Trial Outcomes & Findings for Open-label, Multiple Ascending Dose Study of Ravulizumab (ALXN1210) in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) (NCT NCT02605993)
NCT ID: NCT02605993
Last Updated: 2023-01-04
Results Overview
The percent change in LDH levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
26 participants
Primary outcome timeframe
Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
Results posted on
2023-01-04
Participant Flow
Participant milestones
| Measure |
Cohort 1
During the Treatment Period, participants were administered ravulizumab 1400 milligrams (mg) on Day 1, ravulizumab 1000 mg on Day 15 and Day 29, and then ravulizumab 1000 mg every 4 weeks for 7 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kilograms (kg), 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 2
During the Treatment Period, participants were administered ravulizumab 2000 mg on Day 1, ravulizumab 1600 mg on Day 22 and Day 43, and then ravulizumab 1600 mg every 6 weeks for 4 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 3
During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 4
During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years.
|
|---|---|---|---|---|
|
Treatment Period
STARTED
|
6
|
6
|
7
|
7
|
|
Treatment Period
Received at Least 1 Dose of Study Drug
|
6
|
6
|
7
|
7
|
|
Treatment Period
COMPLETED
|
6
|
6
|
7
|
7
|
|
Treatment Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Extension Period
STARTED
|
6
|
6
|
7
|
7
|
|
Extension Period
Received at Least 1 Dose of Study Drug
|
6
|
6
|
7
|
7
|
|
Extension Period
COMPLETED
|
6
|
6
|
6
|
7
|
|
Extension Period
NOT COMPLETED
|
0
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Cohort 1
During the Treatment Period, participants were administered ravulizumab 1400 milligrams (mg) on Day 1, ravulizumab 1000 mg on Day 15 and Day 29, and then ravulizumab 1000 mg every 4 weeks for 7 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kilograms (kg), 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 2
During the Treatment Period, participants were administered ravulizumab 2000 mg on Day 1, ravulizumab 1600 mg on Day 22 and Day 43, and then ravulizumab 1600 mg every 6 weeks for 4 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 3
During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 4
During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years.
|
|---|---|---|---|---|
|
Extension Period
Participant underwent bone marrow transplantation due to chronic myelomonocytic leukemia
|
0
|
0
|
1
|
0
|
Baseline Characteristics
Open-label, Multiple Ascending Dose Study of Ravulizumab (ALXN1210) in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Baseline characteristics by cohort
| Measure |
Cohort 1
n=6 Participants
During the Treatment Period, participants were administered ravulizumab 1400 mg on Day 1, ravulizumab 1000 mg on Day 15 and Day 29, and then ravulizumab 1000 mg every 4 weeks for 7 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 2
n=6 Participants
During the Treatment Period, participants were administered ravulizumab 2000 mg on Day 1, ravulizumab 1600 mg on Day 22 and Day 43, and then ravulizumab 1600 mg every 6 weeks for 4 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 3
n=7 Participants
During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 4
n=7 Participants
During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years.
|
Total
n=26 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
43.1 years
STANDARD_DEVIATION 14.57 • n=5 Participants
|
48.6 years
STANDARD_DEVIATION 23.48 • n=7 Participants
|
37.3 years
STANDARD_DEVIATION 14.03 • n=5 Participants
|
48.5 years
STANDARD_DEVIATION 13.43 • n=4 Participants
|
44.3 years
STANDARD_DEVIATION 16.33 • n=21 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
20 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
22 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
White
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
15 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Not Reported
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Lactate Dehydrogenase (LDH) Levels
|
1026.88 units/liter (U/L)
STANDARD_DEVIATION 547.843 • n=5 Participants
|
1223.55 units/liter (U/L)
STANDARD_DEVIATION 149.693 • n=7 Participants
|
2127.57 units/liter (U/L)
STANDARD_DEVIATION 815.875 • n=5 Participants
|
2142.24 units/liter (U/L)
STANDARD_DEVIATION 366.511 • n=4 Participants
|
1668.90 units/liter (U/L)
STANDARD_DEVIATION 724.341 • n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)Population: Full Analysis Set: Participants in the safety set with a Baseline and at least 1 LDH measurement after first dose of ravulizumab. Data summarized only for participants with data at Baseline and the specified time point. Last observation carried forward (LOCF) was used for participants with a missing Day 253 or Day 281 assessment.
