Clinical Trials List
Protocol NumberWN29922
NCT Number(ClinicalTrials.gov Identfier)NCT03444870
Completed
2018-06-01 - 2023-03-21
Phase III
Terminated6
ICD-10F03.90
Unspecified dementia without behavioral disturbance
ICD-10G30
Alzheimer's disease
A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of Gantenerumab in Patients With Early (Prodromal to Mild) Alzheimer's Disease
-
Trial Applicant
-
Sponsor
Hoffmann-La Roche
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Ming-Kuei Lu Division of Neurology
- Ching-Hua Lu Lu Division of Neurology
- Jui-Cheng Chen Division of Neurology
- Wei-Shih Huang Division of Neurology
- Kuan-Fei Chen Division of Neurology
- Kang-Hsu Lin Division of Neurology
- Hui-Chun Huang Division of Neurology
- Yuh-Cherng Guo Division of Neurology
- Chon-Haw Tsai Division of Neurology
- Yi-Ting Hsu Division of Neurology
- Fu-Yu Lin Division of Neurology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
CRO
Linkou Chang Gung Medical Foundation
Taiwan National PI
黃錦章
Co-Principal Investigator
- KuoLun Huang Division of Neurology
- Kun-Ju Lin Division of Nuclear Medicine
- Tzu-Chen Yen Division of Nuclear Medicine
The Actual Total Number of Participants Enrolled
2 Terminated
Audit
None
Co-Principal Investigator
Audit
CRO
Co-Principal Investigator
- 高伊慧 Division of Neurology
- YA-FANG CHEN Division of Radiology
- TA-FU CHEN Division of Neurology
- RUOH-FANG YEN Division of Nuclear Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- Chien-Hsun Li Division of Neurology
- Chiou-Lian Lai Division of Neurology
- 吳孟霓 Division of Neurology
- Ching-Kuan Liu Division of Neurology
- Cheng-Fang Hsieh Division of Neurology
- PING SONG CHOU Division of Neurology
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Alzheimer Disease
Objectives
This randomized, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy and safety of gantenerumab versus placebo in participants with early (prodromal to mild) AD. All participants must show evidence of beta-amyloid pathology. Eligible participants will be randomized 1:1 to receive either subcutaneous (SC) injection of gantenerumab or placebo. The primary efficacy assessment will be performed at the end of the double blind period at week 116. Participants will then be offered to enter into an open-label extension (OLE). Participants not willing to go to the OLE will participate in a long term follow-up period for up to 50 weeks after the last gantenerumab dose.
Test Drug
GANTENERUMAB
Active Ingredient
GANTENERUMAB
Dosage Form
injection
Dosage
300mg/2.0mL
Endpoints
- The change from baseline (Day 1) to Week 104 in global outcome, as measured by the CDR-SOB
- The change from baseline to Week 104 in cognition, as measured by the ADAS-Cog11
-The change from baseline to Week 104 in cognition
and/or function, as measured by:
• MMSE total score
• ADAS-Cog13
• Verbal Fluency Task
• FAQ
• ADCS-ADL total score
- The change from baseline to Week 104 in cognition, as measured by the ADAS-Cog11
-The change from baseline to Week 104 in cognition
and/or function, as measured by:
• MMSE total score
• ADAS-Cog13
• Verbal Fluency Task
• FAQ
• ADCS-ADL total score
Inclution Criteria
Inclusion Criteria
Patients must meet the following criteria for study entry:
• Ability to provide written consent signed by the patient (co-signed by the patient’s
legally authorized representative, if required by the local regulations, guidelines, and
independent Ethics Committee [EC] or Institutional Review Board [IRB])
• Age 50−90 years old at screening, inclusive
• Availability of a person (referred to as the “study partner” throughout this protocol)
who in the investigator's judgment:
– Has frequent and sufficient contact (e.g., 5 times per week or approximately
10 hours per week) with the patient to be able to provide accurate information
regarding the patient’s cognitive and functional abilities, agrees to provide
information at clinic visits (which require partner input for scale completion), signs
the necessary Informed Consent Form(s), and has sufficient cognitive capacity to
accurately report on the patient’s behavior and cognitive and functional abilities
– Is in sufficiently good general health to have a high likelihood of maintaining the
same level of interaction with the patient and participation in study procedures
throughout the duration of the study
Every effort should be made to have same study partner participate throughout
the duration of the study.
• Fluency in the language of the tests used at the study site
• Willingness and ability to complete all aspects of the study (including MRI, lumbar
puncture [if applicable], clinical genotyping, and PET imaging [if applicable])
The patient should be capable of completing assessments either alone or with
the help of the study partner.
• Adequate visual and auditory acuity, in the investigator’s judgment, sufficient to
perform the neuropsychological testing (eye glasses and hearing aids are permitted)
• Evidence of AD pathological process, as confirmed by CSF tau/Aβ42 or on amyloid
PET scan by qualitative read by the core/central PET laboratory
• Demonstrated abnormal memory function at screening (FCSRT cueing
index ≤0.67 and free recall ≤27)
• Screening MMSE score ≥ 20 and CDR-GS of 0.5 or 1.0
• Probable AD dementia (consistent with NIA/AA core clinical criteria for probable AD
dementia) (McKhann et al. 2011) or prodromal AD (consistent with the NIA/AA
diagnostic criteria and guidelines for mild cognitive decline due to AD) (Albert et al.
2011)
• If the patient is receiving symptomatic AD medications, a stable dosing regimen for
at least 3 months prior to baseline and until randomization
• Agreement not to donate blood or blood products for transfusion for the duration of
the study and for 1 year after final dose of study drug
• Agreement not to participate in other research studies for the duration of this trial
and its associated substudies
• For enrollment in the China extension study, residency in the People’s Republic
of China
• For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods that result in a failure rate
of <1% per year during the treatment period and for at least 8 weeks after the last
dose of study drug
A woman is considered to be of childbearing potential if she is postmenarcheal,
has not reached a postmenopausal state (≥12 continuous months of amenorrhea
with no identified cause other than menopause), and has not undergone surgical
sterilization (removal of ovaries and/or uterus).
Examples of contraceptive methods with a failure rate of <1% per year include
bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit
ovulation, hormone-releasing intrauterine devices, and copper intrauterine
devices.
The reliability of sexual abstinence should be evaluated in relation to the duration
of the clinical trial and the preferred and usual lifestyle of the patient. Periodic
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods)
and withdrawal are not acceptable methods of contraception.
Patients must meet the following criteria for study entry:
• Ability to provide written consent signed by the patient (co-signed by the patient’s
legally authorized representative, if required by the local regulations, guidelines, and
independent Ethics Committee [EC] or Institutional Review Board [IRB])
• Age 50−90 years old at screening, inclusive
• Availability of a person (referred to as the “study partner” throughout this protocol)
who in the investigator's judgment:
– Has frequent and sufficient contact (e.g., 5 times per week or approximately
10 hours per week) with the patient to be able to provide accurate information
regarding the patient’s cognitive and functional abilities, agrees to provide
information at clinic visits (which require partner input for scale completion), signs
the necessary Informed Consent Form(s), and has sufficient cognitive capacity to
accurately report on the patient’s behavior and cognitive and functional abilities
– Is in sufficiently good general health to have a high likelihood of maintaining the
same level of interaction with the patient and participation in study procedures
throughout the duration of the study
Every effort should be made to have same study partner participate throughout
the duration of the study.
• Fluency in the language of the tests used at the study site
• Willingness and ability to complete all aspects of the study (including MRI, lumbar
puncture [if applicable], clinical genotyping, and PET imaging [if applicable])
The patient should be capable of completing assessments either alone or with
the help of the study partner.
• Adequate visual and auditory acuity, in the investigator’s judgment, sufficient to
perform the neuropsychological testing (eye glasses and hearing aids are permitted)
• Evidence of AD pathological process, as confirmed by CSF tau/Aβ42 or on amyloid
PET scan by qualitative read by the core/central PET laboratory
• Demonstrated abnormal memory function at screening (FCSRT cueing
index ≤0.67 and free recall ≤27)
• Screening MMSE score ≥ 20 and CDR-GS of 0.5 or 1.0
• Probable AD dementia (consistent with NIA/AA core clinical criteria for probable AD
dementia) (McKhann et al. 2011) or prodromal AD (consistent with the NIA/AA
diagnostic criteria and guidelines for mild cognitive decline due to AD) (Albert et al.
2011)
• If the patient is receiving symptomatic AD medications, a stable dosing regimen for
at least 3 months prior to baseline and until randomization
• Agreement not to donate blood or blood products for transfusion for the duration of
the study and for 1 year after final dose of study drug
• Agreement not to participate in other research studies for the duration of this trial
and its associated substudies
• For enrollment in the China extension study, residency in the People’s Republic
of China
• For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods that result in a failure rate
of <1% per year during the treatment period and for at least 8 weeks after the last
dose of study drug
A woman is considered to be of childbearing potential if she is postmenarcheal,
has not reached a postmenopausal state (≥12 continuous months of amenorrhea
with no identified cause other than menopause), and has not undergone surgical
sterilization (removal of ovaries and/or uterus).
Examples of contraceptive methods with a failure rate of <1% per year include
bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit
ovulation, hormone-releasing intrauterine devices, and copper intrauterine
devices.
The reliability of sexual abstinence should be evaluated in relation to the duration
of the clinical trial and the preferred and usual lifestyle of the patient. Periodic
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods)
and withdrawal are not acceptable methods of contraception.
Exclusion Criteria
Key Exclusion criteria:
Any evidence of a condition other than AD that may affect cognition
History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder
History or presence of clinically evident systemic vascular disease that in the opinion of the investigator has the potential to affect cognitive function
History or presence of clinically evident cerebrovascular disease
History or presence of posterior reversible encephalopathy syndrome
History or presence of any stroke with clinical symptoms within the past 12 months, or documented history within the last 6 months of an acute event that is consistent with a transient ischemic attack
History of severe, clinically significant CNS trauma
History or presence of intracranial mass (e.g., glioma, meningioma) that could potentially impair cognition
Presence of infections that affect brain function or history of infections that resulted in neurologic sequelae
History or presence of systemic autoimmune disorders that potentially cause progressive neurologic disease with associated cognitive deficits
At risk for suicide in the opinion of the investigator
Alcohol and/or substance abuse or dependants in past 2 years
Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities
Any contraindications to brain MRI
Unstable or clinically significant cardiovascular, kidney or liver disease
Uncontrolled hypertension
Unstable or clinically significant cardiovascular disease
Abnormal thyroid function
Patients with evidence of folic acid deficiency
Exclusion for Open-Label Extension (OLE):
Discontinued from study treatment during the double-blind treatment period
Received any other investigational medication during the double-blind treatment period or after the end of double-blind treatment
Participation in the OLE deemed inappropriate by the investigator
Presence of ARIA-E findings at the Week 104 MRI scan
Any evidence of a condition other than AD that may affect cognition
History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder
History or presence of clinically evident systemic vascular disease that in the opinion of the investigator has the potential to affect cognitive function
History or presence of clinically evident cerebrovascular disease
History or presence of posterior reversible encephalopathy syndrome
History or presence of any stroke with clinical symptoms within the past 12 months, or documented history within the last 6 months of an acute event that is consistent with a transient ischemic attack
History of severe, clinically significant CNS trauma
History or presence of intracranial mass (e.g., glioma, meningioma) that could potentially impair cognition
Presence of infections that affect brain function or history of infections that resulted in neurologic sequelae
History or presence of systemic autoimmune disorders that potentially cause progressive neurologic disease with associated cognitive deficits
At risk for suicide in the opinion of the investigator
Alcohol and/or substance abuse or dependants in past 2 years
Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities
Any contraindications to brain MRI
Unstable or clinically significant cardiovascular, kidney or liver disease
Uncontrolled hypertension
Unstable or clinically significant cardiovascular disease
Abnormal thyroid function
Patients with evidence of folic acid deficiency
Exclusion for Open-Label Extension (OLE):
Discontinued from study treatment during the double-blind treatment period
Received any other investigational medication during the double-blind treatment period or after the end of double-blind treatment
Participation in the OLE deemed inappropriate by the investigator
Presence of ARIA-E findings at the Week 104 MRI scan
The Estimated Number of Participants
-
Taiwan
30 participants
-
Global
1016 participants
