Trial Outcomes & Findings for A Study of Ravulizumab (ALXN1210) in Children and Adolescents With Paroxysmal Nocturnal Hemoglobinuria (NCT NCT03406507)

NCT ID: NCT03406507

Last Updated: 2023-03-27

Results Overview

Blood samples for determination of ravulizumab Cmax were collected before and after administration of study drug at designated time points. Results are reported in micrograms/milliliter (μg/mL).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 13 participants
• Primary outcome timeframe: Week 1 (Day 1), Week 2 (Day 15), Week 10 (Day 71), and Week 18 (Day 127)
• Results posted on: 2023-03-27

Participant Flow

Thirteen participants, from birth to < 18 years, were planned to be enrolled to ensure at least 10 evaluable participants would complete the 26-week Primary Evaluation Period. Participants were recruited from 9 sites across 6 countries (United States, United Kingdom, France, Netherlands, Russia, and Norway).

Participant milestones

Measure	Treatment Naïve Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab Experienced Eculizumab-experienced participants received weight-based doses of ravulizumab.
Primary Evaluation Period STARTED	5	8
Primary Evaluation Period Received at Least 1 Dose of Study Drug	5	8
Primary Evaluation Period COMPLETED	5	8
Primary Evaluation Period NOT COMPLETED	0	0
Extension Period STARTED	5	8
Extension Period Received at Least 1 Dose of Study Drug	5	8
Extension Period COMPLETED	5	7
Extension Period NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Treatment Naïve Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab Experienced Eculizumab-experienced participants received weight-based doses of ravulizumab.
Extension Period Lack of Efficacy	0	1

Baseline Characteristics

A Study of Ravulizumab (ALXN1210) in Children and Adolescents With Paroxysmal Nocturnal Hemoglobinuria

Baseline characteristics by cohort

Measure	Treatment Naïve n=5 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab Experienced n=8 Participants Eculizumab-experienced participants received weight-based doses of ravulizumab.	Total n=13 Participants Total of all reporting groups
Age, Continuous	14.4 years STANDARD_DEVIATION 2.19 • n=5 Participants	14.4 years STANDARD_DEVIATION 3.07 • n=7 Participants	14.4 years STANDARD_DEVIATION 2.66 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Race - Undisclosed	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity - Undisclosed	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 1 (Day 1), Week 2 (Day 15), Week 10 (Day 71), and Week 18 (Day 127)

Population: Pharmacokinetic (PK): Participants enrolled into the study who received at least 1 dose of ravulizumab and who had evaluable interim PK data. The PK set was used for all PK analyses.

Blood samples for determination of ravulizumab Cmax were collected before and after administration of study drug at designated time points. Results are reported in micrograms/milliliter (μg/mL).

Outcome measures

Measure	Treatment Naïve n=5 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab Experienced n=8 Participants Eculizumab-experienced participants received weight-based doses of ravulizumab.
Maximum Observed Serum Concentration (Cmax) Of Ravulizumab Day 1: End of Infusion	725.40 μg/mL Standard Deviation 93.730	884.63 μg/mL Standard Deviation 170.842
Maximum Observed Serum Concentration (Cmax) Of Ravulizumab Day 15: End of Infusion	1161.60 μg/mL Standard Deviation 254.348	1612.50 μg/mL Standard Deviation 211.441
Maximum Observed Serum Concentration (Cmax) Of Ravulizumab Day 71: End of Infusion	1402.00 μg/mL Standard Deviation 344.267	1581.43 μg/mL Standard Deviation 207.961
Maximum Observed Serum Concentration (Cmax) Of Ravulizumab Day 127: End of Infusion	1396.00 μg/mL Standard Deviation 403.770	1705.00 μg/mL Standard Deviation 164.751

PRIMARY outcome

Timeframe: Week 2 (Day 15), Week 10 (Day 71), Week 18 (Day 127), Week 26 (Day 183)

Population: Pharmacokinetic (PK): participants enrolled into the study who received at least 1 dose of ravulizumab and who had evaluable interim PK data. The PK set was used for all PK analyses.

Blood samples for determination of ravulizumab Ctrough were collected before and after administration of study drug at designated time points. Trough serum concentration was measured at end of dosing interval at steady state. Results are reported in μg/mL.

Outcome measures

Measure	Treatment Naïve n=5 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab Experienced n=8 Participants Eculizumab-experienced participants received weight-based doses of ravulizumab.
Trough Serum Concentration (Ctrough) Of Ravulizumab Day 127: Predose	410.80 μg/mL Standard Deviation 215.503	554.88 μg/mL Standard Deviation 60.976
Trough Serum Concentration (Ctrough) Of Ravulizumab Day 183: Predose	419.00 μg/mL Standard Deviation 191.921	565.63 μg/mL Standard Deviation 68.980
Trough Serum Concentration (Ctrough) Of Ravulizumab Day 15: Predose	358.20 μg/mL Standard Deviation 51.978	452.25 μg/mL Standard Deviation 68.312
Trough Serum Concentration (Ctrough) Of Ravulizumab Day 71: Predose	370.20 μg/mL Standard Deviation 134.267	521.00 μg/mL Standard Deviation 72.870

PRIMARY outcome

Timeframe: Week 18

Population: Pharmacokinetic (PK): participants enrolled into the study who received at least 1 dose of ravulizumab and who had evaluable interim PK data. The PK set was used for all PK analyses.

Blood samples for determination of ravulizumab accumulation ratio for Cmax were collected before and after administration of study drug at designated time points. The accumulation ratio was calculated as Cmax from the last maintenance dose (Week 18) divided by Cmax from the first maintenance dose (Week 2).

Outcome measures

Measure	Treatment Naïve n=5 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab Experienced n=8 Participants Eculizumab-experienced participants received weight-based doses of ravulizumab.
Mean Accumulation Ratio For Cmax Of Ravulizumab Following The Last Maintenance Dose Relative To The First Maintenance Dose	1.1995 Ratio Standard Deviation 0.21038	1.0630 Ratio Standard Deviation 0.06872

PRIMARY outcome

Timeframe: Week 18

Population: Pharmacokinetic (PK): participants enrolled into the study who received at least 1 dose of ravulizumab and who had evaluable interim PK data. The PK set was used for all PK analyses.

Blood samples for determination of ravulizumab accumulation ratio for Ctrough were collected before and after administration of study drug at designated time points. The accumulation ratio was calculated as Ctrough from the last maintenance dose (Week 18) divided by Ctrough from the first maintenance dose (Week 2).

Outcome measures

Measure	Treatment Naïve n=4 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab Experienced n=8 Participants Eculizumab-experienced participants received weight-based doses of ravulizumab.
Mean Accumulation Ratio For Ctrough Of Ravulizumab Following The Last Maintenance Dose Relative To The First Maintenance Dose	1.2208 Ratio Standard Deviation 0.32490	1.0700 Ratio Standard Deviation 0.09089

PRIMARY outcome

Timeframe: Baseline, Weeks 2, 10, 18, and 26 (end of infusion)

Population: Pharmacodynamic: all participants who received at least 1 dose of ravulizumab and who had evaluable pharmacodynamic data.

Blood samples for determination of free C5 were collected before and after administration of study drug at designated time points.

Outcome measures

Measure	Treatment Naïve n=5 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab Experienced n=8 Participants Eculizumab-experienced participants received weight-based doses of ravulizumab.
Change In Free Complement Component C5 (C5) Concentrations Over Time Week 2	-105.319 ug/mL Standard Deviation 17.1118	0.000 ug/mL Standard Deviation 0.0000
Change In Free Complement Component C5 (C5) Concentrations Over Time Week 10	-105.310 ug/mL Standard Deviation 17.1139	0.003 ug/mL Standard Deviation 0.0052
Change In Free Complement Component C5 (C5) Concentrations Over Time Week 18	-105.320 ug/mL Standard Deviation 17.1165	0.006 ug/mL Standard Deviation 0.0067
Change In Free Complement Component C5 (C5) Concentrations Over Time Week 26	-105.320 ug/mL Standard Deviation 17.1184	0.006 ug/mL Standard Deviation 0.0070

PRIMARY outcome

Timeframe: Baseline, Weeks 2, 10, 18, and 26

Population: Pharmacodynamic: all participants who received at least 1 dose of ravulizumab and who had evaluable pharmacodynamic data.

Blood samples for determination of cRBC hemolytic activity were collected before and after administration of study drug at designated time points.

Outcome measures

Measure	Treatment Naïve n=5 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab Experienced n=8 Participants Eculizumab-experienced participants received weight-based doses of ravulizumab.
Change In Chicken Red Blood Cell (cRBC) Hemolytic Activity Over Time Week 2	-93.12 percentage of hemolysis Standard Deviation 9.259	1.95 percentage of hemolysis Standard Deviation 2.816
Change In Chicken Red Blood Cell (cRBC) Hemolytic Activity Over Time Week 10	-93.24 percentage of hemolysis Standard Deviation 9.241	3.97 percentage of hemolysis Standard Deviation 9.209
Change In Chicken Red Blood Cell (cRBC) Hemolytic Activity Over Time Week 18	-96.93 percentage of hemolysis Standard Deviation 4.543	2.78 percentage of hemolysis Standard Deviation 5.673
Change In Chicken Red Blood Cell (cRBC) Hemolytic Activity Over Time Week 26	-96.78 percentage of hemolysis Standard Deviation 4.816	7.03 percentage of hemolysis Standard Deviation 12.680

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: Full Analysis: all participants who received at least 1 dose of ravulizumab and had at least 1 efficacy assessment after the first infusion of ravulizumab.

Blood and urine samples for determination of LDH levels were collected at designated time points. Baseline was defined as the average of all assessments analyzed by the central laboratory prior to first study drug administration.

Outcome measures

Measure	Treatment Naïve n=5 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab Experienced n=8 Participants Eculizumab-experienced participants received weight-based doses of ravulizumab.
Percentage Change From Baseline At Week 26 In Lactate Dehydrogenase (LDH) Levels	-47.91 Percent Change Standard Deviation 52.716	4.65 Percent Change Standard Deviation 44.702

SECONDARY outcome

Timeframe: Week 26

Population: Full Analysis: all participants who received at least 1 dose of ravulizumab and had at least 1 efficacy assessment after the first infusion of ravulizumab.

Transfusion avoidance was defined as the proportion of participants who remained transfusion-free and did not require a transfusion according to protocol-specified guidelines. Point estimates and 2-sided 95% exact confidence intervals (CIs) were computed. Participants who withdrew from the study due to lack of efficacy during the Primary Evaluation Period were considered as non-responders and were counted in the group needing transfusion. For participants who withdrew from the study for any other reason during the Primary Evaluation Period, their data up to the time of withdrawal was used to assess TA.

Outcome measures

Measure	Treatment Naïve n=5 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab Experienced n=8 Participants Eculizumab-experienced participants received weight-based doses of ravulizumab.
Percentage Of Participants Who Achieved Transfusion Avoidance (TA)	60.00 Percentage of Participants Interval 14.66 to 94.73	100.00 Percentage of Participants Interval 63.06 to 100.0

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: Full Analysis: all participants who received at least 1 dose of ravulizumab and had at least 1 efficacy assessment after the first infusion of ravulizumab.

Quality of life was measured by Pediatric Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Questionnaire (participants ≥ 5 years of age), a 13-item questionnaire that assesses fatigue and its impact upon daily activities and function over the preceding 7 days. Each item is scored on a 5-point scale, and total scores range from 0 to 52, with a higher score indicating better QoL. The scoring guideline for the Pediatric FACIT-Fatigue instrument was used to calculate a FACIT-Fatigue score. Changes from baseline in FACIT-Fatigue scores were summarized at baseline and at the study visits where this assessment was collected up to Day 183 (Week 26). At each study visit, the proportion of participants who showed an improvement of at least 3 points for the Pediatric FACIT-Fatigue scores were summarized by point estimates and 2-sided 95% exact CIs.

Outcome measures

Measure	Treatment Naïve n=5 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab Experienced n=8 Participants Eculizumab-experienced participants received weight-based doses of ravulizumab.
Change In Quality Of Life (QoL) From Baseline To Week 26	3.40 units on a scale Standard Deviation 6.107	1.28 units on a scale Standard Deviation 5.235

SECONDARY outcome

Timeframe: Week 26

Population: Full Analysis: all participants who received at least 1 dose of ravulizumab and had at least 1 efficacy assessment after the first infusion of ravulizumab.

Stabilized hemoglobin was defined as avoidance of a ≥ 2 g/dL decrease in hemoglobin level from baseline in the absence of transfusion through Week 26. Point estimates and 2-sided 95% exact CIs were computed. Participants who withdrew from the study due to lack of efficacy during the Primary Evaluation Period were considered as non-responders and were counted in the group who did not meet the stabilized hemoglobin definition. For participants who withdrew from the study for any other reason during the Primary Evaluation Period, their data up to the time of withdrawal were used to assess stabilized hemoglobin.

Outcome measures

Measure	Treatment Naïve n=5 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab Experienced n=8 Participants Eculizumab-experienced participants received weight-based doses of ravulizumab.
Percentage Of Participants With Stabilized Hemoglobin At Week 26	60.0 Percentage of Participants Interval 14.66 to 94.73	75.0 Percentage of Participants Interval 34.91 to 96.81

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: Full Analysis: all participants who received at least 1 dose of ravulizumab and had at least 1 efficacy assessment after the first infusion of ravulizumab.

Percentage change from baseline in free hemoglobin was summarized at all study visits up to Day 183 (Week 26). Baseline was defined as the last non-missing assessment value prior to the first study drug infusion.

Outcome measures

Measure	Treatment Naïve n=5 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab Experienced n=8 Participants Eculizumab-experienced participants received weight-based doses of ravulizumab.
Percentage Change In Free Hemoglobin From Baseline To Week 26	87.32 Percentage Change Standard Deviation 226.816	-15.29 Percentage Change Standard Deviation 71.780

SECONDARY outcome

Timeframe: Week 26

Population: Full Analysis: all participants who received at least 1 dose of ravulizumab and had at least 1 efficacy assessment after the first infusion of ravulizumab.

Breakthrough hemolysis was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia, major adverse vascular event [including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH as follows: for participants who entered the study naïve to complement inhibitor treatment, elevated LDH ≥ 2 × the upper limit of normal (ULN) after prior LDH reduction to < 1.5 × ULN on therapy; for participants who entered the study stabilized on eculizumab treatment, elevated LDH ≥ 2 × ULN. Participants who withdrew from the study due to lack of efficacy during the Primary Evaluation Period were considered as non-responders and were counted in the group with BTH. For participants who withdrew from the study for any other reason during the Primary Evaluation Period, their data up to the time of withdrawal were used to assess BTH. No participants experienced BTH.

Outcome measures

Measure	Treatment Naïve n=5 Participants Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab Experienced n=8 Participants Eculizumab-experienced participants received weight-based doses of ravulizumab.
Percentage Of Participants With Breakthrough Hemolysis (BTH) At Week 26	0 Participants	0 Participants

Adverse Events

Treatment Naïve

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Eculizumab Experienced

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	Treatment Naïve n=5 participants at risk Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab Experienced n=8 participants at risk Eculizumab-experienced participants received weight-based doses of ravulizumab.
General disorders Device related thrombosis	20.0% 1/5 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)	0.00% 0/8 • Day 1 through End of Study (Up to Day 1610)
General disorders Multiple organ dysfunction syndrome	20.0% 1/5 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)	0.00% 0/8 • Day 1 through End of Study (Up to Day 1610)
Infections and infestations Device related sepsis	20.0% 1/5 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)	0.00% 0/8 • Day 1 through End of Study (Up to Day 1610)
Infections and infestations Septic shock	20.0% 1/5 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)	0.00% 0/8 • Day 1 through End of Study (Up to Day 1610)
Infections and infestations Staphylococcal infection	20.0% 1/5 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)	0.00% 0/8 • Day 1 through End of Study (Up to Day 1610)
Infections and infestations Viral upper respiratory tract infection	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Blood and lymphatic system disorders Aplastic anaemia	20.0% 1/5 • Number of events 2 • Day 1 through End of Study (Up to Day 1610)	0.00% 0/8 • Day 1 through End of Study (Up to Day 1610)
Blood and lymphatic system disorders Breakthrough haemolysis	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Infections and infestations Influenza	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)

Other adverse events

Measure	Treatment Naïve n=5 participants at risk Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab.	Eculizumab Experienced n=8 participants at risk Eculizumab-experienced participants received weight-based doses of ravulizumab.
Ear and labyrinth disorders Ear pain	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 2 • Day 1 through End of Study (Up to Day 1610)
Endocrine disorders Cushing's syndrome	20.0% 1/5 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)	0.00% 0/8 • Day 1 through End of Study (Up to Day 1610)
Gastrointestinal disorders Abdominal pain	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	37.5% 3/8 • Number of events 3 • Day 1 through End of Study (Up to Day 1610)
Gastrointestinal disorders Constipation	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	25.0% 2/8 • Number of events 2 • Day 1 through End of Study (Up to Day 1610)
Gastrointestinal disorders Dysphagia	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Gastrointestinal disorders Nausea	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	37.5% 3/8 • Number of events 3 • Day 1 through End of Study (Up to Day 1610)
Gastrointestinal disorders Vomiting	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 2 • Day 1 through End of Study (Up to Day 1610)
General disorders Fatigue	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	25.0% 2/8 • Number of events 2 • Day 1 through End of Study (Up to Day 1610)
General disorders Pyrexia	20.0% 1/5 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Immune system disorders Serum sickness	20.0% 1/5 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)	0.00% 0/8 • Day 1 through End of Study (Up to Day 1610)
Infections and infestations Nasopharyngitis	20.0% 1/5 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)	25.0% 2/8 • Number of events 2 • Day 1 through End of Study (Up to Day 1610)
Infections and infestations Cystitis	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 4 • Day 1 through End of Study (Up to Day 1610)
Infections and infestations Hordeolum	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Infections and infestations Paronychia	20.0% 1/5 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)	0.00% 0/8 • Day 1 through End of Study (Up to Day 1610)
Infections and infestations Pharyngitis	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 2 • Day 1 through End of Study (Up to Day 1610)
Infections and infestations Rhinitis	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Infections and infestations Sinusitis	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Infections and infestations Upper respiratory tract infection	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	25.0% 2/8 • Number of events 3 • Day 1 through End of Study (Up to Day 1610)
Infections and infestations Urinary tract infection	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	25.0% 2/8 • Number of events 2 • Day 1 through End of Study (Up to Day 1610)
Injury, poisoning and procedural complications Electric shock	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Injury, poisoning and procedural complications Sunburn	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Injury, poisoning and procedural complications Wound	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Investigations Blood pressure increased	20.0% 1/5 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)	0.00% 0/8 • Day 1 through End of Study (Up to Day 1610)
Metabolism and nutrition disorders Decreased appetite	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Musculoskeletal and connective tissue disorders Arthralgia	20.0% 1/5 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)	0.00% 0/8 • Day 1 through End of Study (Up to Day 1610)
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 3 • Day 1 through End of Study (Up to Day 1610)
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	25.0% 2/8 • Number of events 2 • Day 1 through End of Study (Up to Day 1610)
Nervous system disorders Headache	20.0% 1/5 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)	25.0% 2/8 • Number of events 3 • Day 1 through End of Study (Up to Day 1610)
Nervous system disorders Dizziness	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	25.0% 2/8 • Number of events 2 • Day 1 through End of Study (Up to Day 1610)
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Blood and lymphatic system disorders Anaemia	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	25.0% 2/8 • Number of events 5 • Day 1 through End of Study (Up to Day 1610)
Gastrointestinal disorders Diarrhoea	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	25.0% 2/8 • Number of events 2 • Day 1 through End of Study (Up to Day 1610)
Gastrointestinal disorders Rectal hemorrhage	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 2 • Day 1 through End of Study (Up to Day 1610)
Hepatobiliary disorders Hyperbilirubinemia	20.0% 1/5 • Number of events 3 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Vascular disorders Hematoma	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Gastrointestinal disorders Abdominal pain upper	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	37.5% 3/8 • Number of events 3 • Day 1 through End of Study (Up to Day 1610)
Infections and infestations COVID-19	40.0% 2/5 • Number of events 2 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Infections and infestations Ear infection	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Infections and infestations Infected bite	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Infections and infestations Respiratory tract infection viral	20.0% 1/5 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)	0.00% 0/8 • Day 1 through End of Study (Up to Day 1610)
Infections and infestations Viral infection	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Infections and infestations Viral upper respiratory tract infection	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Injury, poisoning and procedural complications Tooth fracture	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Injury, poisoning and procedural complications Toxicity to various agents	20.0% 1/5 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)	0.00% 0/8 • Day 1 through End of Study (Up to Day 1610)
Injury, poisoning and procedural complications Transfusion reaction	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Investigations Blood bilirubin increased	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Investigations Blood creatinine increased	20.0% 1/5 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)	0.00% 0/8 • Day 1 through End of Study (Up to Day 1610)
Metabolism and nutrition disorders Iron deficiency	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 2 • Day 1 through End of Study (Up to Day 1610)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 2 • Day 1 through End of Study (Up to Day 1610)
Musculoskeletal and connective tissue disorders Juvenile idiopathic arthritis	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Musculoskeletal and connective tissue disorders Kyphosis	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Skin and subcutaneous tissue disorders Acne	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Skin and subcutaneous tissue disorders In growing nail	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Blood and lymphatic system disorders Aplastic anaemia	20.0% 1/5 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)	0.00% 0/8 • Day 1 through End of Study (Up to Day 1610)
Blood and lymphatic system disorders Lymphadenitis	20.0% 1/5 • Number of events 2 • Day 1 through End of Study (Up to Day 1610)	0.00% 0/8 • Day 1 through End of Study (Up to Day 1610)
Blood and lymphatic system disorders Thrombocytopenia	20.0% 1/5 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)	0.00% 0/8 • Day 1 through End of Study (Up to Day 1610)
General disorders Administration site pain	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Hepatobiliary disorders Cholelithiasis	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Vascular disorders Pallor	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/1 • Day 1 through End of Study (Up to Day 1610)	14.3% 1/7 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
General disorders Asthenia	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
General disorders Catheter site pain	20.0% 1/5 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)	0.00% 0/8 • Day 1 through End of Study (Up to Day 1610)
General disorders Chest pain	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
General disorders Non-cardiac chest pain	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)
Congenital, familial and genetic disorders Chromosomal deletion	0.00% 0/5 • Day 1 through End of Study (Up to Day 1610)	12.5% 1/8 • Number of events 1 • Day 1 through End of Study (Up to Day 1610)

Additional Information

Alexion Pharmaceuticals, Inc.

Alexion Pharmaceuticals, Inc.

Phone: 1.855.752.2356

Email: clinicaltrials@alexion.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place