The percent change in LDH levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.
Outcome measures
| Measure |
Cohort 1
n=6 Participants
During the Treatment Period, participants were administered ravulizumab 1400 mg on Day 1, ravulizumab 1000 mg on Day 15 and Day 29, and then ravulizumab 1000 mg every 4 weeks for 7 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 2
n=6 Participants
During the Treatment Period, participants were administered ravulizumab 2000 mg on Day 1, ravulizumab 1600 mg on Day 22 and Day 43, and then ravulizumab 1600 mg every 6 weeks for 4 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 3
n=7 Participants
During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 4
n=7 Participants
During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years.
|
|---|---|---|---|---|
|
Percent Change In LDH Levels From Baseline To Day 253 And Day 281
Day 253
|
-72.85 Percent Change
Standard Deviation 12.082
|
-78.12 Percent Change
Standard Deviation 6.635
|
-84.96 Percent Change
Standard Deviation 4.423
|
-87.63 Percent Change
Standard Deviation 6.923
|
|
Percent Change In LDH Levels From Baseline To Day 253 And Day 281
Day 281
|
—
|
—
|
—
|
-89.89 Percent Change
Standard Deviation 2.885
|
SECONDARY outcome
Timeframe: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)Population: Full Analysis Set: Participants in the safety set with a Baseline and at least 1 LDH measurement after first dose of ravulizumab. Data summarized only for participants with data at Baseline and the specified time point. LOCF was used for participants with a missing Day 253 or Day 281 assessment.
The percent change in free hemoglobin levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.
Outcome measures
| Measure |
Cohort 1
n=6 Participants
During the Treatment Period, participants were administered ravulizumab 1400 mg on Day 1, ravulizumab 1000 mg on Day 15 and Day 29, and then ravulizumab 1000 mg every 4 weeks for 7 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 2
n=6 Participants
During the Treatment Period, participants were administered ravulizumab 2000 mg on Day 1, ravulizumab 1600 mg on Day 22 and Day 43, and then ravulizumab 1600 mg every 6 weeks for 4 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 3
n=7 Participants
During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 4
n=7 Participants
During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years.
|
|---|---|---|---|---|
|
Percent Change In Free Hemoglobin Levels From Baseline To Day 253 And Day 281
Day 253
|
14.07 Percent Change
Standard Deviation 124.755
|
-12.32 Percent Change
Standard Deviation 57.213
|
-22.14 Percent Change
Standard Deviation 94.388
|
-40.80 Percent Change
Standard Deviation 27.474
|
|
Percent Change In Free Hemoglobin Levels From Baseline To Day 253 And Day 281
Day 281
|
—
|
—
|
—
|
-45.64 Percent Change
Standard Deviation 28.938
|
SECONDARY outcome
Timeframe: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)Population: Full Analysis Set: Participants in the safety set with a Baseline and at least 1 LDH measurement after first dose of ravulizumab. Data summarized only for participants with data at Baseline and the specified time point. LOCF was used for participants with a missing Day 253 or Day 281 assessment.
The percent change in haptoglobin levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.
Outcome measures
| Measure |
Cohort 1
n=6 Participants
During the Treatment Period, participants were administered ravulizumab 1400 mg on Day 1, ravulizumab 1000 mg on Day 15 and Day 29, and then ravulizumab 1000 mg every 4 weeks for 7 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 2
n=6 Participants
During the Treatment Period, participants were administered ravulizumab 2000 mg on Day 1, ravulizumab 1600 mg on Day 22 and Day 43, and then ravulizumab 1600 mg every 6 weeks for 4 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 3
n=7 Participants
During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 4
n=7 Participants
During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years.
|
|---|---|---|---|---|
|
Percent Change In Haptoglobin Levels From Baseline To Day 253 And Day 281
Day 253
|
21.67 Percent Change
Standard Deviation 53.072
|
81.67 Percent Change
Standard Deviation 200.042
|
4.29 Percent Change
Standard Deviation 11.339
|
34.29 Percent Change
Standard Deviation 74.578
|
|
Percent Change In Haptoglobin Levels From Baseline To Day 253 And Day 281
Day 281
|
—
|
—
|
—
|
27.14 Percent Change
Standard Deviation 56.188
|
SECONDARY outcome
Timeframe: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)Population: Full Analysis Set: Participants in the safety set with a Baseline and at least 1 LDH measurement after first dose of ravulizumab. Data summarized only for participants with data at Baseline and the specified time point. LOCF was used for participants with a missing Day 253 or Day 281 assessment.
The percent change in reticulocyte/erythrocyte count levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.
Outcome measures
| Measure |
Cohort 1
n=6 Participants
During the Treatment Period, participants were administered ravulizumab 1400 mg on Day 1, ravulizumab 1000 mg on Day 15 and Day 29, and then ravulizumab 1000 mg every 4 weeks for 7 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 2
n=6 Participants
During the Treatment Period, participants were administered ravulizumab 2000 mg on Day 1, ravulizumab 1600 mg on Day 22 and Day 43, and then ravulizumab 1600 mg every 6 weeks for 4 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 3
n=7 Participants
During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 4
n=7 Participants
During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years.
|
|---|---|---|---|---|
|
Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 253 And Day 281
Day 253
|
-1.27 Percent Change
Standard Deviation 43.019
|
-5.05 Percent Change
Standard Deviation 35.691
|
10.46 Percent Change
Standard Deviation 59.510
|
14.66 Percent Change
Standard Deviation 81.390
|
|
Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 253 And Day 281
Day 281
|
—
|
—
|
—
|
-4.66 Percent Change
Standard Deviation 68.502
|
SECONDARY outcome
Timeframe: Baseline, Day 253 (Cohorts 1 to 4)Population: Full Analysis Set: Participants in the safety set with a Baseline and at least 1 LDH measurement after first dose of ravulizumab. Data summarized only for participants with data at Baseline and the specified time point. LOCF was used for participants with a missing Day 253 assessment.
The percent change in paroxysmal nocturnal hemoglobinuria (PNH) red blood cell (RBC), summed types II and III, clone size levels were assessed from Baseline to Day 253 for Cohorts 1 to 4.
Outcome measures
| Measure |
Cohort 1
n=6 Participants
During the Treatment Period, participants were administered ravulizumab 1400 mg on Day 1, ravulizumab 1000 mg on Day 15 and Day 29, and then ravulizumab 1000 mg every 4 weeks for 7 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 2
n=6 Participants
During the Treatment Period, participants were administered ravulizumab 2000 mg on Day 1, ravulizumab 1600 mg on Day 22 and Day 43, and then ravulizumab 1600 mg every 6 weeks for 4 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 3
n=7 Participants
During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 4
n=7 Participants
During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years.
|
|---|---|---|---|---|
|
Percent Change In PNH RBC Types II And III Clone Size From Baseline To Day 253
|
6.65 Percent Change
Standard Deviation 24.101
|
5.47 Percent Change
Standard Deviation 21.940
|
54.14 Percent Change
Standard Deviation 98.713
|
88.21 Percent Change
Standard Deviation 138.290
|
SECONDARY outcome
Timeframe: Baseline to Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)Population: Full Analysis Set: Participants in the safety set with a Baseline and at least 1 LDH measurement after first dose of ravulizumab. Data summarized only for participants with data at Baseline and the specified time point. LOCF is used for participants with a missing Day 253 or Day 281 assessment.
The percent change in D-dimer levels were assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.
Outcome measures
| Measure |
Cohort 1
n=6 Participants
During the Treatment Period, participants were administered ravulizumab 1400 mg on Day 1, ravulizumab 1000 mg on Day 15 and Day 29, and then ravulizumab 1000 mg every 4 weeks for 7 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 2
n=6 Participants
During the Treatment Period, participants were administered ravulizumab 2000 mg on Day 1, ravulizumab 1600 mg on Day 22 and Day 43, and then ravulizumab 1600 mg every 6 weeks for 4 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 3
n=7 Participants
During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 4
n=6 Participants
During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years.
|
|---|---|---|---|---|
|
Percent Change In D-dimer From Baseline To Day 253 And Day 281
Day 253
|
-24.80 Percent Change
Standard Deviation 32.436
|
-29.47 Percent Change
Standard Deviation 26.547
|
-10.90 Percent Change
Standard Deviation 41.032
|
-16.08 Percent Change
Standard Deviation 34.783
|
|
Percent Change In D-dimer From Baseline To Day 253 And Day 281
Day 281
|
—
|
—
|
—
|
-27.05 Percent Change
Standard Deviation 27.663
|
SECONDARY outcome
Timeframe: Baseline, Day 253 (Cohorts 1 to 3) and Day 281 (Cohort 4)Population: Full Analysis Set: Participants in the safety set with a Baseline and at least 1 LDH measurement after first dose of ravulizumab. Data summarized only for participants with data at Baseline and the specified time point. LOCF is used for participants with a missing Day 253 or Day 281 assessment. Erectile dysfunction affects only male participants.
Clinical manifestations were assessed from Baseline to Day 253 for Cohorts 1 to 3 and from Baseline to Day 281 for Cohort 4 only. Clinical manifestations were defined as fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction (male participants only). Improvement was defined as present at Baseline and absent at Day endpoint. Worsening was defined as absent at Baseline and present at Day endpoint. No Change was defined as no change from Baseline and time point of endpoint.
Outcome measures
| Measure |
Cohort 1
n=6 Participants
During the Treatment Period, participants were administered ravulizumab 1400 mg on Day 1, ravulizumab 1000 mg on Day 15 and Day 29, and then ravulizumab 1000 mg every 4 weeks for 7 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 2
n=6 Participants
During the Treatment Period, participants were administered ravulizumab 2000 mg on Day 1, ravulizumab 1600 mg on Day 22 and Day 43, and then ravulizumab 1600 mg every 6 weeks for 4 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 3
n=7 Participants
During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 4
n=7 Participants
During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years.
|
|---|---|---|---|---|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Dysphagia at Day 253 · Worsened from Baseline
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Dysphagia at Day 281 · Worsened from Baseline
|
—
|
—
|
—
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Chest Pain at Day 253 · Worsened from Baseline
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Erectile Dysfunction at Day 253 · Improved from Baseline
|
2 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Fatigue at Day 253 · Improved from Baseline
|
4 Participants
|
2 Participants
|
3 Participants
|
3 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Fatigue at Day 253 · Worsened from Baseline
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Fatigue at Day 253 · No Change
|
2 Participants
|
4 Participants
|
4 Participants
|
4 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Fatigue at Day 253 · Not Applicable
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Fatigue at Day 281 · Improved from Baseline
|
—
|
—
|
—
|
4 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Fatigue at Day 281 · Worsened from Baseline
|
—
|
—
|
—
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Fatigue at Day 281 · No Change
|
—
|
—
|
—
|
3 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Fatigue at Day 281 · Not Applicable
|
—
|
—
|
—
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Abdominal Pain at Day 253 · Improved from Baseline
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Abdominal Pain at Day 253 · Worsened from Baseline
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Abdominal Pain at Day 253 · No Change
|
5 Participants
|
5 Participants
|
6 Participants
|
7 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Abdominal Pain at Day 253 · Not Applicable
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Abdominal Pain at Day 281 · Improved from Baseline
|
—
|
—
|
—
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Abdominal Pain at Day 281 · Worsened from Baseline
|
—
|
—
|
—
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Abdominal Pain at Day 281 · No Change
|
—
|
—
|
—
|
7 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Abdominal Pain at Day 281 · Not Applicable
|
—
|
—
|
—
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Dyspnea at Day 253 · Improved from Baseline
|
1 Participants
|
1 Participants
|
4 Participants
|
2 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Dyspnea at Day 253 · Worsened from Baseline
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Dyspnea at Day 253 · No Change
|
5 Participants
|
5 Participants
|
3 Participants
|
5 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Dyspnea at Day 253 · Not Applicable
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Dyspnea at Day 281 · Improved from Baseline
|
—
|
—
|
—
|
2 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Dyspnea at Day 281 · Worsened from Baseline
|
—
|
—
|
—
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Dyspnea at Day 281 · No Change
|
—
|
—
|
—
|
5 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Dyspnea at Day 281 · Not Applicable
|
—
|
—
|
—
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Dysphagia at Day 253 · Improved from Baseline
|
0 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Dysphagia at Day 253 · No Change
|
6 Participants
|
5 Participants
|
6 Participants
|
6 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Dysphagia at Day 253 · Not Applicable
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Dysphagia at Day 281 · Improved from Baseline
|
—
|
—
|
—
|
1 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Dysphagia at Day 281 · No Change
|
—
|
—
|
—
|
6 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Dysphagia at Day 281 · Not Applicable
|
—
|
—
|
—
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Chest Pain at Day 253 · Improved from Baseline
|
1 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Chest Pain at Day 253 · No Change
|
5 Participants
|
6 Participants
|
5 Participants
|
7 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Chest Pain at Day 253 · Not Applicable
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Chest Pain at Day 281 · Improved from Baseline
|
—
|
—
|
—
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Chest Pain at Day 281 · Worsened from Baseline
|
—
|
—
|
—
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Chest Pain at Day 281 · No Change
|
—
|
—
|
—
|
7 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Chest Pain at Day 281 · Not Applicable
|
—
|
—
|
—
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Erectile Dysfunction at Day 253 · Worsened from Baseline
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Erectile Dysfunction at Day 253 · No Change
|
2 Participants
|
5 Participants
|
5 Participants
|
4 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Erectile Dysfunction at Day 253 · Not Applicable
|
2 Participants
|
1 Participants
|
1 Participants
|
2 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Erectile Dysfunction at Day 281 · Improved from Baseline
|
—
|
—
|
—
|
1 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Erectile Dysfunction at Day 281 · Worsened from Baseline
|
—
|
—
|
—
|
0 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Erectile Dysfunction at Day 281 · No Change
|
—
|
—
|
—
|
4 Participants
|
|
Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281
Erectile Dysfunction at Day 281 · Not Applicable
|
—
|
—
|
—
|
2 Participants
|
Adverse Events
Cohort 1
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
Cohort 2
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
Cohort 3
Serious events: 4 serious events
Other events: 7 other events
Deaths: 0 deaths
Cohort 4
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cohort 1
n=6 participants at risk
During the Treatment Period, participants were administered ravulizumab 1400 mg on Day 1, ravulizumab 1000 mg on Day 15 and Day 29, and then ravulizumab 1000 mg every 4 weeks for 7 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 2
n=6 participants at risk
During the Treatment Period, participants were administered ravulizumab 2000 mg on Day 1, ravulizumab 1600 mg on Day 22 and Day 43, and then ravulizumab 1600 mg every 6 weeks for 4 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 3
n=7 participants at risk
During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 4
n=7 participants at risk
During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Blood and lymphatic system disorders
Haemolysis
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
General disorders
Pyrexia
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Meningococcal infection
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Meningococcal sepsis
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Nervous system disorders
Headache
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Infection
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Klebsiella bacteraemia
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Enterobacter bacteraemia
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Enterobacter sepsis
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Epididymitis
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Escherichia urinary tract infection
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Febrile infection
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Gonococcal infection
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Klebsiella sepsis
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Sepsis
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Urinary tract infection bacterial
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Blood and lymphatic system disorders
Breakthrough haemolysis
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Gastrointestinal disorders
Food poisoning
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Gastrointestinal disorders
Large intestinal haemorrhage
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
General disorders
Generalised oedema
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Hepatobiliary disorders
Biliary obstruction
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Nervous system disorders
Seizure
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Renal and urinary disorders
Renal colic
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Cardiac disorders
Myocardial ischaemia
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Injury, poisoning and procedural complications
Post procedural complication
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
Other adverse events
| Measure |
Cohort 1
n=6 participants at risk
During the Treatment Period, participants were administered ravulizumab 1400 mg on Day 1, ravulizumab 1000 mg on Day 15 and Day 29, and then ravulizumab 1000 mg every 4 weeks for 7 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 2
n=6 participants at risk
During the Treatment Period, participants were administered ravulizumab 2000 mg on Day 1, ravulizumab 1600 mg on Day 22 and Day 43, and then ravulizumab 1600 mg every 6 weeks for 4 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 3
n=7 participants at risk
During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses. In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.
|
Cohort 4
n=7 participants at risk
During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses. During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
28.6%
2/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Cardiac disorders
Cardiovascular disorder
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Cardiac disorders
Tachycardia
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Gastrointestinal disorders
Abdominal pain upper
|
33.3%
2/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Gastrointestinal disorders
Dyspepsia
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Gastrointestinal disorders
Gastritis
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Gastrointestinal disorders
Inguinal hernia
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
28.6%
2/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
General disorders
Asthenia
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
General disorders
Chest pain
|
33.3%
2/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
General disorders
Fatigue
|
50.0%
3/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
33.3%
2/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
General disorders
Oedema peripheral
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
General disorders
Pyrexia
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
28.6%
2/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
General disorders
Pain
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
General disorders
Influenza like illness
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
33.3%
2/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Upper respiratory tract infection
|
33.3%
2/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
71.4%
5/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
57.1%
4/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Nasopharyngitis
|
66.7%
4/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
33.3%
2/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
42.9%
3/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
28.6%
2/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Respiratory tract infection
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Urinary tract infection
|
33.3%
2/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Influenza
|
33.3%
2/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
33.3%
2/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Gastroenteritis
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
28.6%
2/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Cystitis
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Gastrointestinal infection
|
33.3%
2/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Infections and infestations
Rhinitis
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Injury, poisoning and procedural complications
Post-traumatic pain
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
28.6%
2/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
28.6%
2/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Investigations
Blood creatinine increased
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Investigations
Neutrophil count decreased
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
50.0%
3/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
28.6%
2/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
66.7%
4/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
28.6%
2/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
33.3%
2/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
28.6%
2/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Nervous system disorders
Dizziness
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
42.9%
3/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Nervous system disorders
Headache
|
50.0%
3/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
83.3%
5/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
57.1%
4/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
42.9%
3/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Renal and urinary disorders
Chromaturia
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Renal and urinary disorders
Haemoglobinuria
|
33.3%
2/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
28.6%
2/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
50.0%
3/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
33.3%
2/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
28.6%
2/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
33.3%
2/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Vascular disorders
Hypertension
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Blood and lymphatic system disorders
Haemolysis
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
28.6%
2/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Gastrointestinal disorders
Abdominal pain
|
50.0%
3/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
28.6%
2/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
42.9%
3/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Gastrointestinal disorders
Nausea
|
33.3%
2/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
28.6%
2/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
33.3%
2/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Hepatobiliary disorders
Ocular icterus
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
33.3%
2/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
16.7%
1/6 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
0.00%
0/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
14.3%
1/7 • Adverse events were monitored continuously from Screening to Day 253 (for Cohorts 1, 2, and 3) and Day 281 (for Cohort 4) (Treatment Period) and up to Day 2157 (Extension Period).
|
Additional Information
Alexion Pharmaceuticals, Inc.
Alexion Pharmaceuticals, Inc.
Phone: +1-855-752-2356
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place