A Study of Ravulizumab (ALXN1210) in Children and Adolescents With Paroxysmal Nocturnal Hemoglobinuria
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ClinicalTrials.gov Identifier: NCT03406507 |
Recruitment Status :
Active, not recruiting
First Posted : January 23, 2018
Results First Posted : May 9, 2022
Last Update Posted : May 9, 2022
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Condition or disease | Intervention/treatment | Phase |
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Paroxysmal Nocturnal Hemoglobinuria | Biological: Ravulizumab | Phase 3 |
The study consists of a 4-week Screening Period, a 26-week Primary Evaluation Period, and an Extension Period of up to 4 years (with the exception of any country-specific mandates), whichever occurs first.
Efficacy and safety data are reported for the 26-week Primary Evaluation Period only. Analyses were conducted separately for complement inhibitor treatment-naïve participants and eculizumab-experienced participants.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 13 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 3, Open-Label Study of ALXN1210 in Children and Adolescents With Paroxysmal Nocturnal Hemoglobinuria (PNH) |
Actual Study Start Date : | February 22, 2018 |
Actual Primary Completion Date : | March 25, 2020 |
Estimated Study Completion Date : | June 30, 2025 |

Arm | Intervention/treatment |
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Experimental: Ravulizumab
Complement inhibitor treatment-naïve and eculizumab-experienced participants received ravulizumab.
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Biological: Ravulizumab
Single intravenous (IV) loading dose on Day 1, followed by regular IV maintenance dosing beginning on Day 15, based on weight.
Other Names:
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- Maximum Observed Serum Concentration (Cmax) Of Ravulizumab [ Time Frame: Week 1 (Day 1), Week 2 (Day 15), Week 10 (Day 71), and Week 18 (Day 127) ]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).
- Trough Serum Concentration (Ctrough) Of Ravulizumab [ Time Frame: Week 2 (Day 15), Week 10 (Day 71), Week 18 (Day 127), Week 26 (Day 183) ]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.
- Mean Accumulation Ratio For Cmax Of Ravulizumab Following The Last Maintenance Dose Relative To The First Maintenance Dose [ Time Frame: Week 18 ]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).
- Change In Free Complement Component C5 (C5) Concentrations Over Time [ Time Frame: Baseline, Weeks 2, 10, 18, and 26 (end of infusion) ]Blood samples for determination of free C5 were collected before and after administration of study drug at designated time points.
- Change In Chicken Red Blood Cell (cRBC) Hemolytic Activity Over Time [ Time Frame: Baseline, Weeks 2, 10, 18, and 26 ]Blood samples for determination of cRBC hemolytic activity were collected before and after administration of study drug at designated time points.
- Mean Accumulation Ratio For Ctrough Of Ravulizumab Following The Last Maintenance Dose Relative To The First Maintenance Dose [ Time Frame: Week 18 ]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).
- Percentage Change From Baseline At Week 26 In Lactate Dehydrogenase (LDH) Levels [ Time Frame: Baseline, Week 26 ]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.
- Percentage Of Participants Who Achieved Transfusion Avoidance (TA) [ Time Frame: Week 26 ]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.
- Change In Quality Of Life (QoL) From Baseline To Week 26 [ Time Frame: Baseline, Week 26 ]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.
- Percentage Of Participants With Stabilized Hemoglobin At Week 26 [ Time Frame: Week 26 ]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.
- Percentage Change In Free Hemoglobin From Baseline To Week 26 [ Time Frame: Baseline, Week 26 ]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.
- Percentage Of Participants With Breakthrough Hemolysis (BTH) At Week 26 [ Time Frame: Week 26 ]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.

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Ages Eligible for Study: | up to 17 Years (Child) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Participants from birth up to <18 years of age and weighing ≥ 5 kilograms at the time of consent.
- PNH diagnosis confirmed by documented high-sensitivity flow cytometry.
- Presence of 1 or more of the following PNH-related signs or symptoms within 3 months of Screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), anemia, history of a major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction; or history of packed red blood cell transfusion due to PNH.
- Lactate dehydrogenase (LDH) level ≥ 1.5 × upper limit of normal (ULN) for participants not being treated with eculizumab at screening and LDH level ≤ 1.5 × ULN for participants taking eculizumab.
- Documented meningococcal vaccination not more than 3 years prior to dosing, and vaccination against Streptococcus pneumoniae and Haemophilus influenzae.
- Female participants of childbearing potential must use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.
Exclusion Criteria:
- History of bone marrow transplantation.
- History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the investigator or sponsor, would preclude participation.
- Unstable medical conditions (for example, myocardial ischemia, active gastrointestinal bleed, severe congestive heart failure, anticipated need for major surgery within 6 months of randomization, coexisting chronic anemia unrelated to PNH).
- Females who are pregnant or breastfeeding or who have a positive pregnancy test at screening or Day 1.
- Participation in another interventional clinical study or use of any experimental therapy within 30 days before initiation of study drug on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03406507
United States, Georgia | |
Clinical Trial Site | |
Atlanta, Georgia, United States, 30329 | |
United States, Wisconsin | |
Clinical Trial Site | |
Milwaukee, Wisconsin, United States, 53226 | |
France | |
Clinical Trial Site | |
Paris, France | |
Netherlands | |
Clinical Trial Site | |
Utrecht, Netherlands | |
Norway | |
Clinical Trial Site | |
Oslo, Norway | |
Russian Federation | |
Clinical Trial Site | |
Moscow, Russian Federation | |
Clinical Trial Site | |
Saint Petersburg, Russian Federation | |
United Kingdom | |
Clinical Trial Site | |
Leeds, United Kingdom | |
Clinical Trial Site | |
London, United Kingdom |
Documents provided by Alexion Pharmaceuticals:
Responsible Party: | Alexion Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT03406507 |
Other Study ID Numbers: |
ALXN1210-PNH-304 2017-002820-26 ( EudraCT Number ) |
First Posted: | January 23, 2018 Key Record Dates |
Results First Posted: | May 9, 2022 |
Last Update Posted: | May 9, 2022 |
Last Verified: | April 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Ravulizumab ALXN1210 Ultomiris Pharmacokinetics Pharmacodynamics |
Hemoglobinuria Hemoglobinuria, Paroxysmal Proteinuria Urination Disorders Urologic Diseases Urological Manifestations Anemia, Hemolytic Anemia |
Hematologic Diseases Myelodysplastic Syndromes Bone Marrow Diseases Ravulizumab Complement Inactivating Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |