Clinical trial NCT03625622: Efficacy and Safety of 26-Week Treatment of AR1001 in Patients With Mild to Moderate Alzheimer's Disease
Official title: A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate Efficacy and Safety of 26-Week Treatment of AR1001 in Patients With Mild to Moderate Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mild to Moderate Alzheimer's Disease
Keywords: Alzheimer's disease
Lead sponsor: AriBio Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-08-10
Enrollment: 210
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: After the first 26 weeks, subjects can participate in an optional extension study to receive either 10 mg or 30 mg AR1001 for another 26 weeks.
Primary purpose: TREATMENT

Brief summary: A double-blinded, randomized, placebo-controlled study will be performed to evaluate the efficacy and safety of treating AR1001 in patients with mild to moderate Alzheimer's disease for 26 weeks.

Detailed description: Alzheimer's Disease (AD) is the most prevalent neurodegenerative disorder in The United States affecting approximately 5.4 million Americans. AD is characterized by progressive loss in memory and as well as a decline in the ability to learn that is associated with neuronal death. Well known hallmarks of AD are neuritic plaques and neurofibrillary tangles and extensive inflammation. Currently, no treatment has been developed to fully cure or prevent the progression of dementia that is associated with AD.

AR1001 is a polypharmacological drug candidate being developed as a treatment for AD and shows great potential with favorable attributes for a central nervous system (CNS) drug (i.e., high specificity and potency, as well as good pharmacokinetic, bioavailability, CNS penetration, and ensured safety).

The clinical study of AR1001 aims to evaluate the efficacy and safety of AR1001 as a potential treatment for AD. Based on the preclinical results, AR1001 could be an effective treatment option with a mechanism of action that has not been explored for AD indication.

Eligibility criteria: Inclusion Criteria

1. Male or female subjects aged 55-80 years at the time of signing the Informed Consent Form.
2. Subjects (or subject's legally acceptable representative) and caregiver(s) who can sign an Informed Consent to participate in the study. Same caregiver(s) must assist the subject throughout the entire duration of the study.
3. Subjects who have a diagnosis of probable Alzheimer's disease according to the NIA-AA (National Institute of Aging and Alzheimer's Associations, 2011) criteria with mild to moderate dementia (stage 4 - 5) at screening.
4. Subjects who have mild-to-moderate cognitive impairment with MMSE Score of 16-26 at screening.
5. Subjects who have an MRI (either 1.5T or 3T) or CT scan performed after onset of symptoms and prior to randomization with findings consistent with the diagnosis of dementia due to Alzheimer's disease and without any other clinically significant comorbid pathologies.
6. Subjects who have one (or more) identified adult study partner(s) who, in the opinion of the investigator, has sufficient contact with and knowledge about the subject as to be able to report knowledgeably about the subject's safety, compliance and adherence, cognition, function, and behavior.

Exclusion Criteria

1. Subjects who are female who are pregnant, nursing, or of childbearing potential and not practicing effective contraception.
2. Subjects who have signs of delirium.
3. Subjects who have had a cortical stroke within the preceding 2 years.
4. Subjects who have any diagnosis of dementia other than that related to Alzheimer's Disease, including concomitant vascular dementia.
5. Subjects who have a PET scan performed after onset of symptoms with negative amyloid results.
6. Subjects with a history of myocardial infarction, unstable angina, New York Heart Association (NYHA) class III or IV heart failure or stroke within the last 12 months.
7. Subjects with uncontrolled hypertension (systolic blood pressure \>160mm Hg or diastolic blood pressure \> 95mm Hg) or hypotension (systolic blood pressure \<90mm Hg or diastolic blood pressure \<50mm Hg).
8. Subjects who have clinically significant renal impairment (creatinine \> 1.5x ULN) or hepatic impairment (AST or ALT \> 2.5x ULN or total bilirubin \> 1.5x ULN).
9. Subjects who have history of cancer or malignant tumor within 5 years prior to screening with the exception of:

