Clinical Trials List
Protocol NumberALXN1920-PMN-201
NCT Number(ClinicalTrials.gov Identfier)NCT07157787
Active
2025-08-01 - 2028-12-31
Phase II
Recruiting3
ICD-10E10.21
Type 1 diabetes mellitus with diabetic nephropathy
ICD-10E11.21
Type 2 diabetes mellitus with diabetic nephropathy
ICD-10N16
Renal tubulo-interstitial disorders in diseases classified elsewhere
ICD-9583.81
Nephritis and nephropathy, not specified as acute or chronic, in diseases classified elsewhere
A Phase 2a, Randomized, Double-blind, Placebo-controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of ALXN1920 in Adult Participants with PMN (Primary Membranous Nephropathy) who are at a High Risk for Disease Progression
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Sponsor
Alexion Pharmaceuticals, Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2026/10/14
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- TUNG-MIN YU Division of Nephrology
- Ming-Ju Wu Division of Nephrology
- 黃俊德 Division of Nephrology
- 蔡尚峰 Division of Nephrology
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Kun-Hua Tu
Co-Principal Investigator
- Guan-Hsing Chen Division of Nephrology
- 何文佑 Division of Nephrology
- 塗貽然 Division of Nephrology
- 鄭雅蓮 Division of Nephrology
- 陳佳晉 Division of Nephrology
- 呂悅安 Division of Nephrology
- Ya-Chung Tian
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Primary Membranous Nephropathy
Objectives
ALXN1920 is a novel fusion protein currently being evaluated in a Phase 2a trial to provide intrarenal complement alternative pathway (CAP) modulation in adult subjects with PMN. The objective of this trial is to evaluate the efficacy, safety, PK, PD and immunogenicity of ALXN1920 in adult subjects with PMN who are at high risk of disease progression. The trial will enroll approximately 30 subjects receiving standard of care (SoC) and evaluate weekly subcutaneous (SC) infusions of 450 mg ALXN1920 compared with placebo over 26 weeks, focusing on changes in proteinuria based on the 24-hour urine total protein to creatinine ratio (UPCR) as the primary endpoint.
Test Drug
ALXN1920
Active Ingredient
ALXN1920
Dosage Form
subcutaneous injection
Dosage
50 mg/mL
Endpoints
Change From Baseline in Proteinuria Based on 24-hour UPCR at Week 26
Inclution Criteria
Age
1. Subjects must be ≥ 18 years and ≤ 75 years old at the time of signing the subject consent form.
Subject Type and Disease Characteristics
2. Subjects diagnosed with primary membranous nephropathy based on a positive antiphospholipase A2 receptor antibody concentration (> 50 RU/mL) at screening, confirmed by a central laboratory.
3. Subjects at high risk of disease exacerbation are defined as:
a. Subjects who have received angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists for at least 8 weeks prior to screening, with the dose adjusted to the maximum tolerated level; however, if a subject has used angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists for less than 8 weeks prior to screening, or has not yet reached the maximum tolerated dose, they will enter a maximum 8-week induction period (see Sections 5.8 and 6.9.1.1.1);
b. Subjects who have received angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists for at least 8 weeks, and whose systolic blood pressure readings have been <140 mmHg for ≥75% of the past 8 weeks, are eligible for randomization;
c. Subjects who have undergone two proteinuria measurements using 24-hour urine collection or a single urine sample, with each measurement showing >3.5 g/day, and the second measurement showing a decrease of ≤50% compared to the first measurement (see Section 5.6).
Sex and Contraception/Barrier Requirements
4. Male or female as designated at birth, including all sex identities.
5. Consent to follow the contraceptive guidelines outlined in the trial protocol, as described in Section 10.5.
Contraceptive methods must comply with local regulations regarding contraceptive methods for clinical trial participants.
a. Male Participants: Eligible participants are those who agree to follow the following guidelines during the trial treatment and for at least 3 months after the last dose of trial treatment:
• Avoid donating sperm; in addition, one of the following conditions must be met:
• Abstain from sexual activity that could result in pregnancy (i.e., prolonged abstinence) and agree to continue abstinence; or
• Must consent to the use of contraceptive methods, detailed below:
Consent to use external condoms during sexual intercourse with a fertile partner, and simultaneously adopt another highly effective contraceptive method with an annual failure rate of less than 1%, as described in Section 10.5, "Contraception/Barrier Requirements."
Consent to use external condoms in any activity where semen may be transferred to others.
b. Female Participants: Participants are eligible to participate if they are not pregnant or breastfeeding and meet one of the following criteria:
• Are infertile women, as defined in Section 10.5, Contraception and Barrier Methods.
• Are fertile and have used a highly effective (annual failure rate < 1%) method of contraception (a low-user-dependency method, as described in Section 10.5, Contraception and Barrier Methods) during the trial treatment and for at least 6 months after the last dose of trial treatment, and have agreed not to donate oocytes (eggs, oocytes) for reproductive purposes during this period. The trial administrator should assess the possibility that the contraceptive method has not yet become effective at the time of the first dose of trial treatment (e.g., non-compliance, recent initiation).
• Fertility-prone participants must undergo a high-sensitivity pregnancy test (serum test at screening and urine test on day 1 of trial treatment) prior to the first dose of trial treatment, in accordance with local regulations, and the result must be negative (see Section 8.3.6, Pregnancy Testing).
• If a urine test is not confirming a negative result (e.g., inconclusive), a serum pregnancy test must be performed. In this case, if the subject's serum pregnancy test result is positive, they should not be admitted.
• For additional pregnancy testing requirements during and after the trial treatment, please refer to Section 8.3.6, Pregnancy Testing.
• The trial administrator is responsible for reviewing medical history, menstrual history, and recent sexual activity to avoid admitting subjects who are unaware they are in early pregnancy.
Informed Consent
6. A signed subject consent form (as described in Section 10.1.3) that includes compliance with the subject consent form and the requirements and limitations listed in this trial protocol.
Previous/Concomitant Therapies
7. The subject agrees to receive standard care, as described in Section 6.9.1.1.
Prophylactic Antibiotic Requirements
8. To reduce the risk of infection, all subjects must receive appropriate prophylactic antibiotic treatment during Rituximab treatment and agree to receive a meningococcal vaccine; see Section 8.3.10 for details.
1. Subjects must be ≥ 18 years and ≤ 75 years old at the time of signing the subject consent form.
Subject Type and Disease Characteristics
2. Subjects diagnosed with primary membranous nephropathy based on a positive antiphospholipase A2 receptor antibody concentration (> 50 RU/mL) at screening, confirmed by a central laboratory.
3. Subjects at high risk of disease exacerbation are defined as:
a. Subjects who have received angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists for at least 8 weeks prior to screening, with the dose adjusted to the maximum tolerated level; however, if a subject has used angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists for less than 8 weeks prior to screening, or has not yet reached the maximum tolerated dose, they will enter a maximum 8-week induction period (see Sections 5.8 and 6.9.1.1.1);
b. Subjects who have received angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists for at least 8 weeks, and whose systolic blood pressure readings have been <140 mmHg for ≥75% of the past 8 weeks, are eligible for randomization;
c. Subjects who have undergone two proteinuria measurements using 24-hour urine collection or a single urine sample, with each measurement showing >3.5 g/day, and the second measurement showing a decrease of ≤50% compared to the first measurement (see Section 5.6).
Sex and Contraception/Barrier Requirements
4. Male or female as designated at birth, including all sex identities.
5. Consent to follow the contraceptive guidelines outlined in the trial protocol, as described in Section 10.5.
Contraceptive methods must comply with local regulations regarding contraceptive methods for clinical trial participants.
a. Male Participants: Eligible participants are those who agree to follow the following guidelines during the trial treatment and for at least 3 months after the last dose of trial treatment:
• Avoid donating sperm; in addition, one of the following conditions must be met:
• Abstain from sexual activity that could result in pregnancy (i.e., prolonged abstinence) and agree to continue abstinence; or
• Must consent to the use of contraceptive methods, detailed below:
Consent to use external condoms during sexual intercourse with a fertile partner, and simultaneously adopt another highly effective contraceptive method with an annual failure rate of less than 1%, as described in Section 10.5, "Contraception/Barrier Requirements."
Consent to use external condoms in any activity where semen may be transferred to others.
b. Female Participants: Participants are eligible to participate if they are not pregnant or breastfeeding and meet one of the following criteria:
• Are infertile women, as defined in Section 10.5, Contraception and Barrier Methods.
• Are fertile and have used a highly effective (annual failure rate < 1%) method of contraception (a low-user-dependency method, as described in Section 10.5, Contraception and Barrier Methods) during the trial treatment and for at least 6 months after the last dose of trial treatment, and have agreed not to donate oocytes (eggs, oocytes) for reproductive purposes during this period. The trial administrator should assess the possibility that the contraceptive method has not yet become effective at the time of the first dose of trial treatment (e.g., non-compliance, recent initiation).
• Fertility-prone participants must undergo a high-sensitivity pregnancy test (serum test at screening and urine test on day 1 of trial treatment) prior to the first dose of trial treatment, in accordance with local regulations, and the result must be negative (see Section 8.3.6, Pregnancy Testing).
• If a urine test is not confirming a negative result (e.g., inconclusive), a serum pregnancy test must be performed. In this case, if the subject's serum pregnancy test result is positive, they should not be admitted.
• For additional pregnancy testing requirements during and after the trial treatment, please refer to Section 8.3.6, Pregnancy Testing.
• The trial administrator is responsible for reviewing medical history, menstrual history, and recent sexual activity to avoid admitting subjects who are unaware they are in early pregnancy.
Informed Consent
6. A signed subject consent form (as described in Section 10.1.3) that includes compliance with the subject consent form and the requirements and limitations listed in this trial protocol.
Previous/Concomitant Therapies
7. The subject agrees to receive standard care, as described in Section 6.9.1.1.
Prophylactic Antibiotic Requirements
8. To reduce the risk of infection, all subjects must receive appropriate prophylactic antibiotic treatment during Rituximab treatment and agree to receive a meningococcal vaccine; see Section 8.3.10 for details.
Exclusion Criteria
Exclusion Criteria
1. Estimated glomerular filtration rate (GFR) < 60 mL/min/1.73 m² calculated by the Nephrology Epidemiology Collaborative Study Group during the screening period.
2. Documented rapid deterioration of renal function (a decrease in estimated GFR of 20% or more within the 24 months prior to screening, lasting for at least 3 months).
3. History of life-threatening renal syndrome (serum albumin < 2.5 g/dL, and treatment-resistant edema or thromboembolic events) within the year prior to screening.
4. Diagnosis of antiphospholipase A2 receptor-negative membranous nephropathy, or antiphospholipase A2 receptor-positive membranous nephropathy with serum antiphospholipase A2 receptor < 50 RU/mL at screening, or other kidney diseases besides primary membranous nephropathy.
5. History of kidney transplantation, or planned kidney transplantation or dialysis during treatment.
6. History of other solid organ (heart, lung, small intestine, pancreas, or liver) or bone marrow transplantation; or planned transplantation during treatment.
Medical Condition
7. Splenectomy or functional asplenia.
8. Known or suspected complement deficiency, unless caused by an underlying disease.
9. Positive result for Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) at screening.
10. Hepatitis B surface antigen and/or hepatitis B core antibody at screening or within 3 months.
Note: Subjects known to be positive for hepatitis B surface antibody may be randomly assigned provided they have been vaccinated against hepatitis B and are negative for both hepatitis B surface antigen and hepatitis B core antibody.
11. Positive result for hepatitis C antibody at screening or within 3 months, unless data shows a negative result for hepatitis C virus RNA.
12. Subjects with a history of human immunodeficiency virus (HIV) disease who have not received antiretroviral therapy, or who, although treated, had a known detectable viral load within 1 year prior to screening.
13. Subjects with a known medical or psychological condition (including substance abuse) or risk factor that, as determined by the trial administrator, may interfere with the subject's full participation in the trial, pose any additional risk to the subject, or confound the subject's assessment or trial results.
14. Subjects with any history of Neisseria spp. infection.
15. Subjects with a history of unexplained recurrent infections, or who had an infection requiring systemic antibiotic treatment within 90 days prior to Day 1 of the trial treatment.
16. Subjects with an active systemic bacterial, viral, or fungal infection within 14 days prior to the use of the first dose of the investigational drug.
17. Subjects with bundle branch block whose QT interval is >480 msec.
18. Subjects with a history of malignancy within 5 years prior to screening, excluding non-melanoma skin cancer or cervical carcinoma in situ that has been treated and has no evidence of recurrence.
19. History of allergy to any component of the trial treatment, including inability to use or tolerance of permitted concomitant therapies.
20. Body mass index > 40.
21. Poorly controlled hypertension, defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg when using ≥ 3 antihypertensive medications.
22. Abnormal laboratory test results at screening, including:
• Alanine transaminase > 2 times the upper limit of normal
• Direct bilirubin > 2 times the upper limit of normal
• Glycated hemoglobin > 6.5% at screening
23. Any other clinically significant abnormal laboratory test results that, according to the trial administrator, would render the subject unfit to participate in the trial or subject the subject to undue risk.
24. History of type 1 diabetes and a diagnosis of type 2 diabetes.
Previous/Combined Therapies
25. Subjects currently receiving biologic therapy that may affect immune system function, or who have previously received biologic therapy that may affect immune system function, and who discontinued the therapy within 30 days prior to the screening follow-up visit or within 5 biologic drug terminal half-lives (whichever is longer).
26. Subjects who have previously or are currently receiving any complement inhibitor therapy (including but not limited to eculizumab and ravulizumab).
27. Subjects who have used anti-differentiation cluster 20 antibodies within 6 months prior to screening.
28. Subjects currently or previously receiving obinutuzumab.
29. Subjects who have used cyclophosphamide within 6 months prior to screening.
30. Subjects who have used immunosuppressants other than anti-differentiation cluster 20 antibodies or cyclophosphamide within 12 weeks prior to screening.
31. Subjects who cannot use any one antimicrobial drug for the prevention of meningococcal disease.
Previous/Concurrent Clinical Trial Experience
32. Participation in another investigational drug or device study within 30 days prior to the start of the trial treatment on Day 1 of this trial. Or within 5 half-lives of the investigational drug (whichever is longer).
Other Exclusion Criteria
33. Pregnancy, breastfeeding, or intention to conceive during the trial.
34. History of resistance to Rituximab, defined as one of the following:
• A reduction of <25% in proteinuria after 6 months of Rituximab treatment (including any increase in proteinuria), or,
• A reduction of <25% in antiphospholipase A2 receptor antibody concentration after 3 months of Rituximab treatment, or a reduction of <50% in antiphospholipase A2 receptor antibody concentration after 6 months.
Note: Subjects who previously achieved a complete or partial response to Rituximab and relapsed at least 6 months after their last dose of Rituximab are eligible (relapse is defined as a recurrence of proteinuria to >3.5 g/day after achieving a complete or partial response with immunosuppressive therapy).
35. History of intolerance or allergy to angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists, including but not limited to angioedema, persistent cough, or clinically significant hypotension caused by these drugs.
36. Use of sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists, or endothelin receptor antagonists within 8 weeks prior to randomization and throughout the trial.
1. Estimated glomerular filtration rate (GFR) < 60 mL/min/1.73 m² calculated by the Nephrology Epidemiology Collaborative Study Group during the screening period.
2. Documented rapid deterioration of renal function (a decrease in estimated GFR of 20% or more within the 24 months prior to screening, lasting for at least 3 months).
3. History of life-threatening renal syndrome (serum albumin < 2.5 g/dL, and treatment-resistant edema or thromboembolic events) within the year prior to screening.
4. Diagnosis of antiphospholipase A2 receptor-negative membranous nephropathy, or antiphospholipase A2 receptor-positive membranous nephropathy with serum antiphospholipase A2 receptor < 50 RU/mL at screening, or other kidney diseases besides primary membranous nephropathy.
5. History of kidney transplantation, or planned kidney transplantation or dialysis during treatment.
6. History of other solid organ (heart, lung, small intestine, pancreas, or liver) or bone marrow transplantation; or planned transplantation during treatment.
Medical Condition
7. Splenectomy or functional asplenia.
8. Known or suspected complement deficiency, unless caused by an underlying disease.
9. Positive result for Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) at screening.
10. Hepatitis B surface antigen and/or hepatitis B core antibody at screening or within 3 months.
Note: Subjects known to be positive for hepatitis B surface antibody may be randomly assigned provided they have been vaccinated against hepatitis B and are negative for both hepatitis B surface antigen and hepatitis B core antibody.
11. Positive result for hepatitis C antibody at screening or within 3 months, unless data shows a negative result for hepatitis C virus RNA.
12. Subjects with a history of human immunodeficiency virus (HIV) disease who have not received antiretroviral therapy, or who, although treated, had a known detectable viral load within 1 year prior to screening.
13. Subjects with a known medical or psychological condition (including substance abuse) or risk factor that, as determined by the trial administrator, may interfere with the subject's full participation in the trial, pose any additional risk to the subject, or confound the subject's assessment or trial results.
14. Subjects with any history of Neisseria spp. infection.
15. Subjects with a history of unexplained recurrent infections, or who had an infection requiring systemic antibiotic treatment within 90 days prior to Day 1 of the trial treatment.
16. Subjects with an active systemic bacterial, viral, or fungal infection within 14 days prior to the use of the first dose of the investigational drug.
17. Subjects with bundle branch block whose QT interval is >480 msec.
18. Subjects with a history of malignancy within 5 years prior to screening, excluding non-melanoma skin cancer or cervical carcinoma in situ that has been treated and has no evidence of recurrence.
19. History of allergy to any component of the trial treatment, including inability to use or tolerance of permitted concomitant therapies.
20. Body mass index > 40.
21. Poorly controlled hypertension, defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg when using ≥ 3 antihypertensive medications.
22. Abnormal laboratory test results at screening, including:
• Alanine transaminase > 2 times the upper limit of normal
• Direct bilirubin > 2 times the upper limit of normal
• Glycated hemoglobin > 6.5% at screening
23. Any other clinically significant abnormal laboratory test results that, according to the trial administrator, would render the subject unfit to participate in the trial or subject the subject to undue risk.
24. History of type 1 diabetes and a diagnosis of type 2 diabetes.
Previous/Combined Therapies
25. Subjects currently receiving biologic therapy that may affect immune system function, or who have previously received biologic therapy that may affect immune system function, and who discontinued the therapy within 30 days prior to the screening follow-up visit or within 5 biologic drug terminal half-lives (whichever is longer).
26. Subjects who have previously or are currently receiving any complement inhibitor therapy (including but not limited to eculizumab and ravulizumab).
27. Subjects who have used anti-differentiation cluster 20 antibodies within 6 months prior to screening.
28. Subjects currently or previously receiving obinutuzumab.
29. Subjects who have used cyclophosphamide within 6 months prior to screening.
30. Subjects who have used immunosuppressants other than anti-differentiation cluster 20 antibodies or cyclophosphamide within 12 weeks prior to screening.
31. Subjects who cannot use any one antimicrobial drug for the prevention of meningococcal disease.
Previous/Concurrent Clinical Trial Experience
32. Participation in another investigational drug or device study within 30 days prior to the start of the trial treatment on Day 1 of this trial. Or within 5 half-lives of the investigational drug (whichever is longer).
Other Exclusion Criteria
33. Pregnancy, breastfeeding, or intention to conceive during the trial.
34. History of resistance to Rituximab, defined as one of the following:
• A reduction of <25% in proteinuria after 6 months of Rituximab treatment (including any increase in proteinuria), or,
• A reduction of <25% in antiphospholipase A2 receptor antibody concentration after 3 months of Rituximab treatment, or a reduction of <50% in antiphospholipase A2 receptor antibody concentration after 6 months.
Note: Subjects who previously achieved a complete or partial response to Rituximab and relapsed at least 6 months after their last dose of Rituximab are eligible (relapse is defined as a recurrence of proteinuria to >3.5 g/day after achieving a complete or partial response with immunosuppressive therapy).
35. History of intolerance or allergy to angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists, including but not limited to angioedema, persistent cough, or clinically significant hypotension caused by these drugs.
36. Use of sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists, or endothelin receptor antagonists within 8 weeks prior to randomization and throughout the trial.
The Estimated Number of Participants
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Taiwan
9 participants
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Global
30 participants
