Clinical Trials List
Protocol NumberALXN1210-aHUS-311
2017-07-01 - 2020-02-16
Phase III
Terminated4
ICD-10D59.3
Hemolytic-uremic syndrome
ICD-9283.11
Non-autoimmune hemolytic anemias, Hemolytic-uremic syndrome
Single Arm Study of ALXN1210 in Complement Inhibitor Treatment-Naïve Adult and Adolescent Patients with Atypical Hemolytic Uremic Syndrome (aHUS)
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Trial Applicant
IQVIA RDS Taiwan Ltd.
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Sponsor
-
Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 林建志 Division of Pediatrics
- Ya-Chung Tian Division of Nephrology
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 陳怡儒 Division of Nephrology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Atypical Hemolytic Uremic Syndrome (aHUS)
Objectives
The primary objective of the study is to assess the efficacy of ALXN1210 in complement inhibitor treatment-naïve adolescent and adult patients with aHUS to inhibit complement-mediated thrombotic microangiopathy (TMA) as characterized by thrombocytopenia, hemolysis, and renal impairment.
Test Drug
ALXN1210
Active Ingredient
Dosage Form
Dosage
10mg/mL
Endpoints
Primary Objective:
The primary objective of the study is to assess the efficacy of ALXN1210 in complement inhibitor treatment-naïve adolescent and adult patients with aHUS to inhibit complement-mediated thrombotic microangiopathy (TMA) as characterized by thrombocytopenia, hemolysis, and renal impairment.
Secondary Objectives:
The secondary objectives of the study are to assess the following:
1. To characterize the safety and tolerability of ALXN1210 in this patient population
2. To evaluate the efficacy of ALXN1210 by the following additional measures:
a. Dialysis requirement status
b. Time to Complete TMA Response
c. Complete TMA Response status over time
d. Observed value and change from baseline in estimated glomerular filtration rate (eGFR)
e. Chronic kidney disease (CKD) stage, as evaluated by eGFR at select target days and classified as improved, stable (no change), or worsened compared to baseline
f. Observed value and change from baseline in hematologic parameters (platelets, lactate
dehydrogenase [LDH], hemoglobin)
g. Increase in hemoglobin of ≥ 20 g/L from baseline, observed at 2 separate assessments obtained at least 4 weeks (28 days) apart, and any measurement in between
h. Change from baseline in quality of life (QoL), as measured by EuroQol 5 dimensions 3 level (EQ5D-3L; all patients), Functional Assessment of Chronic Therapy (FACIT) Fatigue version 4 (patients ≥ 18 years of age), and Pediatric FACIT Fatigue (patients < 18 years of age) questionnaires
3. To characterize the pharmacokinetics (PK)/pharmacodynamics (PD) of ALXN1210 by the following measures:
a. Changes in serum ALXN1210 concentration over time
b. Changes in free complement component 5 (C5) concentrations over time
4. To evaluate the long-term safety and efficacy of ALXN1210
The primary objective of the study is to assess the efficacy of ALXN1210 in complement inhibitor treatment-naïve adolescent and adult patients with aHUS to inhibit complement-mediated thrombotic microangiopathy (TMA) as characterized by thrombocytopenia, hemolysis, and renal impairment.
Secondary Objectives:
The secondary objectives of the study are to assess the following:
1. To characterize the safety and tolerability of ALXN1210 in this patient population
2. To evaluate the efficacy of ALXN1210 by the following additional measures:
a. Dialysis requirement status
b. Time to Complete TMA Response
c. Complete TMA Response status over time
d. Observed value and change from baseline in estimated glomerular filtration rate (eGFR)
e. Chronic kidney disease (CKD) stage, as evaluated by eGFR at select target days and classified as improved, stable (no change), or worsened compared to baseline
f. Observed value and change from baseline in hematologic parameters (platelets, lactate
dehydrogenase [LDH], hemoglobin)
g. Increase in hemoglobin of ≥ 20 g/L from baseline, observed at 2 separate assessments obtained at least 4 weeks (28 days) apart, and any measurement in between
h. Change from baseline in quality of life (QoL), as measured by EuroQol 5 dimensions 3 level (EQ5D-3L; all patients), Functional Assessment of Chronic Therapy (FACIT) Fatigue version 4 (patients ≥ 18 years of age), and Pediatric FACIT Fatigue (patients < 18 years of age) questionnaires
3. To characterize the pharmacokinetics (PK)/pharmacodynamics (PD) of ALXN1210 by the following measures:
a. Changes in serum ALXN1210 concentration over time
b. Changes in free complement component 5 (C5) concentrations over time
4. To evaluate the long-term safety and efficacy of ALXN1210
Inclution Criteria
Inclusion Criteria:
1. Male or female patients ≥ 12 years of age and weighing ≥ 40 kg at the time of consent.
2. Evidence of TMA, including thrombocytopenia, evidence of hemolysis, and kidney injury, based on the following Screening Visit laboratory findings:
a. Platelet count < 150,000 per microliter (µL), and
b. LDH ≥ 1.5 × upper limit of normal (ULN), and hemoglobin ≤ lower limit of normal (LLN) for age and gender, and
c. Serum creatinine level ≥ ULN in adults (≥18 years of age), or ≥ 97.5th percentile for age at Screening in adolescents (≥ 12 to < 18 years of age) (patients who require dialysis for acute kidney injury are also eligible).
3. Among patients with a kidney transplant:
a. Known history of aHUS prior to current kidney transplant, or
b. No known history of aHUS, and persistent evidence of TMA at least 4 days after modifying the immunosuppressive regimen (eg, suspending or reducing the dose) of calcineurin inhibitor ([CNI]; eg, cyclosporine, tacrolimus) or mammalian target of rapamycin inhibitor ([mTORi]; eg, sirolimus, everolimus).
4. Among patients with onset of TMA postpartum, persistent evidence of TMA for > 3 days after the day of childbirth.
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 receive a meningococcal vaccine less than 2 weeks before initiating ALXN1210 treatment must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Patients who have not been vaccinated prior to initiating ALXN1210 treatment should receive prophylactic antibiotics
prior to and for at least 2 weeks after meningococcal vaccination.
6. Patients < 18 years of age must have been vaccinated against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae according to national and local vaccination schedule guidelines.
7. 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.
8. Willing and able to give written informed consent and comply with the study visit schedule. For patients < 18 years of age, patient's legal guardian must be willing and able to give written informed consent and the patient must be willing to give written informed assent (if applicable as determined by the central or local Institutional Review Board [IRB]/Institutional (or Independent) Ethics Committee [IEC]).
1. Male or female patients ≥ 12 years of age and weighing ≥ 40 kg at the time of consent.
2. Evidence of TMA, including thrombocytopenia, evidence of hemolysis, and kidney injury, based on the following Screening Visit laboratory findings:
a. Platelet count < 150,000 per microliter (µL), and
b. LDH ≥ 1.5 × upper limit of normal (ULN), and hemoglobin ≤ lower limit of normal (LLN) for age and gender, and
c. Serum creatinine level ≥ ULN in adults (≥18 years of age), or ≥ 97.5th percentile for age at Screening in adolescents (≥ 12 to < 18 years of age) (patients who require dialysis for acute kidney injury are also eligible).
3. Among patients with a kidney transplant:
a. Known history of aHUS prior to current kidney transplant, or
b. No known history of aHUS, and persistent evidence of TMA at least 4 days after modifying the immunosuppressive regimen (eg, suspending or reducing the dose) of calcineurin inhibitor ([CNI]; eg, cyclosporine, tacrolimus) or mammalian target of rapamycin inhibitor ([mTORi]; eg, sirolimus, everolimus).
4. Among patients with onset of TMA postpartum, persistent evidence of TMA for > 3 days after the day of childbirth.
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 receive a meningococcal vaccine less than 2 weeks before initiating ALXN1210 treatment must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Patients who have not been vaccinated prior to initiating ALXN1210 treatment should receive prophylactic antibiotics
prior to and for at least 2 weeks after meningococcal vaccination.
6. Patients < 18 years of age must have been vaccinated against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae according to national and local vaccination schedule guidelines.
7. 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.
8. Willing and able to give written informed consent and comply with the study visit schedule. For patients < 18 years of age, patient's legal guardian must be willing and able to give written informed consent and the patient must be willing to give written informed assent (if applicable as determined by the central or local Institutional Review Board [IRB]/Institutional (or Independent) Ethics Committee [IEC]).
Exclusion Criteria
Exclusion Criteria:
1. Known familial or acquired ‘a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13’ (ADAMTS13) deficiency (activity < 5%).
2. Known Shiga toxin-related hemolytic uremic syndrome (ST-HUS) as demonstrated by a positive test for Shiga toxin or culture of Shiga toxin producing bacteria.
3. Positive direct Coombs test.
4. Known Human Immunodeficiency Virus (HIV) infection.
5. Unresolved meningococcal disease.
6. Patients with a confirmed diagnosis of ongoing sepsis defined as positive blood cultures within 7 days prior to the start of Screening and untreated with antibiotics.
7. Presence or suspicion of active and untreated systemic bacterial infection that, in the opinion of the Investigator, confounds an accurate diagnosis of aHUS or impedes the ability to manage the aHUS disease.
8. Pregnancy or breastfeeding.
9. Heart, lung, small bowel, pancreas, or liver transplant.
10. Among patients with a kidney transplant, acute kidney dysfunction within 4 weeks of transplant consistent with the diagnosis of acute antibody-mediated rejection (AMR) according to Banff 2013 criteria.
11. Among patients without a kidney transplant, history of kidney disease other than aHUS, such as:
a. Known kidney biopsy finding suggestive of underlying disease other than aHUS
b. Known kidney ultrasound finding consistent with an alternative diagnosis to aHUS (eg small kidneys for age)
c. Known family history and/or genetic diagnosis of noncomplement mediated genetic renal disease (eg, focal segmental glomerulosclerosis)
12. Identified drug exposure-related HUS.
13. Receiving plasma exchange/plasma infusion (PE/PI), for 28 days or longer, prior to the start of Screening for the current TMA.
14. 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.
15. Bone marrow transplant (BMT)/hematopoietic stem cell transplant (HSCT) within the last 6 months prior to the start of Screening.
16. HUS related to vitamin B12 deficiency.
17. Known systemic sclerosis (scleroderma), systemic lupus erythematosus (SLE), or antiphospholipid antibody positivity or syndrome.
18. Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy for end-stage kidney disease [ESKD]).
19. Patients receiving chronic intravenous immunoglobulin (IVIg) within 8 weeks prior to the start of Screening, unless for unrelated medical condition (eg, hypogammaglobinemia); or chronic rituximab therapy within 12 weeks prior to the start of Screening.
20. Patients receiving other immunosuppressive therapies such as steroids, mTORi (eg, sirolimus, everolimus), CNI (eg, cyclosporine or tacrolimus) are excluded unless:
a. part of an established post-transplant antirejection regimen, or
b. patient has confirmed anti-complement factor antibodies requiring immunosuppressive therapy, or
c. steroids are being used for a condition other than aHUS (eg, asthma).
21. 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.
22. Prior use of eculizumab or other complement inhibitors
23. Hypersensitivity to any ingredient contained in the study drug, including hypersensitivity to murine proteins.
24. Any medical or psychological condition that, in the opinion of the Investigator, could increase the risk to the patient by participating in the study or confound the outcome of the study.
25. Known or suspected history of drug or alcohol abuse or dependence within 1 year prior to the start of Screening.
26. Use of tranexamic acid within 7 days prior to Screening is prohibited.
1. Known familial or acquired ‘a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13’ (ADAMTS13) deficiency (activity < 5%).
2. Known Shiga toxin-related hemolytic uremic syndrome (ST-HUS) as demonstrated by a positive test for Shiga toxin or culture of Shiga toxin producing bacteria.
3. Positive direct Coombs test.
4. Known Human Immunodeficiency Virus (HIV) infection.
5. Unresolved meningococcal disease.
6. Patients with a confirmed diagnosis of ongoing sepsis defined as positive blood cultures within 7 days prior to the start of Screening and untreated with antibiotics.
7. Presence or suspicion of active and untreated systemic bacterial infection that, in the opinion of the Investigator, confounds an accurate diagnosis of aHUS or impedes the ability to manage the aHUS disease.
8. Pregnancy or breastfeeding.
9. Heart, lung, small bowel, pancreas, or liver transplant.
10. Among patients with a kidney transplant, acute kidney dysfunction within 4 weeks of transplant consistent with the diagnosis of acute antibody-mediated rejection (AMR) according to Banff 2013 criteria.
11. Among patients without a kidney transplant, history of kidney disease other than aHUS, such as:
a. Known kidney biopsy finding suggestive of underlying disease other than aHUS
b. Known kidney ultrasound finding consistent with an alternative diagnosis to aHUS (eg small kidneys for age)
c. Known family history and/or genetic diagnosis of noncomplement mediated genetic renal disease (eg, focal segmental glomerulosclerosis)
12. Identified drug exposure-related HUS.
13. Receiving plasma exchange/plasma infusion (PE/PI), for 28 days or longer, prior to the start of Screening for the current TMA.
14. 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.
15. Bone marrow transplant (BMT)/hematopoietic stem cell transplant (HSCT) within the last 6 months prior to the start of Screening.
16. HUS related to vitamin B12 deficiency.
17. Known systemic sclerosis (scleroderma), systemic lupus erythematosus (SLE), or antiphospholipid antibody positivity or syndrome.
18. Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy for end-stage kidney disease [ESKD]).
19. Patients receiving chronic intravenous immunoglobulin (IVIg) within 8 weeks prior to the start of Screening, unless for unrelated medical condition (eg, hypogammaglobinemia); or chronic rituximab therapy within 12 weeks prior to the start of Screening.
20. Patients receiving other immunosuppressive therapies such as steroids, mTORi (eg, sirolimus, everolimus), CNI (eg, cyclosporine or tacrolimus) are excluded unless:
a. part of an established post-transplant antirejection regimen, or
b. patient has confirmed anti-complement factor antibodies requiring immunosuppressive therapy, or
c. steroids are being used for a condition other than aHUS (eg, asthma).
21. 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.
22. Prior use of eculizumab or other complement inhibitors
23. Hypersensitivity to any ingredient contained in the study drug, including hypersensitivity to murine proteins.
24. Any medical or psychological condition that, in the opinion of the Investigator, could increase the risk to the patient by participating in the study or confound the outcome of the study.
25. Known or suspected history of drug or alcohol abuse or dependence within 1 year prior to the start of Screening.
26. Use of tranexamic acid within 7 days prior to Screening is prohibited.
The Estimated Number of Participants
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Taiwan
5 participants
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Global
55 participants
