Clinical Trials List
Protocol NumberALXN1210-PNH-301
NCT Number(ClinicalTrials.gov Identfier)NCT02946463
Completed
2017-03-15 - 2024-12-31
Phase III
Terminated6
ICD-10D59.5
Paroxysmal nocturnal hemoglobinuria [Marchiafava-Micheli]
ICD-10D59
Acquired hemolytic anemia
ICD-9283.2
Hemoglobinuria due to hemolysis from external causes
A Phase 3, Randomized, Open-Label, Active-Controlled Study of ALXN1210 Versus Eculizumab in Complement Inhibitor-Naïve Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
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Trial Applicant
IQVIA RDS Taiwan Ltd.
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Sponsor
Alexion Pharmaceuticals, Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2026/03/01
Investigators and Locations
Co-Principal Investigator
- 郭景元 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Completed
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- Sin-Syue Li Division of Hematology & Oncology
- Ya-Ting Hsu Division of Hematology & Oncology
- Ya-Ping Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Completed
Audit
None
Co-Principal Investigator
- Che-Hung Lin Division of Hematology & Oncology
- Ching-Chan Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- 王佐輔 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- MING YAO Division of Hematology & Oncology
- Shang-Ju Wu Division of Hematology & Oncology
- HSIN-AN HOU Division of Hematology & Oncology
- Sheng-chieh Chou Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Completed
Audit
None
Condition/Disease
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Objectives
The primary objective of this study is to assess the noninferiority of ALXN1210 compared to eculizumab in adult
patients with PNH who have never been treated with a complement inhibitor.
Noninferiority will be claimed if after 26 weeks of treatment: 1) the lower bound of the 95% confidence interval
(CI) for the difference (ALXN1210-eculizumab) in transfusion avoidance (TA) rate is greater than -20%, and 2)
the lower bound of the 95% CI for the odds ratio of ALXN1210 compared to eculizumab for lactate dehydrogenase
normalization (LDH-N) is greater than 0.39.
Test Drug
ALXN1210
Active Ingredient
ALXN1210
Dosage Form
IV for Infusion
Dosage
10
Endpoints
Efficacy
Coprimary
• Transfusion avoidance (TA), defined as the proportion of patients who remain transfusion-free and do
not require a transfusion as per protocol-specified guidelines through Day 183 (Week 26)
• Hemolysis as directly measured by the normalization of LDH levels (LDH-N) from Day 29 (first
scheduled evaluation status post initiation of maintenance dosing) through Day 183 (Week 26)
Key Secondary (to be tested in a hierarchical manner)
1. Percentage change in LDH from Baseline to Day 183 (Week 26)
2. Change in quality of life (QoL) assessed via the Functional Assessment of Chronic Illness Therapy
(FACIT)-Fatigue Scale, Version 4, from Baseline to Day 183 (Week 26)
3. Proportion of patients with breakthrough hemolysis, 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], major adverse vascular event [MAVE, including
thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥ 2 × ULN, after
prior LDH reduction to < 1.5 × ULN on therapy
4. Proportion of patients with stabilized hemoglobin, defined as avoidance of a ≥ 2 g/dL decrease in
hemoglobin level from baseline in the absence of transfusion through Day 183 (Week 26)
Other Secondary
• Change in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of
Life Questionnaire-Core 30 Scale (QLQ-C30), Version 3.0, from Baseline to Day 183 (Week 26)
• Time to first occurrence of LDH-N
• Total number of units of pRBCs transfused through Day 183 (Week 26)
• Change in clinical manifestations of PNH (fatigue, hemoglobinuria, abdominal pain, shortness of
breath, anemia, dysphagia, and erectile dysfunction) from Baseline to Day 183 (Week 26)
• Proportion of patients experiencing MAVEs through Day 183 (Week 26)
Pharmacokinetic/Pharmacodynamic (PK/PD)
• Change in serum ALXN1210 and eculizumab concentrations over time
• Change in chicken red blood cell (cRBC) hemolytic activity over time (exploratory)
• Change in free complement component 5 (C5) concentrations over time
Exploratory
• Patient-reported PNH symptoms
• Healthcare resource utilization
Safety
The safety and tolerability of ALXN1210 compared with eculizumab will be evaluated by physical examinations,
vital signs, electrocardiograms (ECGs), laboratory assessments, and incidence of adverse events (AEs) and serious
adverse events (SAEs). The proportion of patients who develop antidrug antibodies (ADAs) will also be assessed.
Coprimary
• Transfusion avoidance (TA), defined as the proportion of patients who remain transfusion-free and do
not require a transfusion as per protocol-specified guidelines through Day 183 (Week 26)
• Hemolysis as directly measured by the normalization of LDH levels (LDH-N) from Day 29 (first
scheduled evaluation status post initiation of maintenance dosing) through Day 183 (Week 26)
Key Secondary (to be tested in a hierarchical manner)
1. Percentage change in LDH from Baseline to Day 183 (Week 26)
2. Change in quality of life (QoL) assessed via the Functional Assessment of Chronic Illness Therapy
(FACIT)-Fatigue Scale, Version 4, from Baseline to Day 183 (Week 26)
3. Proportion of patients with breakthrough hemolysis, 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], major adverse vascular event [MAVE, including
thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥ 2 × ULN, after
prior LDH reduction to < 1.5 × ULN on therapy
4. Proportion of patients with stabilized hemoglobin, defined as avoidance of a ≥ 2 g/dL decrease in
hemoglobin level from baseline in the absence of transfusion through Day 183 (Week 26)
Other Secondary
• Change in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of
Life Questionnaire-Core 30 Scale (QLQ-C30), Version 3.0, from Baseline to Day 183 (Week 26)
• Time to first occurrence of LDH-N
• Total number of units of pRBCs transfused through Day 183 (Week 26)
• Change in clinical manifestations of PNH (fatigue, hemoglobinuria, abdominal pain, shortness of
breath, anemia, dysphagia, and erectile dysfunction) from Baseline to Day 183 (Week 26)
• Proportion of patients experiencing MAVEs through Day 183 (Week 26)
Pharmacokinetic/Pharmacodynamic (PK/PD)
• Change in serum ALXN1210 and eculizumab concentrations over time
• Change in chicken red blood cell (cRBC) hemolytic activity over time (exploratory)
• Change in free complement component 5 (C5) concentrations over time
Exploratory
• Patient-reported PNH symptoms
• Healthcare resource utilization
Safety
The safety and tolerability of ALXN1210 compared with eculizumab will be evaluated by physical examinations,
vital signs, electrocardiograms (ECGs), laboratory assessments, and incidence of adverse events (AEs) and serious
adverse events (SAEs). The proportion of patients who develop antidrug antibodies (ADAs) will also be assessed.
Inclution Criteria
Inclusion Criteria:
1. Male or female, 18 years of age or older at the time of consent.
2. Documented diagnosis of PNH, confirmed by high-sensitivity flow cytometry evaluation of red blood
cells (RBCs) and white blood cells (WBCs), with granulocyte or monocyte clone size of ≥ 5%.
3. 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 (hemoglobin < 10 g/dL),
history of a major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction; or
history of pRBC transfusion due to PNH.
4. LDH level ≥ 1.5 × ULN at screening.
5. To reduce the risk of meningococcal infection (Neisseria meningitidis), all patients must be vaccinated
against meningococcal infections within 3 years prior to, or at the time of, initiating study drug. Patients
who initiate study drug treatment less than 2 weeks after receiving a meningococcal vaccine must receive
treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination.
6. Female patients of childbearing potential and male patients with female partners of childbearing potential
must follow protocol-specified guidance for avoiding pregnancy while on treatment and for 8 months after
last dose of study drug.
7. Patients must be willing and able to give written informed consent and to comply with all study visits and
procedures, including the use of any data collection device(s) to directly record patient data.
1. Male or female, 18 years of age or older at the time of consent.
2. Documented diagnosis of PNH, confirmed by high-sensitivity flow cytometry evaluation of red blood
cells (RBCs) and white blood cells (WBCs), with granulocyte or monocyte clone size of ≥ 5%.
3. 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 (hemoglobin < 10 g/dL),
history of a major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction; or
history of pRBC transfusion due to PNH.
4. LDH level ≥ 1.5 × ULN at screening.
5. To reduce the risk of meningococcal infection (Neisseria meningitidis), all patients must be vaccinated
against meningococcal infections within 3 years prior to, or at the time of, initiating study drug. Patients
who initiate study drug treatment less than 2 weeks after receiving a meningococcal vaccine must receive
treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination.
6. Female patients of childbearing potential and male patients with female partners of childbearing potential
must follow protocol-specified guidance for avoiding pregnancy while on treatment and for 8 months after
last dose of study drug.
7. Patients must be willing and able to give written informed consent and to comply with all study visits and
procedures, including the use of any data collection device(s) to directly record patient data.
Exclusion Criteria
Exclusion Criteria:
1. Current or previous treatment with a complement inhibitor.
2. Platelet count < 30,000/mm3 (30 × 109
/L) at Screening.
3. Absolute neutrophil count < 500/µL (0.5 × 109
/L) at Screening.
4. History of bone marrow transplantation.
5. Body weight < 40 kg at Screening.
6. History of N. meningitidis infection.
7. History of unexplained, recurrent infection.
8. Active systemic bacterial, viral, or fungal infection within 14 days prior to study drug administration on
Day 1.
9. Presence of fever ≥ 38°C (100.4°F) within 7 days prior to study drug administration on Day 1.
10. Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody titer).
11. Immunized with a live-attenuated vaccine 1 month prior to study drug administration on Day 1.
12. History of malignancy within 5 years of Screening with the exception of a nonmelanoma skin cancer or
carcinoma in situ of the cervix that has been treated with no evidence of recurrence.
13. History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease (eg, active hepatitis)
that, in the opinion of the Investigator or Sponsor, precludes the patient’s participation in an
investigational clinical trial.
14. Unstable medical conditions (eg, 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) that would make them unlikely to tolerate the requirements of the protocol (eg,
transfusion guidelines).
15. Concomitant use of any of the following medications is prohibited if not on a stable regimen for the time
period indicated below prior to Screening:
• Erythropoietin or immunosuppressants for at least 8 weeks
• Systemic corticosteroids for at least 4 weeks
• Vitamin K antagonists (eg, warfarin) with a stable international normalized ratio (INR) for at least
4 weeks
• Iron supplements or folic acid for at least 4 weeks
• Low-molecular-weight heparin for at least 4 weeks
16. History of hypersensitivity to murine proteins or to any of the study drug excipients (eg, polysorbate 80).
17. Females who plan to become pregnant or are currently pregnant or breastfeeding.
18. Females who have a positive pregnancy test result at Screening or on Day 1.
19. Participation in another interventional treatment 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.
20. Known or suspected history of drug or alcohol abuse or dependence within 1 year prior to the start of
Screening.
21. Known medical or psychological condition(s) or risk factor that, in the opinion of the Investigator, might
interfere with the patient’s full participation in the study, pose any additional risk for the patient, or
confound the assessment of the patient or outcome of the study.
1. Current or previous treatment with a complement inhibitor.
2. Platelet count < 30,000/mm3 (30 × 109
/L) at Screening.
3. Absolute neutrophil count < 500/µL (0.5 × 109
/L) at Screening.
4. History of bone marrow transplantation.
5. Body weight < 40 kg at Screening.
6. History of N. meningitidis infection.
7. History of unexplained, recurrent infection.
8. Active systemic bacterial, viral, or fungal infection within 14 days prior to study drug administration on
Day 1.
9. Presence of fever ≥ 38°C (100.4°F) within 7 days prior to study drug administration on Day 1.
10. Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody titer).
11. Immunized with a live-attenuated vaccine 1 month prior to study drug administration on Day 1.
12. History of malignancy within 5 years of Screening with the exception of a nonmelanoma skin cancer or
carcinoma in situ of the cervix that has been treated with no evidence of recurrence.
13. History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease (eg, active hepatitis)
that, in the opinion of the Investigator or Sponsor, precludes the patient’s participation in an
investigational clinical trial.
14. Unstable medical conditions (eg, 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) that would make them unlikely to tolerate the requirements of the protocol (eg,
transfusion guidelines).
15. Concomitant use of any of the following medications is prohibited if not on a stable regimen for the time
period indicated below prior to Screening:
• Erythropoietin or immunosuppressants for at least 8 weeks
• Systemic corticosteroids for at least 4 weeks
• Vitamin K antagonists (eg, warfarin) with a stable international normalized ratio (INR) for at least
4 weeks
• Iron supplements or folic acid for at least 4 weeks
• Low-molecular-weight heparin for at least 4 weeks
16. History of hypersensitivity to murine proteins or to any of the study drug excipients (eg, polysorbate 80).
17. Females who plan to become pregnant or are currently pregnant or breastfeeding.
18. Females who have a positive pregnancy test result at Screening or on Day 1.
19. Participation in another interventional treatment 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.
20. Known or suspected history of drug or alcohol abuse or dependence within 1 year prior to the start of
Screening.
21. Known medical or psychological condition(s) or risk factor that, in the opinion of the Investigator, might
interfere with the patient’s full participation in the study, pose any additional risk for the patient, or
confound the assessment of the patient or outcome of the study.
The Estimated Number of Participants
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Taiwan
18 participants
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Global
214 participants
