Clinical Trials List
Protocol NumberALXN2220-ATTR-CM-301
2023-12-15 - 2028-06-30
Phase III
Recruiting5
ICD-10E85.0
Non-neuropathic heredofamilial amyloidosis
ICD-10E85.1
Neuropathic heredofamilial amyloidosis
ICD-10E85.2
Heredofamilial amyloidosis, unspecified
ICD-10E85.3
Secondary systemic amyloidosis
ICD-10E85.4
Organ-limited amyloidosis
ICD-10E85.8
Other amyloidosis
ICD-10E85.9
Amyloidosis, unspecified
ICD-9277.3
Amyloidosis
A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Amyloid Depleter ALXN2220 in Adult Participants with Transthyretin Amyloid Cardiomyopathy (ATTR-CM)
-
Sponsor
ALEXION PHARMA TAIWAN LTD
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/11/06
Investigators and Locations
Co-Principal Investigator
- Shih-Hsien Sung 無
- 黃偉銘 無
- Yi-Chun Lee 無
- 廖若男 無
- 季康揚 無
- Kon-Ping Lin 無
- Yi-Chu Liao 無
- 王維庭 無
- 郭泠 無
- Yo-Tsen Liu 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 董承昌 無
- 林晏年 無
- Yuh-Cherng Guo 無
- 呂尚謁 無
- 鍾偉信 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 許榮城 無
- 曾炳憲 無
- 林恆旭 無
- YEN-HSIANG HUANG 無
- 莊文博 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
CHIH-HUNG LAI
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Transthyretin amyloid cardiomyopathy
Objectives
The aim of this trial was to evaluate the efficacy and safety of ALXN2220 in adult participants with ATTR-CM treated with standard therapy.
Test Drug
ALXN2220
Active Ingredient
ALXN2220
Dosage Form
Liquid in Single dose vial
Dosage
50 mg/mL
Endpoints
The efficacy of ALXN2220 in adult participants with ATTR-CM was evaluated based on the composite endpoint of all-cause mortality (ACM) and total CV clinical events, compared with the placebo group.
Inclution Criteria
Age
1. Males or females aged ≥18 years and ≥90 years at randomization.
Participant Categories and Disease Characteristics
2. Confirmation of cardiac amyloidosis by diagnosis of ATTR-CM with wild-type or variant TTR genotypes according to one of the following methods:
a. Confirmation of TTR amyloid protein typing by immunohistochemistry or mass spectrometry in endocardial myocardial sections
or
b. Grade 2 or 3 cardiac contrast enhancement by 99mTc scintillation angiography (99mTc DPD, 99mTc PYP, or 99mTc HMDP) in the absence of monoglobulinemia
or
c. Grade 2 or 3 99mTc scintillation angiography (99mTc DPD, 99mTc PYP, or 99mTc HMDP) in the presence of monoglobulinemia
HMDP) and confirmed as TTR amyloid subtype in tissue sections by immunohistochemistry or mass spectrometry.
3. If no previous genetic testing or no genetic testing results are available, willing to undergo genetic testing for mutations in the TTR gene during the screening period.
4. Measure end-diastolic ventricular septal thickness ≤ 12 mm during echocardiography.
5. NT-proBNP (N-terminal pro-B-type diuretic, a heart failure indicator) > 2000 pg/mL at the central laboratory during the screening period.
6. Received cyclic diuretic therapy for at least 30 days prior to screening.
7. A recorded history of heart failure within one year prior to screening, including one of the following events:
a. Hospitalization for heart failure
b. Emergency heart failure presentation
c. Recorded NT-proBNP > 2000 pg/mL (or BNP > 500 pg/mL; e.g., NT-proBNP: BNP = 4:1) Volume overload event
8. Class II to IV of the New York Heart Association (NYHA) at screening
9. Life expectancy of ≤6 months, as determined by the trial physician
10. If already receiving locally approved TTR gene-mediated therapy for transthyretin amyloidosis (ATTR), a stable dose must be maintained for at least 90 days during the screening period.
Sex and Contraception/Impairment Requirements
11. Male and/or female (based on their reproductive organs and function as specified by the entire set of chromosomes)
Note: If fertility changes after the start of the trial (e.g., a female participant who was premenopausal experiences menarche) or pregnancy risk changes (e.g., a female participant who was previously inactive in heterosexual activity becomes active), the participant must discuss this with the trial physician, who should determine whether the female participant must begin using a highly effective method of contraception or the male participant must use condoms. Additional evaluation should be considered if reproductive status is in doubt.
Clinical trial participants should use contraception methods that comply with local contraceptive regulations.
a. Male Participants:
Male participants are eligible to participate in the trial if they agree to the following during the trial intervention and for at least 7 months after the last dose of the trial intervention:
**Avoid donating raw, fresh semen**
And, choose one of the following:
- Abstain from sex as a habitual lifestyle and agree to continue abstinence.
Or
- Must agree to use contraceptive/barrier items, detailed below:
o Agree to use male condoms and should inform the female partner of the benefits of using highly effective contraception, as condoms may break or leak during intercourse with a fertile, non-pregnant woman.
b. Female Participants:
Female participants are eligible to participate in the trial if they are not pregnant or breastfeeding and meet one of the following criteria:
- A woman who is not fertile
Or
- A fertile woman who uses a highly effective contraceptive method during the trial intervention and for at least 5 months after the last dose of the trial intervention and agrees not to donate eggs (ovums, oocytes) for reproductive purposes during this period. During the first dose of the trial intervention, the investigating physician should assess the likelihood of contraceptive failure (e.g., non-compliance, recent use).
Females of childbearing potential must have a negative result on a high-sensitivity pregnancy test (e.g., urine or serum pregnancy test as required by local regulations) at the time of the trial intervention.
- If the urine test is not confirmatory (e.g., indeterminate result), a serum pregnancy test is required. In this case, if the serum pregnancy test result is positive, the participant must be excluded.
- Other requirements for pregnancy testing during and after the trial intervention.
- The investigating physician is responsible for reviewing medical history, menstrual history, and recent sexual activity to minimize the risk of including women with undetected early pregnancies.
Informed Consent
12. Ability to sign the participant consent form, including compliance with the Participant Consent Form (ICF) and the requirements and limitations set forth in this trial plan.
1. Males or females aged ≥18 years and ≥90 years at randomization.
Participant Categories and Disease Characteristics
2. Confirmation of cardiac amyloidosis by diagnosis of ATTR-CM with wild-type or variant TTR genotypes according to one of the following methods:
a. Confirmation of TTR amyloid protein typing by immunohistochemistry or mass spectrometry in endocardial myocardial sections
or
b. Grade 2 or 3 cardiac contrast enhancement by 99mTc scintillation angiography (99mTc DPD, 99mTc PYP, or 99mTc HMDP) in the absence of monoglobulinemia
or
c. Grade 2 or 3 99mTc scintillation angiography (99mTc DPD, 99mTc PYP, or 99mTc HMDP) in the presence of monoglobulinemia
HMDP) and confirmed as TTR amyloid subtype in tissue sections by immunohistochemistry or mass spectrometry.
3. If no previous genetic testing or no genetic testing results are available, willing to undergo genetic testing for mutations in the TTR gene during the screening period.
4. Measure end-diastolic ventricular septal thickness ≤ 12 mm during echocardiography.
5. NT-proBNP (N-terminal pro-B-type diuretic, a heart failure indicator) > 2000 pg/mL at the central laboratory during the screening period.
6. Received cyclic diuretic therapy for at least 30 days prior to screening.
7. A recorded history of heart failure within one year prior to screening, including one of the following events:
a. Hospitalization for heart failure
b. Emergency heart failure presentation
c. Recorded NT-proBNP > 2000 pg/mL (or BNP > 500 pg/mL; e.g., NT-proBNP: BNP = 4:1) Volume overload event
8. Class II to IV of the New York Heart Association (NYHA) at screening
9. Life expectancy of ≤6 months, as determined by the trial physician
10. If already receiving locally approved TTR gene-mediated therapy for transthyretin amyloidosis (ATTR), a stable dose must be maintained for at least 90 days during the screening period.
Sex and Contraception/Impairment Requirements
11. Male and/or female (based on their reproductive organs and function as specified by the entire set of chromosomes)
Note: If fertility changes after the start of the trial (e.g., a female participant who was premenopausal experiences menarche) or pregnancy risk changes (e.g., a female participant who was previously inactive in heterosexual activity becomes active), the participant must discuss this with the trial physician, who should determine whether the female participant must begin using a highly effective method of contraception or the male participant must use condoms. Additional evaluation should be considered if reproductive status is in doubt.
Clinical trial participants should use contraception methods that comply with local contraceptive regulations.
a. Male Participants:
Male participants are eligible to participate in the trial if they agree to the following during the trial intervention and for at least 7 months after the last dose of the trial intervention:
**Avoid donating raw, fresh semen**
And, choose one of the following:
- Abstain from sex as a habitual lifestyle and agree to continue abstinence.
Or
- Must agree to use contraceptive/barrier items, detailed below:
o Agree to use male condoms and should inform the female partner of the benefits of using highly effective contraception, as condoms may break or leak during intercourse with a fertile, non-pregnant woman.
b. Female Participants:
Female participants are eligible to participate in the trial if they are not pregnant or breastfeeding and meet one of the following criteria:
- A woman who is not fertile
Or
- A fertile woman who uses a highly effective contraceptive method during the trial intervention and for at least 5 months after the last dose of the trial intervention and agrees not to donate eggs (ovums, oocytes) for reproductive purposes during this period. During the first dose of the trial intervention, the investigating physician should assess the likelihood of contraceptive failure (e.g., non-compliance, recent use).
Females of childbearing potential must have a negative result on a high-sensitivity pregnancy test (e.g., urine or serum pregnancy test as required by local regulations) at the time of the trial intervention.
- If the urine test is not confirmatory (e.g., indeterminate result), a serum pregnancy test is required. In this case, if the serum pregnancy test result is positive, the participant must be excluded.
- Other requirements for pregnancy testing during and after the trial intervention.
- The investigating physician is responsible for reviewing medical history, menstrual history, and recent sexual activity to minimize the risk of including women with undetected early pregnancies.
Informed Consent
12. Ability to sign the participant consent form, including compliance with the Participant Consent Form (ICF) and the requirements and limitations set forth in this trial plan.
Exclusion Criteria
Exclusion Criteria
Participants will be ineligible for the trial if they meet any of the following criteria:
Medical Conditions
1. Known leptomeningeal amyloidosis
2. Known light chain (AL) or secondary amyloidosis (AA), or any other form of systemic amyloidosis
3. History of multiple myeloma
4. Cardiomyopathy not primarily caused by ATTR-CM, e.g., primarily caused by hypertension, valvular heart disease, or ischemic heart disease (based on the trial administrator's assessment)
5. Acute coronary syndrome, unstable angina, stroke, transient ischemic attack, coronary revascularization, cardiac device implantation, heart valve repair, or major surgery within the three months prior to screening
6. Poorly controlled hypertension (mean normal resting systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg at screening)
7. Mean normal resting systolic blood pressure < 90 mmHg despite appropriate treatment 8. Symptomatic postural hypotension (based on each trial physician's assessment at screening)
9. Poorly controlled clinically significant arrhythmias (based on the trial physician's assessment)
10. Left ventricular ejection fraction (LVEF) < 30%
11. Hemoglobin < 8 g/dL (female) or < 9 g/dL (male), measured by the central laboratory at screening
12. Platelet count < 100,000/mm3 or other lesions associated with clinically significant thrombocytopenia, measured by the central laboratory at screening
13. Alanine transaminase (ALT) > 2.5 × Upper Limit of Normal (ULN), measured by the central laboratory at screening
14. Total bilirubin > 2.5 × ULN (for those with total bilirubin > 2.5 × ULN and known Gilbert's syndrome, only direct bilirubin ≤ 1.5 × ULN is acceptable) ULN (not excluded), measured by the central laboratory during screening.
14. Currently assessed by the trial administrator as having unstable liver or biliary tract disease, defined as pre-existing ascites, encephalopathy, coagulation disorders, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Participants with severe liver impairment (e.g., Child-Pugh C) are ineligible. Participants with hepatitis B (with HBsAg and detectable HBV DNA) or hepatitis C (with HCV antibodies and detectable HCV viral load) are ineligible. Note: Participants meeting the inclusion criteria may be admitted to stable chronic liver disease (including Gilbert's syndrome and asymptomatic gallstones).
15. Having lymphoma, leukemia, or any malignant tumor or clonal stem cell disease (myelodysplastic syndrome, polycythemia vera, essential thrombocythemia, myelofibrosis) within the past 5 years, except for the following:
a. Well-treated basal cell carcinoma or squamous cell carcinoma of the skin, melanoma in situ, or surgically removed cervical carcinoma in situ with no evidence of metastatic disease.
b. Participants with well-treated stage I cancer currently in remission.
c. Well-treated prostate cancer of American Joint Committee on Cancer (AJCC) stage I, IIA, or IIB (Gleason score ≥ 3+4 and prostate-specific antigen < 20 ng/mL).
16. Respiratory insufficiency requiring continuous oxygen therapy during the day.
17. Kidney failure requiring dialysis, or CKD-EPI detected by the central laboratory at the time of screening. Participants with an estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73 m2 as measured by the formula
18. History of solid organ transplantation or ventricular assist device (VAD) or on the waiting list for heart transplantation at the time of screening. Note: A history of planned corneal transplantation is not an exclusion criterion.
19. Secondary polyneuropathy requiring wheelchair use due to ATTR (i.e., polyneuropathy disability (PND) score level 4).
20. Known medical or psychological conditions or risk factors that, according to the investigating physician or commissioning party, may interfere with the participant's full participation in the trial, pose any additional risk to the participant, or obscure the participant's assessment or trial results.
21. Suspected or known intolerance/allergy to any protein or research component.
Weight
22. Weight < 40 kg at screening.
Previous/Concomitant Treatment
23. Previous treatment with an approved or clinically investigated ATTR amyloid consumable (i.e., monoclonal anti-ATTR antibody).
24. Use of drugs not permitted as stated in the protocol.
Previous/Merged Clinical Trial Experience
25. Participation in another clinical trial or taking the investigational drug for 5 half-lives within 30 calendar days prior to signing the informed consent form, whichever is longer. If participating in an open-label extension trial of a Phase III clinical trial using TTR gene-editing as treatment, 30 calendar days after termination of the investigational drug TTR gene-editing is acceptable. If the participant is receiving TTR gene-editing for a locally approved indication, a withdrawal period is not required before screening for this trial.
26. Previous participation in a trial involving CRISPR-Cas9 gene editing for transthyretin amyloidosis.
Diagnostic Assessment
27. History of HIV infection or a positive HIV antibody test by a central laboratory, confirmed by Western ink dot assay or polymerase chain reaction.
Other Exclusion Criteria
28. History of bleeding disorders or coagulation disorders (e.g., antiphospholipid syndrome, congenital diseases such as A...). Hemophilia type I, hemophilia B, and hemophilia-like diseases
Participants will be ineligible for the trial if they meet any of the following criteria:
Medical Conditions
1. Known leptomeningeal amyloidosis
2. Known light chain (AL) or secondary amyloidosis (AA), or any other form of systemic amyloidosis
3. History of multiple myeloma
4. Cardiomyopathy not primarily caused by ATTR-CM, e.g., primarily caused by hypertension, valvular heart disease, or ischemic heart disease (based on the trial administrator's assessment)
5. Acute coronary syndrome, unstable angina, stroke, transient ischemic attack, coronary revascularization, cardiac device implantation, heart valve repair, or major surgery within the three months prior to screening
6. Poorly controlled hypertension (mean normal resting systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg at screening)
7. Mean normal resting systolic blood pressure < 90 mmHg despite appropriate treatment 8. Symptomatic postural hypotension (based on each trial physician's assessment at screening)
9. Poorly controlled clinically significant arrhythmias (based on the trial physician's assessment)
10. Left ventricular ejection fraction (LVEF) < 30%
11. Hemoglobin < 8 g/dL (female) or < 9 g/dL (male), measured by the central laboratory at screening
12. Platelet count < 100,000/mm3 or other lesions associated with clinically significant thrombocytopenia, measured by the central laboratory at screening
13. Alanine transaminase (ALT) > 2.5 × Upper Limit of Normal (ULN), measured by the central laboratory at screening
14. Total bilirubin > 2.5 × ULN (for those with total bilirubin > 2.5 × ULN and known Gilbert's syndrome, only direct bilirubin ≤ 1.5 × ULN is acceptable) ULN (not excluded), measured by the central laboratory during screening.
14. Currently assessed by the trial administrator as having unstable liver or biliary tract disease, defined as pre-existing ascites, encephalopathy, coagulation disorders, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Participants with severe liver impairment (e.g., Child-Pugh C) are ineligible. Participants with hepatitis B (with HBsAg and detectable HBV DNA) or hepatitis C (with HCV antibodies and detectable HCV viral load) are ineligible. Note: Participants meeting the inclusion criteria may be admitted to stable chronic liver disease (including Gilbert's syndrome and asymptomatic gallstones).
15. Having lymphoma, leukemia, or any malignant tumor or clonal stem cell disease (myelodysplastic syndrome, polycythemia vera, essential thrombocythemia, myelofibrosis) within the past 5 years, except for the following:
a. Well-treated basal cell carcinoma or squamous cell carcinoma of the skin, melanoma in situ, or surgically removed cervical carcinoma in situ with no evidence of metastatic disease.
b. Participants with well-treated stage I cancer currently in remission.
c. Well-treated prostate cancer of American Joint Committee on Cancer (AJCC) stage I, IIA, or IIB (Gleason score ≥ 3+4 and prostate-specific antigen < 20 ng/mL).
16. Respiratory insufficiency requiring continuous oxygen therapy during the day.
17. Kidney failure requiring dialysis, or CKD-EPI detected by the central laboratory at the time of screening. Participants with an estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73 m2 as measured by the formula
18. History of solid organ transplantation or ventricular assist device (VAD) or on the waiting list for heart transplantation at the time of screening. Note: A history of planned corneal transplantation is not an exclusion criterion.
19. Secondary polyneuropathy requiring wheelchair use due to ATTR (i.e., polyneuropathy disability (PND) score level 4).
20. Known medical or psychological conditions or risk factors that, according to the investigating physician or commissioning party, may interfere with the participant's full participation in the trial, pose any additional risk to the participant, or obscure the participant's assessment or trial results.
21. Suspected or known intolerance/allergy to any protein or research component.
Weight
22. Weight < 40 kg at screening.
Previous/Concomitant Treatment
23. Previous treatment with an approved or clinically investigated ATTR amyloid consumable (i.e., monoclonal anti-ATTR antibody).
24. Use of drugs not permitted as stated in the protocol.
Previous/Merged Clinical Trial Experience
25. Participation in another clinical trial or taking the investigational drug for 5 half-lives within 30 calendar days prior to signing the informed consent form, whichever is longer. If participating in an open-label extension trial of a Phase III clinical trial using TTR gene-editing as treatment, 30 calendar days after termination of the investigational drug TTR gene-editing is acceptable. If the participant is receiving TTR gene-editing for a locally approved indication, a withdrawal period is not required before screening for this trial.
26. Previous participation in a trial involving CRISPR-Cas9 gene editing for transthyretin amyloidosis.
Diagnostic Assessment
27. History of HIV infection or a positive HIV antibody test by a central laboratory, confirmed by Western ink dot assay or polymerase chain reaction.
Other Exclusion Criteria
28. History of bleeding disorders or coagulation disorders (e.g., antiphospholipid syndrome, congenital diseases such as A...). Hemophilia type I, hemophilia B, and hemophilia-like diseases
The Estimated Number of Participants
-
Taiwan
40 participants
-
Global
1000 participants