   1. Basal or squamous cell carcinoma of the skin or cervical dysplasia which has been adequately treated.
   2. In situ Grade 1 cervical cancer, fully treated at least 2 years prior to screening and without recurrence.
   3. Prostate cancer, confined to the prostate gland, which has been adequately treated (surgery and/or radiation) with normal or low and stable PSA levels for 2 years prior to screening.
10. Subjects who have history of untreated thyroid disorder or a seizure disorder.
11. Subjects who are being treated, or likely to require treatment during the study, with any medications prohibited by the study protocol.
12. Subjects who have participated in any investigational drug or device trial within the previous 30 days or five half-lives of the investigational drug at screening, whichever one is longer.
13. Subjects who have any other clinically significant abnormal result in laboratory tests such as abnormally low B12 or high TSH levels, as determined by the Investigator.
14. Subjects with any current psychiatric diagnosis other than AD if, in the judgment of the investigator, the psychiatric disorder or symptom is likely to confound interpretation of drug effect, affect cognitive assessments, or affect the subject's ability to complete the study.
15. Subjects whose treatment with FDA-approved AD medication (donepezil, galantamine, memantine, rivastigmine or their combinations) has not been stable for at least 3 months prior to screening. Treatment and dosing should remain stable, with no changes throughout the trial.
16. Subjects who are currently receiving (or unable to stop use for at least 21 days \[3 weeks\] prior to receiving the first dose of the AR1001 and throughout the study) prescription or non-prescription medications or other products known to be moderate or potent inhibitors/inducers of CYP3A4.
17. Subjects who have had any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first administration of the AR1001 and throughout the study.
18. Subjects, in the opinion of the Investigator, who are unsuitable to participate in the study.

Extension Phase Continuation Criterion

1. Subjects enrolled in AR1001-ADP2-US01 and completed 26 weeks of assigned dosing.

Primary outcomes:
measure: ADAS-Cog 13
timeFrame: 26 weeks
measure: ADCS-CGIC
timeFrame: 26 weeks
Secondary outcomes:
measure: MMSE-2
timeFrame: 26 weeks
measure: NPI
timeFrame: 26 weeks
measure: GDS
timeFrame: 26 weeks
measure: C-SSRS
timeFrame: 26 weeks
measure: QOL-AD
timeFrame: 26 weeks
measure: Treatment related adverse events
timeFrame: 26 weeks
Other outcomes:
Locations:
city: Banning
country: United States
facility: Advanced Clinical Research, Inc.
state: California
city: Sacramento
country: United States
facility: Northern California Research
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research
state: California
city: Lakeland
country: United States
facility: Meridien Research
state: Florida
city: Maitland
country: United States
facility: Meridien - Maitland
state: Florida
city: Miami
country: United States
facility: The Neurology Research Group
state: Florida
city: Orlando
country: United States
facility: Accelerated Enrollment Solutions (AES)
state: Florida
city: Palmetto Bay
country: United States
facility: IMIC, Inc
state: Florida
city: Saint Petersburg
country: United States
facility: Meridien Research - St Petersburg
state: Florida
city: Spring Hill
country: United States
facility: Meridien Research - Spring Hill
state: Florida
city: Tampa
country: United States
facility: Meridien Research - Tampa
state: Florida
city: Decatur
country: United States
facility: NeuroStudies, LLC
state: Georgia
city: Meridian
country: United States
facility: Advanced Clinical Research
state: Idaho
city: Las Vegas
country: United States
facility: Wake Research - CRCNV
state: Nevada
city: Beachwood
country: United States
facility: Rapid Medical Research
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Summerville
country: United States
facility: Palmetto Clinical Research
state: South Carolina
city: Cedar Park
country: United States
facility: Advanced Clinical Research - Cedar Park
state: Texas
city: Lampasas
country: United States
facility: FMC Science
state: Texas
city: West Jordan
country: United States
facility: Advanced Clinical Research, Inc.
state: Utah
city: Spokane
country: United States
facility: Kingfisher Cooperative, LLC
state: Washington
Study officials:
affiliation: SVP of global development
name: James Rock
role: STUDY_DIRECTOR
References: