT-2 or GT-3
n=104 Participants
Participants with HCV (Genotype 2 or 3) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for 12 weeks, for a total treatment duration of 24 weeks. Participants received 180μg of Lambda via subcutaneous injection, once weekly, 800 mg/day Ribavirin tablets, orally, twice daily, for a planned duration of 24 weeks. Participants were administered 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants were followed up for a duration of 24 weeks after 24 weeks of treatment.
|
Cohort B: HCV GT-1 or GT-4
n=196 Participants
Participants with HCV (Genotype 1 or 4) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for either 12 or 36 weeks. Participants were administered 180μg of Lambda via subcutaneous injection, once weekly, for a maximum of 48 weeks; body weight stratified dose of Ribavirin tablets, orally, twice daily, for maximum duration of 48 weeks (\<75 kg, total dose was 1000 mg/day, weighing \>=75 kg, total dose was 1200 mg/day); and 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants who achieved an extended rapid virologic response (eRVR) during initial 12 weeks were treated with Lambda/RBV for 12 weeks for total of 24 weeks. Participants who did not achieve eRVR during initial 12 weeks were treated with Lambda/RBV for 36 weeks for total of 48 weeks. Participants were followed up for a duration of 24 weeks after 24 or 48 weeks of treatment.
|
|---|---|---|
|
Mean Percent Change in Absolute CD4 T Lymphocyte Count From Baseline to End of Treatment
|
-4.0 Percent change
Interval -10.32 to 2.24
|
-13.4 Percent change
Interval -18.91 to -7.98
|
SECONDARY outcome
Timeframe: Day 1 to end of treatment; up to week 24 or week 48Population: The analysis was performed in all evaluable treated participants.
All treated participants were monitored for change in Total Lymphocyte Count from Baseline to the end of the treatment period. The mean change in each arm for all evaluable participants is reported in Cells/µL.
Outcome measures
| Measure |
Cohort A: HCV GT-2 or GT-3
n=104 Participants
Participants with HCV (Genotype 2 or 3) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for 12 weeks, for a total treatment duration of 24 weeks. Participants received 180μg of Lambda via subcutaneous injection, once weekly, 800 mg/day Ribavirin tablets, orally, twice daily, for a planned duration of 24 weeks. Participants were administered 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants were followed up for a duration of 24 weeks after 24 weeks of treatment.
|
Cohort B: HCV GT-1 or GT-4
n=196 Participants
Participants with HCV (Genotype 1 or 4) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for either 12 or 36 weeks. Participants were administered 180μg of Lambda via subcutaneous injection, once weekly, for a maximum of 48 weeks; body weight stratified dose of Ribavirin tablets, orally, twice daily, for maximum duration of 48 weeks (\<75 kg, total dose was 1000 mg/day, weighing \>=75 kg, total dose was 1200 mg/day); and 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants who achieved an extended rapid virologic response (eRVR) during initial 12 weeks were treated with Lambda/RBV for 12 weeks for total of 24 weeks. Participants who did not achieve eRVR during initial 12 weeks were treated with Lambda/RBV for 36 weeks for total of 48 weeks. Participants were followed up for a duration of 24 weeks after 24 or 48 weeks of treatment.
|
|---|---|---|
|
Mean Change in Total Lymphocyte Count From Baseline to End of Treatment
|
-0.38 Cells/µL
Interval -0.5 to -0.25
|
-0.50 Cells/µL
Interval -0.56 to -0.43
|
SECONDARY outcome
Timeframe: Day 1 to end of treatment; up to week 24 or week 48Population: The analysis was performed in all evaluable treated participants.
All treated participants were monitored for percent change in Total Lymphocyte Count from Baseline to the end of the treatment period. The mean percent change in each arm is presented for all evaluable participants.
Outcome measures
| Measure |
Cohort A: HCV GT-2 or GT-3
n=104 Participants
Participants with HCV (Genotype 2 or 3) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for 12 weeks, for a total treatment duration of 24 weeks. Participants received 180μg of Lambda via subcutaneous injection, once weekly, 800 mg/day Ribavirin tablets, orally, twice daily, for a planned duration of 24 weeks. Participants were administered 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants were followed up for a duration of 24 weeks after 24 weeks of treatment.
|
Cohort B: HCV GT-1 or GT-4
n=196 Participants
Participants with HCV (Genotype 1 or 4) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for either 12 or 36 weeks. Participants were administered 180μg of Lambda via subcutaneous injection, once weekly, for a maximum of 48 weeks; body weight stratified dose of Ribavirin tablets, orally, twice daily, for maximum duration of 48 weeks (\<75 kg, total dose was 1000 mg/day, weighing \>=75 kg, total dose was 1200 mg/day); and 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants who achieved an extended rapid virologic response (eRVR) during initial 12 weeks were treated with Lambda/RBV for 12 weeks for total of 24 weeks. Participants who did not achieve eRVR during initial 12 weeks were treated with Lambda/RBV for 36 weeks for total of 48 weeks. Participants were followed up for a duration of 24 weeks after 24 or 48 weeks of treatment.
|
|---|---|---|
|
Mean Percent Change in Total Lymphocyte Count From Baseline to End of Treatment
|
-15.33 Percent change
Interval -20.46 to -10.19
|
-22.95 Percent change
Interval -26.04 to -19.86
|
SECONDARY outcome
Timeframe: Day 1 to end of treatment; up to week 24 or week 48Population: The analysis was performed in all evaluable treated participants.
All treated participants were monitored for change in Platelet Count from Baseline to the end of the treatment period. The mean change in each arm for all evaluable participants (units of measurement = x10\^9 cells/L).
Outcome measures
| Measure |
Cohort A: HCV GT-2 or GT-3
n=104 Participants
Participants with HCV (Genotype 2 or 3) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for 12 weeks, for a total treatment duration of 24 weeks. Participants received 180μg of Lambda via subcutaneous injection, once weekly, 800 mg/day Ribavirin tablets, orally, twice daily, for a planned duration of 24 weeks. Participants were administered 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants were followed up for a duration of 24 weeks after 24 weeks of treatment.
|
Cohort B: HCV GT-1 or GT-4
n=196 Participants
Participants with HCV (Genotype 1 or 4) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for either 12 or 36 weeks. Participants were administered 180μg of Lambda via subcutaneous injection, once weekly, for a maximum of 48 weeks; body weight stratified dose of Ribavirin tablets, orally, twice daily, for maximum duration of 48 weeks (\<75 kg, total dose was 1000 mg/day, weighing \>=75 kg, total dose was 1200 mg/day); and 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants who achieved an extended rapid virologic response (eRVR) during initial 12 weeks were treated with Lambda/RBV for 12 weeks for total of 24 weeks. Participants who did not achieve eRVR during initial 12 weeks were treated with Lambda/RBV for 36 weeks for total of 48 weeks. Participants were followed up for a duration of 24 weeks after 24 or 48 weeks of treatment.
|
|---|---|---|
|
Mean Change in Platelet Count From Baseline to End of Treatment
|
32.7 10^9 cells/L
Interval 24.62 to 40.84
|
33.3 10^9 cells/L
Interval 27.1 to 39.57
|
SECONDARY outcome
Timeframe: Day 1 to end of treatment; up to week 24 or week 48Population: The analysis was performed in all evaluable treated participants.
All treated participants were monitored for percent change in Platelet Count from Baseline to the end of the treatment period. The mean percent change in each arm is presented for all evaluable participants.
Outcome measures
| Measure |
Cohort A: HCV GT-2 or GT-3
n=104 Participants
Participants with HCV (Genotype 2 or 3) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for 12 weeks, for a total treatment duration of 24 weeks. Participants received 180μg of Lambda via subcutaneous injection, once weekly, 800 mg/day Ribavirin tablets, orally, twice daily, for a planned duration of 24 weeks. Participants were administered 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants were followed up for a duration of 24 weeks after 24 weeks of treatment.
|
Cohort B: HCV GT-1 or GT-4
n=196 Participants
Participants with HCV (Genotype 1 or 4) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for either 12 or 36 weeks. Participants were administered 180μg of Lambda via subcutaneous injection, once weekly, for a maximum of 48 weeks; body weight stratified dose of Ribavirin tablets, orally, twice daily, for maximum duration of 48 weeks (\<75 kg, total dose was 1000 mg/day, weighing \>=75 kg, total dose was 1200 mg/day); and 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants who achieved an extended rapid virologic response (eRVR) during initial 12 weeks were treated with Lambda/RBV for 12 weeks for total of 24 weeks. Participants who did not achieve eRVR during initial 12 weeks were treated with Lambda/RBV for 36 weeks for total of 48 weeks. Participants were followed up for a duration of 24 weeks after 24 or 48 weeks of treatment.
|
|---|---|---|
|
Mean Percent Change in Platelet Count From Baseline to End of Treatment
|
16.9 Percent change
Interval 12.53 to 21.2
|
20.1 Percent change
Interval 16.1 to 24.16
|
Adverse Events
Cohort A: HCV GT-2 or GT-3
Serious events: 6 serious events
Other events: 70 other events
Deaths: 0 deaths
Cohort B: HCV GT-1 or GT-4
Serious events: 12 serious events
Other events: 159 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Cohort A: HCV GT-2 or GT-3
n=104 participants at risk
Participants with HCV (Genotype 2 or 3) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for 12 weeks, for a total treatment duration of 24 weeks. Participants received 180μg of Lambda via subcutaneous injection, once weekly, 800 mg/day Ribavirin tablets, orally, twice daily, for a planned duration of 24 weeks. Participants were administered 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants were followed up for a duration of 24 weeks after 24 weeks of treatment.
|
Cohort B: HCV GT-1 or GT-4
n=196 participants at risk
Participants with HCV (Genotype 1 or 4) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for either 12 or 36 weeks. Participants were administered 180μg of Lambda via subcutaneous injection, once weekly, for a maximum of 48 weeks; body weight stratified dose of Ribavirin tablets, orally, twice daily, for maximum duration of 48 weeks (\<75 kg, total dose was 1000 mg/day, weighing \>=75 kg, total dose was 1200 mg/day); and 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants who achieved an extended rapid virologic response (eRVR) during initial 12 weeks were treated with Lambda/RBV for 12 weeks for total of 24 weeks. Participants who did not achieve eRVR during initial 12 weeks were treated with Lambda/RBV for 36 weeks for total of 48 weeks. Participants were followed up for a duration of 24 weeks after 24 or 48 weeks of treatment.
|
|---|---|---|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.00%
0/104 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.51%
1/196 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/104 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.51%
1/196 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/104 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.51%
1/196 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Injury, poisoning and procedural complications
Facial bones fracture
|
0.96%
1/104 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.00%
0/196 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/104 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.51%
1/196 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Investigations
International normalised ratio increased
|
0.00%
0/104 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.51%
1/196 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/104 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.51%
1/196 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
General disorders
Multi-Organ failure
|
0.00%
0/104 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.51%
1/196 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
General disorders
Sudden death
|
0.00%
0/104 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
1.0%
2/196 • Number of events 2 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Psychiatric disorders
Dysthymic disorde
|
0.96%
1/104 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.00%
0/196 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Psychiatric disorders
Psychotic disorder
|
0.96%
1/104 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.00%
0/196 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Gastrointestinal disorders
Small intestinal haemorrhage
|
0.00%
0/104 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.51%
1/196 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/104 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.51%
1/196 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/104 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.51%
1/196 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.00%
0/104 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.51%
1/196 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Hepatobiliary disorders
Jaundice
|
1.9%
2/104 • Number of events 2 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
1.0%
2/196 • Number of events 2 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Hepatobiliary disorders
Liver injury
|
0.00%
0/104 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.51%
1/196 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/104 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.51%
1/196 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Metabolism and nutrition disorders
Dehydration
|
0.96%
1/104 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.00%
0/196 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/104 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.51%
1/196 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Infections and infestations
Bronchopulmonary aspergillosis
|
0.00%
0/104 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.51%
1/196 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Infections and infestations
Secondary syphilis
|
0.00%
0/104 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.51%
1/196 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Infections and infestations
Device related infection
|
0.00%
0/104 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
0.51%
1/196 • Number of events 1 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
Other adverse events
| Measure |
Cohort A: HCV GT-2 or GT-3
n=104 participants at risk
Participants with HCV (Genotype 2 or 3) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for 12 weeks, for a total treatment duration of 24 weeks. Participants received 180μg of Lambda via subcutaneous injection, once weekly, 800 mg/day Ribavirin tablets, orally, twice daily, for a planned duration of 24 weeks. Participants were administered 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants were followed up for a duration of 24 weeks after 24 weeks of treatment.
