Clinical Trials List
Protocol Number221AD301
NCT Number(ClinicalTrials.gov Identfier)NCT02477800
2015-12-01 - 2021-12-31
Phase III
Terminated7
ICD-10G30.9
Alzheimer's disease, unspecified
ICD-10G30
Alzheimer's disease
ICD-9331.0
Alzheimer's disease
A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Aducanumab (BIIB037) in Subjects with Early Alzheimer′s Disease
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Trial Applicant
IQVIA RDS Taiwan Ltd.
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Sponsor
Biogen Idec Research Limited
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- TA-FU CHEN Division of Neurology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 陳韋達 無
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
Audit
CRO
Co-Principal Investigator
- Yuan-Han Yang Division of Neurology
- 吳孟霓 Division of Neurology
- Chien-Hsun Li Division of Neurology
- Chiou-Lian Lai Division of Neurology
- Cheng-Fang Hsieh Division of Neurology
- MEI-CHUAN CHOU Division of Neurology
- PING SONG CHOU Division of Neurology
The Actual Total Number of Participants Enrolled
1 Stop recruiting
Audit
CRO
Condition/Disease
Alzheimer′s disease
Objectives
<Miracle Control Period>
The main purpose of this experiment is to determine the benchmark. In the early AD information, estimate the cognitive and dysfunctional effects sent to one each month (CDR-SB change supplement)
<Long-term tensile test>
The purpose is to estimate the long-term safety and tolerability profile of aducanumab in the early stage of AD in the United States, and to evaluate the long-term efficacy of aducanumab treatment (measurement is the measurement and the clinical, imaging and additional evaluation items notified by the information provider/care partner )
Test Drug
Aducanumab
Active Ingredient
Aducanumab
Dosage Form
Intravenous drip
Dosage
200mg
Endpoints
The main evaluation indicators are: the change in the CDR-SB score compared to the baseline at the 78th week.
The secondary evaluation indicators are as follows:
MMSE: The change in MMSE score compared to the baseline at week 78
·Alzheimer's Disease Assessment Scale-Cognitive Subscale (13 questions) [ADAS Cog 13]: The change in ADAS-Cog 13 compared to the baseline at week 78
·Alzheimer's Disease Cooperative Research-Daily Activity Checklist (Mild Cognitive Impairment Version) [ADCS-ADL-MCI]: ADCS-ADI-MCI score at week 78 compared to the baseline
The measurement indicators are the clinical, imaging and additional evaluation items notified by the subject and the information provider/care partner
Inclution Criteria
Inclusion conditions
Candidates must meet the following qualifications at the time of selection or at the time specified by the individual qualifications below to be eligible to participate in this trial:
1. Able to understand the purpose and risks of this trial, and follow national and local subjects’ privacy regulations, sign the subject’s consent form and the authorization form for use of confidential health information and specify the date.
2. When signing the consent form of the subject, the age ranged from 50 to 85 years old (inclusive).
3. All fertile women and all men must implement effective contraceptive measures during the trial period and within 24 weeks after the last dose of trial treatment.
4. At least 6 years of school or work experience is required to rule out mental deficits other than mild cognitive impairment (MCI) or mild Alzheimer's disease.
5. Must be positive for amyloid on positron tomography (PET) scan. For subjects who did not participate in the PET group, the PET scan images obtained previously (within 12 months before screening) are allowed. Previously obtained PET scan images must be sent to the central imaging inspection provider to confirm that the images meet the trial inclusion conditions.
6. Must meet all the following NIA-AA standards [Albert 2011; McKhann 2011] to diagnose "mild cognitive impairment caused by Alzheimer's disease" or "mild Alzheimer's disease" clinical conditions, and Meet the following conditions:
a. The total score of the Clinical Dementia Scale (CDR) is 0.5.
b. Reproducible Neuropsychological State Assessment Scale (RBANS) score ≤ 85, representing objectively suffering from cognitive impairment.
c. The Mini Mental State Test (MMSE) score is between 24 and 30 (inclusive).
7. In addition to the early clinical diagnosis of Alzheimer's disease, the subjects must have good health conditions (to be judged by the trial host based on the medical history and evaluation during the screening period).
8. Must agree to accept apolipoprotein E (ApoE) genotyping.
9. There is an information provider/care partner who has been determined by the trial host to have frequent and sufficient contact with the subject and therefore can provide accurate information on the subject’s cognitive and functional capabilities. The information provider/care partner must at least be able to provide information about the subject to the trial host and trial staff via telephone, and must agree to participate in person in the office visit that requires the partner to fill out the scale. There should be an information provider/care partner throughout the trial, and this trial encourages the use of the same information provider/care partner throughout the trial.
Candidates must meet the following qualifications at the time of selection or at the time specified by the individual qualifications below to be eligible to participate in this trial:
1. Able to understand the purpose and risks of this trial, and follow national and local subjects’ privacy regulations, sign the subject’s consent form and the authorization form for use of confidential health information and specify the date.
2. When signing the consent form of the subject, the age ranged from 50 to 85 years old (inclusive).
3. All fertile women and all men must implement effective contraceptive measures during the trial period and within 24 weeks after the last dose of trial treatment.
4. At least 6 years of school or work experience is required to rule out mental deficits other than mild cognitive impairment (MCI) or mild Alzheimer's disease.
5. Must be positive for amyloid on positron tomography (PET) scan. For subjects who did not participate in the PET group, the PET scan images obtained previously (within 12 months before screening) are allowed. Previously obtained PET scan images must be sent to the central imaging inspection provider to confirm that the images meet the trial inclusion conditions.
6. Must meet all the following NIA-AA standards [Albert 2011; McKhann 2011] to diagnose "mild cognitive impairment caused by Alzheimer's disease" or "mild Alzheimer's disease" clinical conditions, and Meet the following conditions:
a. The total score of the Clinical Dementia Scale (CDR) is 0.5.
b. Reproducible Neuropsychological State Assessment Scale (RBANS) score ≤ 85, representing objectively suffering from cognitive impairment.
c. The Mini Mental State Test (MMSE) score is between 24 and 30 (inclusive).
7. In addition to the early clinical diagnosis of Alzheimer's disease, the subjects must have good health conditions (to be judged by the trial host based on the medical history and evaluation during the screening period).
8. Must agree to accept apolipoprotein E (ApoE) genotyping.
9. There is an information provider/care partner who has been determined by the trial host to have frequent and sufficient contact with the subject and therefore can provide accurate information on the subject’s cognitive and functional capabilities. The information provider/care partner must at least be able to provide information about the subject to the trial host and trial staff via telephone, and must agree to participate in person in the office visit that requires the partner to fill out the scale. There should be an information provider/care partner throughout the trial, and this trial encourages the use of the same information provider/care partner throughout the trial.
Exclusion Criteria
Exclude conditions
Candidates are not allowed to enter this trial if they have any of the following exclusions at the time of screening or at the time specified by the following individual conditions:
Medical history:
1. Any uncontrolled medical treatment or neurological/neurodegenerative conditions (excluding Alzheimer’s disease), which may be the cause of cognitive impairment by the test host (for example: drug abuse, vitamin B12 deficiency, Abnormal thyroid function, stroke or other cardiovascular conditions, Lewy body dementia, frontotemporal dementia, head trauma).
2. Suffered from a clinically significant mental illness (for example: uncontrolled major depression, schizophrenia, bipolar disorder) within 6 months before screening.
3. A transient ischemic attack or stroke, or any unexplainable loss of consciousness occurred within 1 year before screening.
4. In the brain magnetic resonance imaging (MRI) (interpreted by the central unit) during the screening, there is evidence of any of the following:
a. Acute or subacute bleeding.
b. Previous major hemorrhage (defined as a diameter >1 cm on the T2* sequence), unless it can be proven that this finding is not caused by the underlying structure or blood vessel abnormalities (that is, this finding does not mean that the subject has recurred bleeding risks of).
c. There are more than 4 small bleedings (defined as diameter> 1 cm on the T2* sequence).
d. Cortical infarction (defined as diameter> 1.5 cm).
e. There is a small gap infarction at >1 (defined as diameter> 1.5 cm).
f. Suffering from epidermal iron deposition.
g. A history of diffuse white matter disease, defined as a score of 3 on the Age-Related White Matter Change Scale [Walund 2001].
h. There are any findings that, as determined by the trial host, may be the contributing cause of the subject’s dementia, may bring risks to the subject, or may result in the inability to obtain satisfactory MRI evaluation results in safety monitoring .
5. Have a history of bleeding disorders, or have a condition or thrombus that can easily lead to bleeding, or obtain clinically significant abnormal results in the coagulation function test at the time of screening (as determined by the trial host).
6. Diabetes with poorly controlled conditions is defined as: (according to the definition of the National Association for Glycated Hemoglobin Standardization) The value of glycated hemoglobin (HbA1c)> 7%.
7. Unstable angina, myocardial infarction, chronic heart failure (New York Heart Association grade III or IV), or clinically significant conduction abnormalities (such as unstable atrial fibrillation) occurred within 1 year before screening.
8. A 12-lead electrocardiogram (ECG) with clinically significant abnormalities (determined by the trial leader).
9. Suffering from uncontrolled hypertension, defined as: the average of 3 systolic blood pressure [SBP]/diastolic blood pressure [DBP] values at the time of screening> 165/100 mmHg (If the blood pressure measurement exceeds this upper limit, it can be The test host retests if it is necessary, but the value must fall within the specified range before the subject is eligible to participate in the test), or the test continues to be >180 within 3 months before random assignment (day 1) /100 mmHg SBP/DBP value, and the test host determined that it represents chronic uncontrolled hypertension.
10. There is a history of malignant tumor or cancer. After discussing with the trial client, the following cases may allow exceptions:
• Subjects whose cancer has been in remission for more than 5 years before screening.
• Subjects whose basal cell carcinoma or squamous cell carcinoma has been removed or treated.
• Subjects with prostate cancer in situ.
11. Epilepsy occurred within 10 years before screening.
12. There are signs of liver function impairment: abnormal liver function test results during screening (for example, repeated measurements show that aspartate transamine [AST] and alanine transamine [ALT] >2 times the upper limit of normal)
13. Suffered in the past, or there is evidence that it is currently suffering from an autoimmune disease (confirmed by the trial host as clinically significant, or requiring long-term use of systemic corticosteroids or other immunosuppressive agents).
14. Recent (within 1 year before screening) a record of alcohol or drug abuse (as determined by the trial host), a positive urine drug (caused by over-the-counter drugs) or alcohol screening at the time of screening, or use of cannabinoids (prescription or entertainment) Sexual use).
15. Patients with clinically significant systemic diseases or severe infections (such as pneumonia, sepsis) within 30 days before screening or during screening.
16. Have a history of infection with human immunodeficiency virus (HIV), or a positive test result.
17. Hepatitis C virus antibody or hepatitis B virus (defined as hepatitis B surface antigen [HBsAg] or hepatitis B core antibody [HBcAb] positive) has been detected, or the test result was positive at the time of screening. Subjects who have previously been immune to hepatitis B due to natural infection (defined as HBsAb negative, hepatitis B surface antigen IgG positive, and HBcAb positive) will be eligible to participate in this trial (according to the US Department of Disease Control Interpretation method of hepatitis serological test series).
18. There is a history of severe allergies or systemic allergic reactions, or a record of allergies to any of the inactive ingredients in the medicine.
19. Suffer from any other unstable or uncontrolled medical condition (such as kidney disease) that is deemed by the trial host to affect the safety of the subject or interfere with the evaluation of the trial.
drug:
20. There are any drugs that, as determined by the trial host, may affect cognitive impairment, increase the risk of adverse events in the subject, or impair the ability of the subject to perform cognitive tests or complete the test procedures.
21. At least 4 weeks before the first visit in the screening period, the long-term medication allowed by this test has not been used at a stable dose; or at least 8 weeks before the first visit in the screening period, Azhai has not been used at a stable dose Medications for silent disease (including but not limited to donepezil, rivastigmine, galantamine, tacrine and memantine).
22. Use drugs with anti-platelet aggregation or anti-coagulation properties (but it is allowed to use aspirin at a preventive dose [>325 mg/day]).
23. Use illegal narcotic drugs.
24. Have been vaccinated within 10 days before random assignment (day 1).
25. Participated in any active immunotherapy trial with β-amyloid as the target, unless there is evidence that the patient received a placebo.
26. In the 48 weeks before screening, have participated in any other passive immunotherapy trials with β-amyloid as the target, unless there is evidence that the patient received a placebo.
27. Participated in any trial that is said to have a palliative effect on Alzheimer’s disease within 26 weeks before screening, unless there is evidence that the patient received a placebo. Subjects with amyloid-related imaging abnormalities-exudative manifestations (ARIA-E) found in previous trials of alleviating diseases should be excluded from this trial.
28. Participated in a trial using aducanumab (subjects who have not received active aducanumab treatment are still eligible to take the test).
Test procedure:
29. There are contraindications and cannot accept brain MRI (for example: heart rhythm regulator; aneurysm clips, artificial heart valves, or other metal foreign bodies that are incompatible with MRI; suffering from claustrophobia that cannot be controlled by medical methods).
30. Have contraindications and cannot accept PET scans (for example: unable to lie down or stand still during the entire scan), or unable to tolerate previous PET scans (ie, have had an allergic reaction to any PET ligand or imaging agent in the past) , Or failed to participate and cooperate in the previous PET scan).
31. In the 24 weeks before the screening, any PET scan with amyloid as the target ligand obtained a negative result.
32. Have received or planned to receive experimental radiation exposure within 12 months before screening, so if you participate in this trial again, the upper limit of radiation dose will be exceeded.
33. For subjects who agree to receive lumbar puncture (LP), there are any contraindications and cannot receive lumbar puncture (for example: platelet count <100,000/microliter (μL), lumbar deformity). Any symptoms caused by or related to the selective lumbar puncture performed during the screening period must be relieved before random assignment. Even if they cannot participate in the selective lumbar puncture part, subjects can still participate in the overall trial.
other:
34. Female subjects who are pregnant or breastfeeding.
35. Participate in this trial previously. Subjects who fail the screening will have the opportunity to undergo another screening at the decision of the trial commissioner, but exclude those who failed the screening due to abnormal PET, MMSE, CDR, hepatitis B or C, or abnormal MRI results.
36. The subject currently lives in a systematic care facility and receives a lot of intervention and/or support in daily activities.
37. Donated blood (> 1 unit) within 1 month before screening.
38. Failure to comply with the test regulations.
39. For other unspecified reasons, the test host or Biogen determines that the subject is not suitable for entering this test.
Candidates are not allowed to enter this trial if they have any of the following exclusions at the time of screening or at the time specified by the following individual conditions:
Medical history:
1. Any uncontrolled medical treatment or neurological/neurodegenerative conditions (excluding Alzheimer’s disease), which may be the cause of cognitive impairment by the test host (for example: drug abuse, vitamin B12 deficiency, Abnormal thyroid function, stroke or other cardiovascular conditions, Lewy body dementia, frontotemporal dementia, head trauma).
2. Suffered from a clinically significant mental illness (for example: uncontrolled major depression, schizophrenia, bipolar disorder) within 6 months before screening.
3. A transient ischemic attack or stroke, or any unexplainable loss of consciousness occurred within 1 year before screening.
4. In the brain magnetic resonance imaging (MRI) (interpreted by the central unit) during the screening, there is evidence of any of the following:
a. Acute or subacute bleeding.
b. Previous major hemorrhage (defined as a diameter >1 cm on the T2* sequence), unless it can be proven that this finding is not caused by the underlying structure or blood vessel abnormalities (that is, this finding does not mean that the subject has recurred bleeding risks of).
c. There are more than 4 small bleedings (defined as diameter> 1 cm on the T2* sequence).
d. Cortical infarction (defined as diameter> 1.5 cm).
e. There is a small gap infarction at >1 (defined as diameter> 1.5 cm).
f. Suffering from epidermal iron deposition.
g. A history of diffuse white matter disease, defined as a score of 3 on the Age-Related White Matter Change Scale [Walund 2001].
h. There are any findings that, as determined by the trial host, may be the contributing cause of the subject’s dementia, may bring risks to the subject, or may result in the inability to obtain satisfactory MRI evaluation results in safety monitoring .
5. Have a history of bleeding disorders, or have a condition or thrombus that can easily lead to bleeding, or obtain clinically significant abnormal results in the coagulation function test at the time of screening (as determined by the trial host).
6. Diabetes with poorly controlled conditions is defined as: (according to the definition of the National Association for Glycated Hemoglobin Standardization) The value of glycated hemoglobin (HbA1c)> 7%.
7. Unstable angina, myocardial infarction, chronic heart failure (New York Heart Association grade III or IV), or clinically significant conduction abnormalities (such as unstable atrial fibrillation) occurred within 1 year before screening.
8. A 12-lead electrocardiogram (ECG) with clinically significant abnormalities (determined by the trial leader).
9. Suffering from uncontrolled hypertension, defined as: the average of 3 systolic blood pressure [SBP]/diastolic blood pressure [DBP] values at the time of screening> 165/100 mmHg (If the blood pressure measurement exceeds this upper limit, it can be The test host retests if it is necessary, but the value must fall within the specified range before the subject is eligible to participate in the test), or the test continues to be >180 within 3 months before random assignment (day 1) /100 mmHg SBP/DBP value, and the test host determined that it represents chronic uncontrolled hypertension.
10. There is a history of malignant tumor or cancer. After discussing with the trial client, the following cases may allow exceptions:
• Subjects whose cancer has been in remission for more than 5 years before screening.
• Subjects whose basal cell carcinoma or squamous cell carcinoma has been removed or treated.
• Subjects with prostate cancer in situ.
11. Epilepsy occurred within 10 years before screening.
12. There are signs of liver function impairment: abnormal liver function test results during screening (for example, repeated measurements show that aspartate transamine [AST] and alanine transamine [ALT] >2 times the upper limit of normal)
13. Suffered in the past, or there is evidence that it is currently suffering from an autoimmune disease (confirmed by the trial host as clinically significant, or requiring long-term use of systemic corticosteroids or other immunosuppressive agents).
14. Recent (within 1 year before screening) a record of alcohol or drug abuse (as determined by the trial host), a positive urine drug (caused by over-the-counter drugs) or alcohol screening at the time of screening, or use of cannabinoids (prescription or entertainment) Sexual use).
15. Patients with clinically significant systemic diseases or severe infections (such as pneumonia, sepsis) within 30 days before screening or during screening.
16. Have a history of infection with human immunodeficiency virus (HIV), or a positive test result.
17. Hepatitis C virus antibody or hepatitis B virus (defined as hepatitis B surface antigen [HBsAg] or hepatitis B core antibody [HBcAb] positive) has been detected, or the test result was positive at the time of screening. Subjects who have previously been immune to hepatitis B due to natural infection (defined as HBsAb negative, hepatitis B surface antigen IgG positive, and HBcAb positive) will be eligible to participate in this trial (according to the US Department of Disease Control Interpretation method of hepatitis serological test series).
18. There is a history of severe allergies or systemic allergic reactions, or a record of allergies to any of the inactive ingredients in the medicine.
19. Suffer from any other unstable or uncontrolled medical condition (such as kidney disease) that is deemed by the trial host to affect the safety of the subject or interfere with the evaluation of the trial.
drug:
20. There are any drugs that, as determined by the trial host, may affect cognitive impairment, increase the risk of adverse events in the subject, or impair the ability of the subject to perform cognitive tests or complete the test procedures.
21. At least 4 weeks before the first visit in the screening period, the long-term medication allowed by this test has not been used at a stable dose; or at least 8 weeks before the first visit in the screening period, Azhai has not been used at a stable dose Medications for silent disease (including but not limited to donepezil, rivastigmine, galantamine, tacrine and memantine).
22. Use drugs with anti-platelet aggregation or anti-coagulation properties (but it is allowed to use aspirin at a preventive dose [>325 mg/day]).
23. Use illegal narcotic drugs.
24. Have been vaccinated within 10 days before random assignment (day 1).
25. Participated in any active immunotherapy trial with β-amyloid as the target, unless there is evidence that the patient received a placebo.
26. In the 48 weeks before screening, have participated in any other passive immunotherapy trials with β-amyloid as the target, unless there is evidence that the patient received a placebo.
27. Participated in any trial that is said to have a palliative effect on Alzheimer’s disease within 26 weeks before screening, unless there is evidence that the patient received a placebo. Subjects with amyloid-related imaging abnormalities-exudative manifestations (ARIA-E) found in previous trials of alleviating diseases should be excluded from this trial.
28. Participated in a trial using aducanumab (subjects who have not received active aducanumab treatment are still eligible to take the test).
Test procedure:
29. There are contraindications and cannot accept brain MRI (for example: heart rhythm regulator; aneurysm clips, artificial heart valves, or other metal foreign bodies that are incompatible with MRI; suffering from claustrophobia that cannot be controlled by medical methods).
30. Have contraindications and cannot accept PET scans (for example: unable to lie down or stand still during the entire scan), or unable to tolerate previous PET scans (ie, have had an allergic reaction to any PET ligand or imaging agent in the past) , Or failed to participate and cooperate in the previous PET scan).
31. In the 24 weeks before the screening, any PET scan with amyloid as the target ligand obtained a negative result.
32. Have received or planned to receive experimental radiation exposure within 12 months before screening, so if you participate in this trial again, the upper limit of radiation dose will be exceeded.
33. For subjects who agree to receive lumbar puncture (LP), there are any contraindications and cannot receive lumbar puncture (for example: platelet count <100,000/microliter (μL), lumbar deformity). Any symptoms caused by or related to the selective lumbar puncture performed during the screening period must be relieved before random assignment. Even if they cannot participate in the selective lumbar puncture part, subjects can still participate in the overall trial.
other:
34. Female subjects who are pregnant or breastfeeding.
35. Participate in this trial previously. Subjects who fail the screening will have the opportunity to undergo another screening at the decision of the trial commissioner, but exclude those who failed the screening due to abnormal PET, MMSE, CDR, hepatitis B or C, or abnormal MRI results.
36. The subject currently lives in a systematic care facility and receives a lot of intervention and/or support in daily activities.
37. Donated blood (> 1 unit) within 1 month before screening.
38. Failure to comply with the test regulations.
39. For other unspecified reasons, the test host or Biogen determines that the subject is not suitable for entering this test.
The Estimated Number of Participants
-
Taiwan
45 participants
-
Global
1350 participants
