APN-1607 global Phase 2 study in Alzheimer disease

JRCT ID: jRCT2031210713

Registered date:31/03/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Alzheimer disease and mild cognitive impairment due to Alzheimer disease
• Date of first enrollment: 02/03/2022
• Target sample size: 20
• Countries of recruitment: United States,Japan,Taiwan,Japan
• Study type: Interventional
• Intervention(s): PET imaging

Outcome(s)

• Primary Outcome: Tau PET imaging, amyloid PET imaging, MRI
• Secondary Outcome: Vital signs, ECG, blood chemisry

Key inclusion & exclusion criteria

• Age minimum: >= 50age old
• Age maximum: <= 85age old
• Gender: Both

Include criteria

All subjects eligible for inclusion in this study must fulfill all of the following criteria:
1. Males or females aged 50 to 85 years, inclusive.
2. Female subjects must be documented by medical records or physician note to be either surgically sterile (by means of hysterectomy, bilateral oophorectomy, or tubal ligation) or post-menopausal for at least 1 year (ie, 12 consecutive months with no menses without an alternative medical cause) or, if they are of childbearing potential, must commit to using a barrier contraception method or to abstinence for the duration of the study and must have a negative pregnancy test.
3. Male subjects and their partners of childbearing potential must commit to the use of two methods of contraception, one of which is a barrier method (ie, condom), or to abstinence for the study duration.
4. Male subjects must not donate sperm for the study duration.
5. Willing and able to participate in all study procedures.
Additional inclusion criteria for healthy subjects:
1. Written informed consent must be obtained before any assessment is performed.
2. Medically healthy with no clinically relevant finding on physical examination, laboratory profiles, VS, or ECG at screening and upon reporting for the 18F-APN-1607 Imaging visit.
3. No cognitive impairment based on neuropsychological battery and as judged by the
Investigator.
4. No first-degree family history of early-onset AD or neurodegenerative disease associated with dementia (prior to age 65).
5. Has a clinical dementia rating (CDR) score of 0.
6. Has an MMSE score more than 27.
7. The subject has an appropriate informant to accompany the subject to screening to provide information for CDR testing. In the event that the informant cannot accompany the subjectto screening, the interview may be performed via phone, at the discretion of the site investigator.
Additional inclusion criteria for subjects with MDAD:
1. Written informed consent must be obtained before any assessment is performed.
2. Must meet all of the clinical criteria for MCI according to NIA-AA criteria, including lack of functional impairment sufficient to warrant a diagnosis of dementia.
3. Has a CDR score 0.5.
4. Has an MMSE score between 24 and 30, inclusive.
5. Has a positive amyloid PET scan obtained during screening or in the past 1 year.
6. Medications taken for symptomatic treatment of AD must have been stable for at least 30 days prior to screening and throughout the completion of the neuro- psychological battery.
7. The subject has an appropriate informant to provide information for the CDR and
accompany the subject for any visits, if required for subject or staff comfort or safety.
Additional inclusion criteria for subjects with AD dementia:
1. Written informed consent must be obtained before any assessment is performed. If in the investigator opinion the patient lacks capacity to consent, participation is only possible if the subject has a LAR or responsible next-of-kin and that individual provides written informed consent in accordance with local regulations and guidelines and the rules of the applicable IEC/IRB. When written informed consent is provided by a LAR or responsible next of kin, the subject assent must also be obtained and documented. For subjects judged lacking capacity to consent, next-of-kin consent in lieu of LAR consent is only allowed where permitted by local laws and regulations.
2. Has a diagnosis of AD dementia according to NIA-AA criteria, including a significant
impairment of activities of daily living.
3. Has a CDR score more than 0.5 at screening.
4. Has an MMSE score between 10 and 26, inclusive.
5. Has a positive amyloid PET scan obtained during screening or in the past 1 year.
6. Medications taken for symptomatic treatment of AD must have been stable for 30 days prior to screening and throughout the completion of the neuropsychological battery.
7. The subject has an appropriate informant to accompany the subject on all visits and
provide information for the CDR.

Exclude criteria

Any subject fulfilling any of the following criteria are not eligible for inclusion in this
study:
1. Current or prior history (within the last 10 years) of alcohol or drug abuse.
2. Known hypersensitivity to 18F-APN-1607 or its excipients.
3. Clinically significant active or unstable medical illness or planned surgical procedures during the study period. History of cancer (other than non-melanoma skin cancers or stable, local prostate cancer), unless without evidence of active disease within the last 3 years and without ongoing medical or surgical therapy.
4. Laboratory tests with clinically significant abnormalities or a history or evidence of
clinically significant unstable medical illness.
5. Has received any investigational drug or device for any purpose within 30 days of
screening (or 5 half-lives of the drug, whichever is longer), has received a non-biologic
investigational treatment (ie, small molecule) for AD or other cause of dementia within
the last 3 months (or 5 half-lives of the drug, whichever is longer), or received a non- vaccine treatment (ie, monoclonal antibody) for the treatment of AD or other cause of
dementia within the last 6 months, or has ever received a vaccine for the treatment of AD or other cause of dementia.
6. Prior participation in other research protocols or clinical care in the last year in which the additional radiation exposure expected from participation in this clinical study will
together exceed the local guidelines, eg, above an effective dose of 50 mSv in the US.
7. Pregnant, lactating or breastfeeding.
8. Evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, alternative neurological, immunodeficiency,
pulmonary, or other disorder or disease.
9. Unsuitable veins for repeated venipuncture.
10. MRI exclusion criteria include: Findings that may be responsible for the neurologic status of the patient such as significant evidence of cerebrovascular disease (more than two lacunar infarcts, any territorial infarct more than 1cm3, or deep white matter abnormality corresponding to an overall Fazekas scale of 3 with at least one confluent hyperintense lesion on the fluid-attenuated inversion recovery (FLAIR) sequence that is more than 20 mm in any dimension), infectious disease, space-occupying lesions, normal pressure hydrocephalus or any other abnormalities associated with central nervous system (CNS) disease. For subjects with MDAD or AD dementia, there may be evidence of atrophy compatible with AD.
11. Implants, such as implanted cardiac pacemakers or defibrillators, insulin pumps, cochlear implants, metallic ocular foreign body, implanted neural stimulators, CNS aneurysm clips, and other medical implants that have not been certified for MRI, or history of claustrophobia in MRI unless an acceptable MRI obtained in the 1 year prior to participation in the study is used.
12. Signs or symptoms suggestive of active coronavirus disease 2019 (COVID-19) and/or confirmed diagnosis of COVID-19, or positive COVID-19 polymerase chain reaction (PCR) test in the previous 2 weeks. These subjects should not be enrolled until 4 weeks after full recovery and further assessment by the Investigator per institutional guidelines. A subject with a known history of being exposed to someone who was diagnosed of COVID-19, during the prior 4 weeks, should not be enrolled unless the infection is excluded by local practice or institution.
Additional exclusion criteria for healthy subjects:
1. Meets criteria for a diagnosis of MDAD or dementia or has ever had such a diagnosis.
2. Has ever received treatment with a drug for cognitive impairment or dementia.
Additional exclusion criteria for subjects with MDAD:
1. Meets criteria for a diagnosis of dementia due to AD.

Related Information

• Primary Sponsor: Miyamoto Masaomi