|
Cohort B: HCV GT-1 or GT-4
n=196 participants at risk
Participants with HCV (Genotype 1 or 4) and HIV co-infection were treated with Lambda/RBV/DCV for 12 weeks followed by Lambda/RBV for either 12 or 36 weeks. Participants were administered 180μg of Lambda via subcutaneous injection, once weekly, for a maximum of 48 weeks; body weight stratified dose of Ribavirin tablets, orally, twice daily, for maximum duration of 48 weeks (\<75 kg, total dose was 1000 mg/day, weighing \>=75 kg, total dose was 1200 mg/day); and 30 mg Daclatasvir tablets, orally, once daily, for a maximum of 12 weeks. The total daily dose was 30, 60 or 90 mg depending on the HIV concomitant regimen. Participants who achieved an extended rapid virologic response (eRVR) during initial 12 weeks were treated with Lambda/RBV for 12 weeks for total of 24 weeks. Participants who did not achieve eRVR during initial 12 weeks were treated with Lambda/RBV for 36 weeks for total of 48 weeks. Participants were followed up for a duration of 24 weeks after 24 or 48 weeks of treatment.
|
|---|---|---|
|
Investigations
Aspartate aminotransferase increased
|
7.7%
8/104 • Number of events 10 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
2.0%
4/196 • Number of events 16 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Investigations
Weight decreased
|
3.8%
4/104 • Number of events 5 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
5.6%
11/196 • Number of events 11 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.8%
4/104 • Number of events 4 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
5.1%
10/196 • Number of events 10 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Blood and lymphatic system disorders
Anaemia
|
6.7%
7/104 • Number of events 7 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
8.2%
16/196 • Number of events 16 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Nervous system disorders
Headache
|
9.6%
10/104 • Number of events 13 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
15.8%
31/196 • Number of events 39 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
General disorders
Injection site erythema
|
0.00%
0/104 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
6.1%
12/196 • Number of events 12 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
General disorders
Asthenia
|
21.2%
22/104 • Number of events 24 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
16.3%
32/196 • Number of events 34 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
General disorders
Influenza like illness
|
7.7%
8/104 • Number of events 9 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
2.6%
5/196 • Number of events 6 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
General disorders
Fatigue
|
8.7%
9/104 • Number of events 9 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
24.0%
47/196 • Number of events 53 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
General disorders
Pyrexia
|
2.9%
3/104 • Number of events 4 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
6.6%
13/196 • Number of events 13 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Psychiatric disorders
Depressed mood
|
1.9%
2/104 • Number of events 2 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
7.1%
14/196 • Number of events 15 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Psychiatric disorders
Anxiety
|
3.8%
4/104 • Number of events 4 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
7.7%
15/196 • Number of events 15 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Psychiatric disorders
Depression
|
5.8%
6/104 • Number of events 7 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
9.2%
18/196 • Number of events 18 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Psychiatric disorders
Insomnia
|
15.4%
16/104 • Number of events 19 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
15.8%
31/196 • Number of events 31 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Psychiatric disorders
Irritability
|
14.4%
15/104 • Number of events 16 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
11.7%
23/196 • Number of events 24 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Gastrointestinal disorders
Diarrhoea
|
6.7%
7/104 • Number of events 7 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
15.3%
30/196 • Number of events 43 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Gastrointestinal disorders
Abdominal pain
|
3.8%
4/104 • Number of events 4 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
7.7%
15/196 • Number of events 15 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Gastrointestinal disorders
Dyspepsia
|
3.8%
4/104 • Number of events 4 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
6.1%
12/196 • Number of events 12 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Gastrointestinal disorders
Nausea
|
9.6%
10/104 • Number of events 11 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
18.4%
36/196 • Number of events 51 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Gastrointestinal disorders
Vomiting
|
3.8%
4/104 • Number of events 4 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
11.7%
23/196 • Number of events 32 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Hepatobiliary disorders
Jaundice
|
5.8%
6/104 • Number of events 6 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
5.1%
10/196 • Number of events 11 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
3.8%
4/104 • Number of events 4 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
6.1%
12/196 • Number of events 12 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
14.4%
15/104 • Number of events 17 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
16.8%
33/196 • Number of events 35 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
8.7%
9/104 • Number of events 10 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
13.8%
27/196 • Number of events 27 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.7%
8/104 • Number of events 9 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
13.3%
26/196 • Number of events 28 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
|
Metabolism and nutrition disorders
Decreased appetite
|
8.7%
9/104 • Number of events 10 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
12.2%
24/196 • Number of events 27 • Day 1 to end of treatment; up to week 24 or week 48, SAE: within 30 days of discontinuation of dosing
|
Additional Information
Bristol-Myers Squibb Study Director
Bristol-Myers Squibb
Phone: Please email
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER