Trial Outcomes & Findings for Study of Ravulizumab in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS) (NCT NCT03131219)

Last Updated: 2024-03-15

Results Overview

Complete TMA response during the 26-week Initial Evaluation Period is a composite outcome measure that required normalization of hematological parameters (platelet count and lactate dehydrogenase \[LDH\]) and improvement in kidney function (≥25% reduction in serum creatinine from baseline); for participants on dialysis, baseline was established at least 6 days after the end of dialysis. Participants had to meet these criteria for 2 separate assessments obtained at least 4 weeks (28 days) apart, and any measurement in between. To be considered a responder during the 26-week Initial Evaluation Period, the latest time point a participant could first meet the response criteria was 28 days before the Week 26 (Day 183) assessment. Formal statistical comparison analyses were not planned for this study. Percentage based on the responders among treated participants. Confidence interval (CI) based on exact confidence limits using the Clopper Pearson method.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

34 participants

Primary outcome timeframe

Week 26

Results posted on

2024-03-15

Participant Flow

Participant milestones

Participant milestones
Measure	Complement Inhibitor Treatment Naïve Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.	Eculizumab Experienced Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.
Initial Evaluation Period STARTED	24	10
Initial Evaluation Period Received At Least 1 Dose of Study Drug	24	10
Initial Evaluation Period COMPLETED	17	10
Initial Evaluation Period NOT COMPLETED	7	0
Extension Period STARTED	17	10
Extension Period Received At Least 1 Dose of Study Drug	17	10
Extension Period COMPLETED	16	10
Extension Period NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Complement Inhibitor Treatment Naïve Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.	Eculizumab Experienced Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.
Initial Evaluation Period Adverse Event	2	0
Initial Evaluation Period Protocol Violation	1	0
Initial Evaluation Period Deemed Ineligible Post Treatment	3	0
Initial Evaluation Period Physician Decision	1	0
Extension Period Physician Decision	1	0

Baseline Characteristics

Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, and met pre-specified eligibility criteria.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Complement Inhibitor Treatment Naïve n=24 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.	Eculizumab Experienced n=10 Participants Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.	Total n=34 Participants Total of all reporting groups
Age, Continuous	6.0 years STANDARD_DEVIATION 4.79 • n=24 Participants	11.0 years STANDARD_DEVIATION 4.97 • n=10 Participants	8.1 years STANDARD_DEVIATION 5.17 • n=34 Participants
Sex: Female, Male Female	14 Participants n=24 Participants	1 Participants n=10 Participants	15 Participants n=34 Participants
Sex: Female, Male Male	10 Participants n=24 Participants	9 Participants n=10 Participants	19 Participants n=34 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=24 Participants	1 Participants n=10 Participants	3 Participants n=34 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	22 Participants n=24 Participants	9 Participants n=10 Participants	31 Participants n=34 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=24 Participants	0 Participants n=10 Participants	0 Participants n=34 Participants
Baseline Estimated Glomerular Filtration Rate (eGFR)	26.4 mL/min/1.73 m^2 STANDARD_DEVIATION 21.17 • n=18 Participants • Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, and met pre-specified eligibility criteria.	104.90 mL/min/1.73 m^2 STANDARD_DEVIATION 29.545 • n=10 Participants • Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, and met pre-specified eligibility criteria.	NA mL/min/1.73 m^2 STANDARD_DEVIATION NA • n=28 Participants • Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, and met pre-specified eligibility criteria.

PRIMARY outcome

Timeframe: Week 26

Population: Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, and met pre-specified eligibility criteria. Here, Overall 'Number of Participants Analyzed' signifies those who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Complement Inhibitor Treatment Naïve n=17 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.	Eculizumab Experienced Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.
Percentage Of Complement Inhibitor Treatment-naïve Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26 Complete TMA response	77.8 percentage of participants Interval 52.4 to 93.6	—
Percentage Of Complement Inhibitor Treatment-naïve Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26 Platelet count normalization	94.4 percentage of participants Interval 72.7 to 99.9	—
Percentage Of Complement Inhibitor Treatment-naïve Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26 LDH normalization	88.9 percentage of participants Interval 65.3 to 98.6	—
Percentage Of Complement Inhibitor Treatment-naïve Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26 ≥ 25% improvement in serum creatinine from baseline	83.3 percentage of participants Interval 58.6 to 96.4	—

SECONDARY outcome

Timeframe: Baseline through at least Week 52 and up to Week 111

Population: Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, and met pre-specified eligibility criteria.

Participants that did not have a response were censored at the date of last visit or study discontinuation at the time when the analysis was performed. The time to complete TMA Response is reported in days. The time of the event of a confirmed complete TMA response was considered the first time point at which all the criteria for complete TMA response were met. Participants had to meet all complete TMA response criteria at 2 separate assessments obtained at least 4 weeks (28 days) apart, and any measurement in between.

Outcome measures

Outcome measures
Measure	Complement Inhibitor Treatment Naïve n=18 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.	Eculizumab Experienced Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.
Time To Complete TMA Response In Complement Inhibitor Treatment-naïve Participants	30.0 days Interval 22.0 to 88.0	—

SECONDARY outcome

Timeframe: Week 52

Population: Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, met pre-specified eligibility criteria, and had evaluable data at specified timepoint. Here, Overall 'Number of Participants Analyzed' signifies those who were evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable for specified categories.

The proportion of participants considered responders, along with a 2-sided 95% CI based on exact confidence limits using the Clopper Pearson method is reported.

Outcome measures

Outcome measures
Measure	Complement Inhibitor Treatment Naïve n=17 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.	Eculizumab Experienced Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.
Proportion Of Complement Inhibitor Treatment-naïve Participants With Complete TMA Response At Week 52 Platelet count normalization	0.882 proportion of participants Interval 0.636 to 0.985	—
Proportion Of Complement Inhibitor Treatment-naïve Participants With Complete TMA Response At Week 52 Complete TMA responder	0.882 proportion of participants Interval 0.636 to 0.985	—
Proportion Of Complement Inhibitor Treatment-naïve Participants With Complete TMA Response At Week 52 LDH normalization	1.000 proportion of participants Interval 0.805 to 1.0	—
Proportion Of Complement Inhibitor Treatment-naïve Participants With Complete TMA Response At Week 52 ≥25% improvement in serum creatinine from baseline	1.000 proportion of participants Interval 0.805 to 1.0	—

SECONDARY outcome

Timeframe: Week 26 and Week 52

For participants requiring dialysis within 5 days prior to ALXN1210 treatment initiation, the number of participants no longer requiring dialysis is reported.

Outcome measures

Outcome measures
Measure	Complement Inhibitor Treatment Naïve n=6 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.	Eculizumab Experienced Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.
Participants Who Do Not Require Dialysis at Weeks 26 and 52 Week 26	5 Participants	0 Participants
Participants Who Do Not Require Dialysis at Weeks 26 and 52 Week 52	6 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Week 26 and Week 52

Population: Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, met pre-specified eligibility criteria, and had evaluable data at the specified timepoint (Week 26 or Week 52). Here, Overall 'Number of Participants Analyzed' signifies those who were evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable for specified categories.

Kidney function evaluated by eGFR was summarized at baseline and the Week 26 and Week 52 time points using descriptive statistics for continuous variables for the observed value, as well as the change from baseline. The baseline value was defined as the average of the values from the assessments performed prior to the first study drug infusion (these could include results from Screening and the Day 1 visit). A value of 10 mL/min/1.73 m\^2 for eGFR was imputed for participants requiring dialysis for acute kidney injury. The observed value and change from baseline are reported in mL/min/1.73 m\^2. An increase indicated improvement in kidney function.

Outcome measures

Outcome measures
Measure	Complement Inhibitor Treatment Naïve n=17 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.	Eculizumab Experienced n=10 Participants Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.
Change From Baseline In eGFR At Weeks 26 and 52 Baseline	22.0 mL/min/1.73 m^2 Interval 10.0 to 84.0	99.75 mL/min/1.73 m^2 Interval 54.0 to 136.5
Change From Baseline In eGFR At Weeks 26 and 52 Change From Baseline at Week 26	80.0 mL/min/1.73 m^2 Interval 0.0 to 222.0	-2.00 mL/min/1.73 m^2 Interval -94.0 to 18.0
Change From Baseline In eGFR At Weeks 26 and 52 Change From Baseline at Week 52	94.0 mL/min/1.73 m^2 Interval 10.0 to 230.0	-3.00 mL/min/1.73 m^2 Interval -20.0 to 9.0

SECONDARY outcome

Timeframe: Baseline, Week 26, and Week 52

Population: Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, met pre-specified eligibility criteria, and had evaluable data at the specified timepoint (Week 26 or Week 52). Here, Overall 'Number of Participants Analyzed' signifies those who were evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable for specified categories.

The CKD stage is presented as the change from baseline in the participants that Improved (excluding those with Stage 1 \[normal renal function\] at baseline as they cannot improve), Worsened (excluding those with Stage 5 at baseline as they cannot worsen), and Stayed the Same, compared to the CKD stage at baseline. Baseline was derived based on the last available eGFR before starting treatment. Stage 5 was considered the worst category, while Stage 1 was considered the best category. A 2-sided 95% CI for the proportion, based on exact confidence limits using the Clopper-Pearson method, was provided for each category. The CKD stage was classified based on the National Kidney Foundation Chronic Kidney Disease Stage.

Outcome measures

Outcome measures
Measure	Complement Inhibitor Treatment Naïve n=17 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.	Eculizumab Experienced n=10 Participants Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.
Participants With Change From Baseline In CKD Stage At Weeks 26 and 52 Week 26, Improved	15 Participants	0 Participants
Participants With Change From Baseline In CKD Stage At Weeks 26 and 52 Week 26, Worsened	0 Participants	3 Participants
Participants With Change From Baseline In CKD Stage At Weeks 26 and 52 Week 26, Stayed the Same	2 Participants	7 Participants
Participants With Change From Baseline In CKD Stage At Weeks 26 and 52 Week 52, Improved	16 Participants	0 Participants
Participants With Change From Baseline In CKD Stage At Weeks 26 and 52 Week 52, Worsened	0 Participants	0 Participants
Participants With Change From Baseline In CKD Stage At Weeks 26 and 52 Week 52, Stayed the Same	0 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline, Week 26 and Week 52

Population: Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, met pre-specified eligibility criteria, and had evaluable data at the specified time point (Week 26 or Week 52). Here, 'Number Analyzed' signifies participants evaluable for specified categories.

The hematologic TMA parameter of platelet count was summarized at baseline and at Week 26 and Week 52 using descriptive statistics for continuous variables for the change from baseline. Results are reported in platelets\*10\^9/liter (L) blood.

Outcome measures

Outcome measures
Measure	Complement Inhibitor Treatment Naïve n=18 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.	Eculizumab Experienced n=10 Participants Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.
Change From Baseline In Platelet Count At Weeks 26 and 52 Baseline	51.25 platelets*10^9/L Interval 14.0 to 125.0	281.75 platelets*10^9/L Interval 207.0 to 415.5
Change From Baseline In Platelet Count At Weeks 26 and 52 Change from Baseline at Week 26	247.00 platelets*10^9/L Interval 57.5 to 368.5	-2.25 platelets*10^9/L Interval -74.5 to 123.5
Change From Baseline In Platelet Count At Weeks 26 and 52 Change from Baseline at Week 52	213.00 platelets*10^9/L Interval 19.5 to 471.5	-34.75 platelets*10^9/L Interval -109.0 to 109.0

SECONDARY outcome

Timeframe: Baseline, Week 26 and Week 52

Population: Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, met pre-specified eligibility criteria, and had evaluable data at the specified timepoint (Week 26 or Week 52). Here, Overall 'Number of Participants Analyzed' signifies those who were evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable for specified categories.

The hematologic TMA parameter of serum LDH was summarized at baseline and at Week 26 and Week 52 using descriptive statistics for continuous variables for the change from baseline. Results are reported in units (U)/L serum.

Outcome measures

Outcome measures
Measure	Complement Inhibitor Treatment Naïve n=17 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.	Eculizumab Experienced n=10 Participants Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.
Change From Baseline In LDH At Weeks 26 and 52 Baseline	1963.00 U/L Interval 772.0 to 4985.0	206.50 U/L Interval 138.5 to 356.0
Change From Baseline In LDH At Weeks 26 and 52 Change From Baseline at Week 26	-1851.50 U/L Interval -4713.0 to -513.0	-8.50 U/L Interval -50.5 to 50.5
Change From Baseline In LDH At Weeks 26 and 52 Change From Baseline at Week 52	-1825.50 U/L Interval -4724.0 to -579.0	-17.50 U/L Interval -34.5 to 29.5

SECONDARY outcome

Timeframe: Baseline, Week 26 and Week 52

Population: Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, met pre-specified eligibility criteria, and had evaluable data at the specified timepoint (Week 26 or Week 52). Here, 'Number Analyzed' signifies participants evaluable for specified categories.

The hematologic TMA parameter of hemoglobin level was summarized at baseline and at Week 26 and Week 52 using descriptive statistics for continuous variables for the change from baseline. Results are reported in grams (g)/L blood.

Outcome measures

Outcome measures
Measure	Complement Inhibitor Treatment Naïve n=18 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.	Eculizumab Experienced n=10 Participants Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.
Change From Baseline In Hemoglobin At Weeks 26 and 52 Baseline	74.25 g/L Interval 32.0 to 106.0	132.00 g/L Interval 114.5 to 148.0
Change From Baseline In Hemoglobin At Weeks 26 and 52 Change From Baseline at Week 26	46.50 g/L Interval 26.5 to 86.0	-3.50 g/L Interval -19.5 to 8.0
Change From Baseline In Hemoglobin At Weeks 26 and 52 Change From Baseline at Week 52	51.50 g/L Interval -19.0 to 80.0	5.50 g/L Interval -7.5 to 13.5

SECONDARY outcome

Timeframe: Baseline through Week 26 and through Week 52

Population: Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, met pre-specified eligibility criteria, and had evaluable data at the specified timepoints (Week 26 or Week 52). Here, Overall 'Number of Participants Analyzed' signifies those who were evaluable for this outcome measure.

The percentage of participants with an increase from baseline in hemoglobin ≥20 g/L, observed at 2 separate assessments obtained at least 4 weeks (28 days) apart, and any measurement in between, was assessed through Week 26 and Week 52 and is presented as the percentage of responders, along with a 2-sided 95% CI. The 95% CIs are based on exact confidence limits using the Clopper-Pearson method. To be considered a responder during the 26-week and 52-week Extension Periods, the latest time point a participant could first meet the response criteria was 28 days before the respective Week 26 and Week 52 assessments (components of the response maintained for at least 28 days).

Outcome measures

Outcome measures
Measure	Complement Inhibitor Treatment Naïve n=17 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.	Eculizumab Experienced Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.
Percentage Of Complement Inhibitor Treatment-naïve Participants With An Increase From Baseline In Hemoglobin ≥20 g/L Through Week 26 and Week 52 Week 26	100 percentage of participants Interval 80.5 to 100.0	—
Percentage Of Complement Inhibitor Treatment-naïve Participants With An Increase From Baseline In Hemoglobin ≥20 g/L Through Week 26 and Week 52 Week 52	94.1 percentage of participants Interval 71.3 to 99.9	—

SECONDARY outcome

Timeframe: Baseline, Week 26 and Week 52

Population: Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, met pre-specified eligibility criteria, and had evaluable data at the specified timepoint (Week 26 or Week 52). Here, Overall 'Number of Participants Analyzed' signifies those who were evaluable for this outcome measure.

Quality of life was assessed in participants \>5 years of age by the Pediatric FACIT-Fatigue Questionnaire (reported by participants who were ≥8 years of age at the time of enrollment; caregiver reported or caregiver assistance for participants who were 5 to \<8 years of age at the time of enrollment). The FACIT Fatigue data were summarized at baseline and each post baseline time point using descriptive statistics for continuous variables for the observed value as well as the change from baseline. The FACIT Fatigue Version 4 questionnaire at baseline and each post-infusion time point was scored using standard scoring algorithms. The score ranges from 0 to 52, with a higher score indicating less fatigue. An increase in score indicated an improvement in quality of life.

Outcome measures

Outcome measures
Measure	Complement Inhibitor Treatment Naïve n=9 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.	Eculizumab Experienced n=8 Participants Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.
Change From Baseline In Quality Of Life As Measured By The Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Version 4 Questionnaire (Participants ≥5 Years Of Age) At Weeks 26 and 52 Change From Baseline at Week 52	9.00 units on a scale Interval 3.0 to 47.0	-1.00 units on a scale Interval -7.0 to 2.0
Change From Baseline In Quality Of Life As Measured By The Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Version 4 Questionnaire (Participants ≥5 Years Of Age) At Weeks 26 and 52 Baseline	35.00 units on a scale Interval 4.0 to 44.0	50.00 units on a scale Interval 42.0 to 52.0
Change From Baseline In Quality Of Life As Measured By The Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Version 4 Questionnaire (Participants ≥5 Years Of Age) At Weeks 26 and 52 Change From Baseline at Week 26	10.00 units on a scale Interval 4.0 to 48.0	0.00 units on a scale Interval -5.0 to 3.0

Adverse Events

Complement Inhibitor Treatment Naïve

Serious events: 16 serious events

Other events: 21 other events

Deaths: 0 deaths

Eculizumab Experienced

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Alexion Pharmaceuticals Inc.

Phone: 855-752-2356

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Complement Inhibitor Treatment Naïve n=24 participants at risk Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.	Eculizumab Experienced n=10 participants at risk Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.
Infections and infestations Gastroenteritis viral	8.3% 2/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Infections and infestations Bronchitis	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	10.0% 1/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Infections and infestations Cytomegalovirus enteritis	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Infections and infestations Escherichia bacteraemia	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Infections and infestations Escherichia pyelonephritis	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Infections and infestations Gastroenteritis	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Infections and infestations Gastroenteritis rotavirus	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Infections and infestations Human bocavirus infection	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Infections and infestations Pharyngitis	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Infections and infestations Pneumonia	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	10.0% 1/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Infections and infestations Viral infection	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Infections and infestations Viral pharyngitis	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Gastrointestinal disorders Abdominal pain	8.3% 2/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Gastrointestinal disorders Diarrhoea	12.5% 3/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Gastrointestinal disorders Pancreatitis	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Gastrointestinal disorders Vomiting	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Nervous system disorders Headache	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Nervous system disorders Posterior reversible encephalopathy syndrome	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Vascular disorders Hypertension	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Blood and lymphatic system disorders Anaemia	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Congenital, familial and genetic disorders Atrial septal defect	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
General disorders Pyrexia	16.7% 4/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Injury, poisoning and procedural complications Subdural haematoma	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Metabolism and nutrition disorders Decreased appetite	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Musculoskeletal and connective tissue disorders Myalgia	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Infections and infestations Upper respiratory tract infection	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	10.0% 1/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Vascular disorders Hypertensive urgency	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Renal and urinary disorders Glomerulonephritis membranoproliferative	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Renal and urinary disorders Proteinuria	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
Musculoskeletal and connective tissue disorders Juvenile idiopathic arthritis	4.2% 1/24 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).	0.00% 0/10 • From the beginning of the initial evaluation period (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).