Clinical Trials List
Protocol NumberALXN1210-PNH-201
NCT Number(ClinicalTrials.gov Identfier)NCT02605993
2015-10-30 - 2019-04-27
Phase II
Terminated2
ICD-9283.2
Hemoglobinuria due to hemolysis from external causes
A Phase 2, Open-label, Multiple Ascending Dose Study to Evaluate the Efficacy, Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of ALXN1210 Administered Intravenously to Patients with Paroxysmal Nocturnal Hemoglobinuria
-
Trial Applicant
IQVIA RDS Taiwan Ltd.
-
Sponsor
Alexion Pharmaceuticals, Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- - - Division of General Internal Medicine
- 劉家豪 Division of General Internal Medicine
- MING YAO Division of General Internal Medicine
- Wen-Chien Chou Division of Others -
- CHENG-HONG TSAI Division of General Internal Medicine
- Jih-Luh Tang Division of Hematology & Oncology
- Chieh-Lung Cheng Division of General Internal Medicine
- HSIN-AN HOU Division of Hematology & Oncology
- Sheng-chieh Chou Division of General Internal Medicine
- Tai-Chung Huang Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Completed
Audit
None
Condition/Disease
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Objectives
Primary:
To evaluate the efficacy, safety, and tolerability of multiple doses of ALXN1210 administered intravenously (IV) to
complement inhibitor treatment-naïve patients with PNH
Secondary:
To characterize the pharmacokinetic (PK) and pharmacodynamic (PD) effects of multiple doses of ALXN1210
administered IV to complement inhibitor treatment-naïve patients with PNH
To investigate the immunogenicity of ALXN1210 administered IV to complement inhibitor treatment-naïve patients
with PNH
Test Drug
ALXN1210
Active Ingredient
ALXN1210
Dosage Form
Injection
Dosage
10
Endpoints
Primary Efficacy:
Change in LDH levels from baseline to Day 253
Secondary Efficacy:
Changes in hemolysis-related hematologic parameters: free hemoglobin, haptoglobin, reticulocyte count, PNH red
blood cell clone, and D-dimer
Changes in clinical manifestations: fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction
Exploratory Efficacy:
Change from baseline in the need for blood transfusions
Change from baseline in disease-associated biomarkers (markers of chronic kidney disease; ie, estimated glomerular
filtration rate, spot urine albumin:creatinine ratio, and plasma brain natriuretic peptide for pulmonary hypertension)
Change from baseline in quality of life, assessed via the Functional Assessment of Chronic Illness Therapy
(FACIT)-Fatigue Scale, version 4 and the European Organisation for Research and Treatment of Cancer, Quality of
Life Questionnaire-Core 30 Scale, version 3.0
Change from baseline in major adverse vascular events (MAVEs)
Immunogenicity:
Measurement of antidrug antibodies (ADA)
Pharmacokinetic/Pharmacodynamic:
Changes in serum ALXN1210 concentration over time
Changes in cRBC hemolytic activity
Changes in free and total C5 concentrations
Safety:
Changes from baseline in physical examination assessments and vital signs
Change from baseline in electrocardiogram parameters
Change from baseline in laboratory assessments
Incidence of adverse events (AEs) and serious adverse events (SAEs)
Change in LDH levels from baseline to Day 253
Secondary Efficacy:
Changes in hemolysis-related hematologic parameters: free hemoglobin, haptoglobin, reticulocyte count, PNH red
blood cell clone, and D-dimer
Changes in clinical manifestations: fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction
Exploratory Efficacy:
Change from baseline in the need for blood transfusions
Change from baseline in disease-associated biomarkers (markers of chronic kidney disease; ie, estimated glomerular
filtration rate, spot urine albumin:creatinine ratio, and plasma brain natriuretic peptide for pulmonary hypertension)
Change from baseline in quality of life, assessed via the Functional Assessment of Chronic Illness Therapy
(FACIT)-Fatigue Scale, version 4 and the European Organisation for Research and Treatment of Cancer, Quality of
Life Questionnaire-Core 30 Scale, version 3.0
Change from baseline in major adverse vascular events (MAVEs)
Immunogenicity:
Measurement of antidrug antibodies (ADA)
Pharmacokinetic/Pharmacodynamic:
Changes in serum ALXN1210 concentration over time
Changes in cRBC hemolytic activity
Changes in free and total C5 concentrations
Safety:
Changes from baseline in physical examination assessments and vital signs
Change from baseline in electrocardiogram parameters
Change from baseline in laboratory assessments
Incidence of adverse events (AEs) and serious adverse events (SAEs)
Inclution Criteria
Inclusion Criteria:
1. Male or female patients ≥ 18 years of age
2. PNH diagnosis confirmed by documented high-sensitivity flow cytometry (red blood cells [RBCs] and/or granulocytes)
3. Mean lactate dehydrogenase (LDH) ≥3 × upper limit of normal, based on 2 measurements from separate blood samples
collected at least 1 day apart during screening
4. Willing and able to give written informed consent and comply with the study visit schedule
5. Documented meningococcal vaccination not more than 3 years prior to dosing
6. Female patients who consider themselves postmenopausal must provide evidence at screening of menopause status,
based on a combination of amenorrhea for at least 1 year and increased serum follicle-stimulating hormone level
(> 30 IU/L) on at least 2 occasions (eg, in the absence of hormone replacement therapy, dietary phytoestrogens) or
estradiol concentration < 10 pg/mL.
7. Female patients of childbearing potential must use highly effective contraception as defined below, starting at screening
and continuing until at least 6 months after the last dose of ALXN1210. Highly effective contraceptive methods are as
follows:
a. Combined (estrogen and progestogen) hormonal contraception associated with inhibition of ovulation:
i. Oral
ii. Intravaginal
iii. Transdermal
b. Progesterone-only hormonal contraception associated with inhibition of ovulation
i. Oral
ii. Injectable
iii. Implantable
c. Intrauterine device
d. Intrauterine hormone-releasing system
e. Bilateral tubal occlusion
8. Male patients with a female spouse/partner of childbearing potential or a pregnant or breastfeeding spouse or partner
must agree to use barrier contraception (male condom) during the Treatment Period and for at least 6 months after the
last dose of ALXN1210. Barrier contraception is required even with documented medical assessment of surgical success
of a vasectomy. Female spouses/partners of male patients who are of childbearing potential must use highly effective
contraception (as defined in inclusion criterion #7) or acceptable contraception, as defined below, starting at screening
and continuing until at least 6 months after the last dose of ALXN1210. Male patients must not donate sperm during the
Screening and Treatment Periods and for at least 6 months after the last dose of ALXN1210.
a. Acceptable contraceptive methods are as follows:
i. Simultaneous use of male condom and appropriate barrier methods for the female partner
1. Male or female patients ≥ 18 years of age
2. PNH diagnosis confirmed by documented high-sensitivity flow cytometry (red blood cells [RBCs] and/or granulocytes)
3. Mean lactate dehydrogenase (LDH) ≥3 × upper limit of normal, based on 2 measurements from separate blood samples
collected at least 1 day apart during screening
4. Willing and able to give written informed consent and comply with the study visit schedule
5. Documented meningococcal vaccination not more than 3 years prior to dosing
6. Female patients who consider themselves postmenopausal must provide evidence at screening of menopause status,
based on a combination of amenorrhea for at least 1 year and increased serum follicle-stimulating hormone level
(> 30 IU/L) on at least 2 occasions (eg, in the absence of hormone replacement therapy, dietary phytoestrogens) or
estradiol concentration < 10 pg/mL.
7. Female patients of childbearing potential must use highly effective contraception as defined below, starting at screening
and continuing until at least 6 months after the last dose of ALXN1210. Highly effective contraceptive methods are as
follows:
a. Combined (estrogen and progestogen) hormonal contraception associated with inhibition of ovulation:
i. Oral
ii. Intravaginal
iii. Transdermal
b. Progesterone-only hormonal contraception associated with inhibition of ovulation
i. Oral
ii. Injectable
iii. Implantable
c. Intrauterine device
d. Intrauterine hormone-releasing system
e. Bilateral tubal occlusion
8. Male patients with a female spouse/partner of childbearing potential or a pregnant or breastfeeding spouse or partner
must agree to use barrier contraception (male condom) during the Treatment Period and for at least 6 months after the
last dose of ALXN1210. Barrier contraception is required even with documented medical assessment of surgical success
of a vasectomy. Female spouses/partners of male patients who are of childbearing potential must use highly effective
contraception (as defined in inclusion criterion #7) or acceptable contraception, as defined below, starting at screening
and continuing until at least 6 months after the last dose of ALXN1210. Male patients must not donate sperm during the
Screening and Treatment Periods and for at least 6 months after the last dose of ALXN1210.
a. Acceptable contraceptive methods are as follows:
i. Simultaneous use of male condom and appropriate barrier methods for the female partner
Exclusion Criteria
Exclusion Criteria:
1. Treatment with a complement inhibitor at any time
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. History of Neisseria meningitidis infection; history of unexplained, recurrent infection; or infection requiring treatment
with systemic antibiotics within the last 90 days prior to dosing on Day 1
6. Female patients who are planning to become pregnant, or are pregnant or breastfeeding
7. Positive pregnancy test at screening or Day 1
8. Patients are excluded if they are taking:
a. Erythropoietin or immunosuppressants and are not on a stable dose for at least 26 weeks prior to screening
b. Corticosteroids and are not on a stable dose for at least 4 weeks prior to screening
c. Vitamin K antagonists (Coumadin, warfarin), but did not have a stable international normalized ratio level for
4 weeks prior to screening.
d. Iron supplements or folic acid, but have not been on a stable dose for 4 weeks prior to screening
e. Low molecular weight heparin, but have not been on a stable dose for 4 weeks prior to screening
9. Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody titer)
10. Acute or chronic hepatitis B virus infection (evidenced by the presence of hepatitis B surface antigen or
immunoglobulin M antibodies against hepatitis B core antigen)
11. Acute or chronic hepatitis C virus infection (evidenced by antibody titer)
12. Active systemic bacterial, viral, or fungal infection within 14 days prior to dosing on Day 1
13. Immunization with a live-attenuated vaccine 1 month prior to dosing on Day 1
14. Participation in a clinical study within 30 days before initiation of dosing on Day 1, or use of any experimental therapy
within 30 days prior to dosing on Day 1, or within 5 half-lives of the investigational product, whichever is greater
15. Major surgery within 90 days prior to dosing on Day 1
16. Presence of fever (body temperature > 37.6°C (99.7° F) [eg, associated with a symptomatic viral or bacterial infection]
within 2 weeks prior to the first dosing on Day 1
17. Patients with a 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.
18. Known history of severe allergic or anaphylactic reactions to any drug (including vaccines) or allergen
19. History of allergy to excipients of ALXN1210 (ie, polysorbate 80)
20. Known allergy to Chinese hamster ovary cell proteins
21. History of any clinically significant cardiac, hepatic, immunologic, pulmonary, or rheumatoid disease that, in the
Investigator’s judgment, would preclude participation
22. Inability to comply with study requirements
23. Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the patient unsuitable for enrollment
1. Treatment with a complement inhibitor at any time
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. History of Neisseria meningitidis infection; history of unexplained, recurrent infection; or infection requiring treatment
with systemic antibiotics within the last 90 days prior to dosing on Day 1
6. Female patients who are planning to become pregnant, or are pregnant or breastfeeding
7. Positive pregnancy test at screening or Day 1
8. Patients are excluded if they are taking:
a. Erythropoietin or immunosuppressants and are not on a stable dose for at least 26 weeks prior to screening
b. Corticosteroids and are not on a stable dose for at least 4 weeks prior to screening
c. Vitamin K antagonists (Coumadin, warfarin), but did not have a stable international normalized ratio level for
4 weeks prior to screening.
d. Iron supplements or folic acid, but have not been on a stable dose for 4 weeks prior to screening
e. Low molecular weight heparin, but have not been on a stable dose for 4 weeks prior to screening
9. Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody titer)
10. Acute or chronic hepatitis B virus infection (evidenced by the presence of hepatitis B surface antigen or
immunoglobulin M antibodies against hepatitis B core antigen)
11. Acute or chronic hepatitis C virus infection (evidenced by antibody titer)
12. Active systemic bacterial, viral, or fungal infection within 14 days prior to dosing on Day 1
13. Immunization with a live-attenuated vaccine 1 month prior to dosing on Day 1
14. Participation in a clinical study within 30 days before initiation of dosing on Day 1, or use of any experimental therapy
within 30 days prior to dosing on Day 1, or within 5 half-lives of the investigational product, whichever is greater
15. Major surgery within 90 days prior to dosing on Day 1
16. Presence of fever (body temperature > 37.6°C (99.7° F) [eg, associated with a symptomatic viral or bacterial infection]
within 2 weeks prior to the first dosing on Day 1
17. Patients with a 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.
18. Known history of severe allergic or anaphylactic reactions to any drug (including vaccines) or allergen
19. History of allergy to excipients of ALXN1210 (ie, polysorbate 80)
20. Known allergy to Chinese hamster ovary cell proteins
21. History of any clinically significant cardiac, hepatic, immunologic, pulmonary, or rheumatoid disease that, in the
Investigator’s judgment, would preclude participation
22. Inability to comply with study requirements
23. Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the patient unsuitable for enrollment
The Estimated Number of Participants
-
Taiwan
4 participants
-
Global
18 participants
