Trial Outcomes & Findings for Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab (NCT NCT04320602)
NCT ID: NCT04320602
Last Updated: 2024-09-05
Results Overview
Free C5-associated BTH was defined as BTH concurrent with free C5 concentrations ≥0.5 micrograms (μg)/milliliter (mL). BTH was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath \[dyspnea\], anemia \[hemoglobin \<10 grams {g}/deciliter {dL}\], major adverse vascular event \[MAVE\], including thrombosis, dysphagia, or erectile dysfunction) in the presence of elevated lactate dehydrogenase (LDH) ≥2 \* upper limit of normal (ULN).
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
18 participants
Primary outcome timeframe
Baseline through Day 351
Results posted on
2024-09-05
Participant Flow
The study consisted of a Screening Period of approximately 3 months and a Treatment Period of 351 days. Eligible participants were administered eculizumab 1200 milligrams (mg) every 2 weeks (q2w) optionally at home at the discretion of the Investigator, and preference of the participant during the Screening Period.
Participant milestones
| Measure |
Ravulizumab
Participants received a loading dose of ravulizumab on Day 1 and maintenance treatment with ravulizumab on Day 15 and every 8 weeks (q8w) thereafter until Day 351. Ravulizumab loading and maintenance doses were based on the participant's body weight measured at the prior visit, per approved dosing regimen.
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|---|---|
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Overall Study
STARTED
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18
|
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Overall Study
Received at Least 1 Dose of Study Drug
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18
|
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Overall Study
COMPLETED
|
18
|
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Overall Study
NOT COMPLETED
|
0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab
Baseline characteristics by cohort
| Measure |
Ravulizumab
n=18 Participants
Participants received a loading dose of ravulizumab on Day 1 and maintenance treatment with ravulizumab on Day 15 and q8w thereafter until Day 351. Ravulizumab loading and maintenance doses were based on the participant's body weight measured at the prior visit, per approved dosing regimen.
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|---|---|
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Age, Continuous
|
55.7 years
STANDARD_DEVIATION 11.34 • n=5 Participants
|
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Age, Customized
In utero
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0 Participants
n=5 Participants
|
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Age, Customized
Preterm newborn infants (gestational age < 37 wks)
|
0 Participants
n=5 Participants
|
|
Age, Customized
Newborns (0-27 days)
|
0 Participants
n=5 Participants
|
|
Age, Customized
Infants and toddlers (28 days-23 months)
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0 Participants
n=5 Participants
|
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Age, Customized
Children (2-11 years)
|
0 Participants
n=5 Participants
|
|
Age, Customized
Adolescents (12-17 years)
|
0 Participants
n=5 Participants
|
|
Age, Customized
Adults (18-64 years)
|
15 Participants
n=5 Participants
|
|
Age, Customized
From 65-84 years
|
3 Participants
n=5 Participants
|
|
Age, Customized
85 years and over
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0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
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Ethnicity (NIH/OMB)
Hispanic or Latino
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0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
18 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline through Day 351Population: The FAS included all participants who received at least 1 dose of ravulizumab.
Free C5-associated BTH was defined as BTH concurrent with free C5 concentrations ≥0.5 micrograms (μg)/milliliter (mL). BTH was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath \[dyspnea\], anemia \[hemoglobin \<10 grams {g}/deciliter {dL}\], major adverse vascular event \[MAVE\], including thrombosis, dysphagia, or erectile dysfunction) in the presence of elevated lactate dehydrogenase (LDH) ≥2 \* upper limit of normal (ULN).
Outcome measures
| Measure |
Ravulizumab
n=18 Participants
Participants received a loading dose of ravulizumab on Day 1 and maintenance treatment with ravulizumab on Day 15 and q8w thereafter until Day 351. Ravulizumab loading and maintenance doses were based on the participant's body weight measured at the prior visit, per approved dosing regimen.
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|---|---|
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Percentage of Participants Who Experienced Free C5-associated BTH
|
0 percentage of participants
95% Confidence Interval 0 • Interval 0.0 to 18.5
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SECONDARY outcome
Timeframe: Baseline through Day 351Population: The FAS included all participants who received at least 1 dose of ravulizumab.
BTH was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath \[dyspnea\], anemia \[hemoglobin \<10 g/dL\], MAVE, including thrombosis, dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2 \* ULN.
Outcome measures
| Measure |
Ravulizumab
n=18 Participants
Participants received a loading dose of ravulizumab on Day 1 and maintenance treatment with ravulizumab on Day 15 and q8w thereafter until Day 351. Ravulizumab loading and maintenance doses were based on the participant's body weight measured at the prior visit, per approved dosing regimen.
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|---|---|
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Percentage of Participants Who Experienced BTH
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5.6 percentage of participants
95% Confidence Interval 0.1 • Interval 0.1 to 27.3
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SECONDARY outcome
Timeframe: Baseline, Day 351Population: The FAS included all participants who received at least 1 dose of ravulizumab. Here, 'Overall number of participants analyzed' = participants evaluable for this endpoint.
Outcome measures
| Measure |
Ravulizumab
n=14 Participants
Participants received a loading dose of ravulizumab on Day 1 and maintenance treatment with ravulizumab on Day 15 and q8w thereafter until Day 351. Ravulizumab loading and maintenance doses were based on the participant's body weight measured at the prior visit, per approved dosing regimen.
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|---|---|
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Percent Change From Baseline in LDH at Day 351
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-0.81 percent change
Standard Error 6.132 • Interval 6.132 to
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SECONDARY outcome
Timeframe: Baseline through Day 351Population: The FAS included all participants who received at least 1 dose of ravulizumab.
Outcome measures
| Measure |
Ravulizumab
n=18 Participants
Participants received a loading dose of ravulizumab on Day 1 and maintenance treatment with ravulizumab on Day 15 and q8w thereafter until Day 351. Ravulizumab loading and maintenance doses were based on the participant's body weight measured at the prior visit, per approved dosing regimen.
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|---|---|
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Percentage of Participants Who Received a Red Blood Cell (RBC) Transfusion
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33.3 percentage of participants
95% Confidence Interval 13.3 • Interval 13.3 to 59.0
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SECONDARY outcome
Timeframe: Baseline through Day 351Population: The FAS included all participants who received at least 1 dose of ravulizumab.
Stabilized hemoglobin was defined as avoidance of a ≥2 g/dL decrease in hemoglobin level from baseline in the absence of transfusion from Baseline to Day 351.
Outcome measures
| Measure |
Ravulizumab
n=18 Participants
Participants received a loading dose of ravulizumab on Day 1 and maintenance treatment with ravulizumab on Day 15 and q8w thereafter until Day 351. Ravulizumab loading and maintenance doses were based on the participant's body weight measured at the prior visit, per approved dosing regimen.
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|---|---|
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Percentage of Participants With Stabilized Hemoglobin
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61.1 percentage of participants
95% Confidence Interval 35.7 • Interval 35.7 to 82.7
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Adverse Events
Ravulizumab
Serious events: 3 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ravulizumab
n=18 participants at risk
Participants received a loading dose of ravulizumab on Day 1 and maintenance treatment with ravulizumab on Day 15 and q8w thereafter until Day 351. Ravulizumab loading and maintenance doses were based on the participant's body weight measured at the prior visit, per approved dosing regimen.
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|---|---|
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Infections and infestations
Pneumonia
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5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
|
Infections and infestations
Urinary tract infection
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
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Eye disorders
Retinal haemorrhage
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
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General disorders
Pyrexia
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
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Nervous system disorders
Headache
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
Other adverse events
| Measure |
Ravulizumab
n=18 participants at risk
Participants received a loading dose of ravulizumab on Day 1 and maintenance treatment with ravulizumab on Day 15 and q8w thereafter until Day 351. Ravulizumab loading and maintenance doses were based on the participant's body weight measured at the prior visit, per approved dosing regimen.
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|---|---|
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General disorders
Fatigue
|
33.3%
6/18 • Number of events 8 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
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General disorders
Non-cardiac chest pain
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11.1%
2/18 • Number of events 2 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
|
General disorders
Asthenia
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5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
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General disorders
Chest discomfort
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
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General disorders
Influenza like illness
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
|
General disorders
Pain
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
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General disorders
Peripheral swelling
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5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
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Respiratory, thoracic and mediastinal disorders
Cough
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16.7%
3/18 • Number of events 3 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
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Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
11.1%
2/18 • Number of events 2 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
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Respiratory, thoracic and mediastinal disorders
Upper respiratory tract congestion
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5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
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Infections and infestations
COVID-19
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16.7%
3/18 • Number of events 3 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
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Infections and infestations
Nasopharyngitis
|
11.1%
2/18 • Number of events 3 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
|
Infections and infestations
Herpes zoster
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
|
Infections and infestations
Upper respiratory tract infection
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
|
Infections and infestations
Urinary tract infection
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
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Investigations
SARS-CoV-2 test positive
|
16.7%
3/18 • Number of events 3 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
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|
Investigations
Body temperature abnormal
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
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Investigations
Haemoglobin decreased
|
5.6%
1/18 • Number of events 2 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
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Skin and subcutaneous tissue disorders
Nail ridging
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
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Skin and subcutaneous tissue disorders
Neurodermatitis
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
3/18 • Number of events 3 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
|
Gastrointestinal disorders
Constipation
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.1%
2/18 • Number of events 2 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
|
Renal and urinary disorders
Chromaturia
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
|
Renal and urinary disorders
Haemoglobinuria
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
|
Renal and urinary disorders
Nephrolithiasis
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
|
Blood and lymphatic system disorders
Extravascular haemolysis
|
5.6%
1/18 • Number of events 1 • Baseline through Day 351
Safety set included all participants who received at least 1 dose of ravulizumab.
|
Additional Information
Alexion Pharmaceuticals Inc.
Alexion Pharmaceuticals Inc.
Phone: 855-752-2356
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place