Efficacy and Safety of AD-35 in Treatment of Subjects With Mild to Moderate Alzheimer's Disease

NCT03625401 | Unknown Phase 2 FDA Drug

• 1 other identifier: Hisun-AD-35-003
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 10

Brief Summary

multi-center, randomized, double-blind, parallel-group,placebo-controlled study to evaluate the safety and tolerability, efficacy, and PK of 60 mg AD-35 administered QD during 6 months of double-blind treatment followed by a second 6 months of open-label treatment to subjects with mild to moderate AD.

Conditions

Alzheimer Disease, Early Onset

Keywords

mild to moderate

Outcome Measures

Primary Outcomes (1)

• ADAS-cog 11 score

  The ADAS-cog 11 score is a 70-point scale administered by a clinician and is a standard measure to assess change in cognitive function in subjects with mild to moderate AD

  The primary efficacy endpoint will be change in the ADAS-cog 11 score from baseline to 6 months.

Secondary Outcomes (4)

• NPI score

  The secondary efficacy endpoint will be the change from baseline in the NPI score at 6 and 12 months

• ADCS-ADL score

  The secondary efficacy endpoint will be the change from baseline in the ADCS-ADL score at 6 and 12 months

• CIBIC+ score

  The secondary efficacy endpoint will be the change from baseline in the CIBIC+ score at 6 and 12 months

• ADAS-cog 11 score

  The secondary efficacy endpoint will be the change from baseline in ADAS-cog 11 score at 12 months

Study Arms (2)

AD-35 60 mg

EXPERIMENTAL

AD-35 60 mg group: 2 AD-35 30 mg tablets and 1 placebo tablet

Drug: AD-35 60mg group

Placebo of AD-35 30 mg

PLACEBO COMPARATOR

Placebo group: 3 placebo tablets

Drug: Placebo group

Interventions

AD-35 60mg group DRUG

AD-35 60mg QD

AD-35 60 mg

Placebo group DRUG

Placebo: 3 placebo of AD-35 30mg tablets

Placebo of AD-35 30 mg

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be diagnosed with probable AD in accordance with the National Institute on Aging and Alzheimer's Association (NIA-AA) (2011) criteria.
• Subjects must have a Mini-Mental State Examination (MMSE) score of ≥15 and ≤26 at screening and baseline.
• Subjects must have a brain magnetic resonance imaging (MRI) scan that is consistent with a clinical diagnosis of probable AD.
• Subjects should not have received Aβ-based or tau-based treatment for AD.
• Subjects who were previously treated with Acetyl cholinesterase inhibitor (AChEI) or memantine, must have been off of the therapy for at least 3 months prior to baseline assessments. Subjects who have been taking AChEI or memantine for ≤7 days may be considered for enrollment in this study.
• For subjects who are currently receiving other non-excluded prescription or over-the-counter medications that might affect cognitive function (eg, non-anticholinergic antidepressants, atypical antipsychotics, non-benzodiazepine anxiolytics, soporifics, centrally acting anticholinergic antihistamines, centrally acting anticholinergic antispasmodics):
• Treatment must be at a stable dose for ≥1 month prior to randomization and throughout the duration of the study.
• Treatment given intermittently and on a short-term basis must not be administered within 5 half-lives prior to the screening of neurocognitive assessments.
• Subjects must be male or female between 50 years to 85 years of age (inclusive), at screening.
• Female subjects must be post-menopausal for at least 2 consecutive years or surgically sterile (bilateral tubal ligation, hysterectomy, or bilateral oophorectomy) for at least 6 months prior to screening.
• Male subjects with partners of reproductive potential must agree to use a reliable means of contraception (eg, minimum condom + spermicide) during the study and 30 days after discontinuing the study drug.
• Subjects must have a reliable caregiver with contact at least 3 times per week (combination of face to face visits and telephone contact acceptable). The caregiver must be able to oversee the subject's compliance with study drug and participate in the subject's clinical assessment, to provide meaningful input into the NPI, ADCS-ADL, and CIBIC+.
• Subjects (or subject's legally authorized representatives and their caregivers) must be able to provide informed consent.
• Subjects (and their caregivers) must be able to read, write, speak, and understand English to ensure compliance with cognitive testing and study visit procedures.
• Subjects (and their caregivers) must be willing and able to comply with the protocol's requirements.

You may not qualify if:

• Lack of peripheral venous access.
• Uncorrected impairment of vision or hearing that would preclude the subject from taking tests, or subjects lacking the ability to communicate.
• Inability to tolerate MRI procedures or contraindication to MRI, including but not limited to MRI incompatible pacemakers; implantable cardioverter defibrillators; cochlear implants; cerebral aneurysm clips; implanted infusion pumps; implanted nerve stimulators; metallic splinters in the eye; other magnetic, electronic, or mechanical implants; or any other clinical history or examination finding that, in the judgment of the Investigator, would pose a potential hazard in combination with MRI.
• Severe or unstable medical condition that, in the opinion of the Investigator or Sponsor, would interfere with the subject's ability to complete the study assessments.
• History or presence of clinically evident vascular disease potentially affecting the brain (eg, stroke, clinically significant carotid or vertebral stenosis or plaque, aortic aneurysm, intracranial aneurysm, cerebral hemorrhage, arteriovenous malformation).
• History of severe, clinically significant (persistent neurologic deficit or structural brain damage) central nervous system trauma (eg, cerebral contusion).
• History or presence of intracranial tumor (eg, meningioma, glioma).
• Presence of infections that affect the brain function or history of infections that resulted in neurologic sequelae (eg, syphilis, neuroborreliosis, viral or bacterial meningitis/encephalitis,human immunodeficiency virus encephalopathy).
• History or presence of systemic autoimmune disorders potentially causing progressive neurologic disease (eg, multiple sclerosis, lupus erythematosus, anti-phospholipid antibody syndrome, Behçet disease).
• History or presence of psychiatric disease other than AD that may affect cognition or prevent completion of study procedures, including but not limited to clinically significant major psychiatric disorder according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) (eg, major depression, schizophrenia, bipolar disorder).
• A history of major depression is acceptable if no episode has been reported within the previous 5 years.
• History or presence of a neurologic disease other than AD that may affect cognition, including but not limited to Parkinson's disease, corticobasal degeneration, dementia with Lewy bodies, Creutzfeldt-Jakob disease, progressive supranuclear palsy, frontotemporal degeneration, Huntington's disease, normal pressure hydrocephalus, and hypoxia.
• History of seizures with the exception of childhood febrile seizures.
• Known or suspected history of alcohol or drug abuse within the previous 5 years (DSM-V criteria).
• Evidence of malignancies, acute infections, renal failure that requires dialysis, or other unstable medical disease not related to AD that in the Investigator's opinion would preclude subject participation.

Sponsors & Collaborators

• Zhejiang Hisun Pharmaceutical Co. Ltd.: lead
• Medpace, Inc.: collaborator

Study Sites (10)

Northern California Research

Sacramento, California, 95821, United States

Location

Pacific Research Network, Inc.

San Diego, California, 92103, United States

Location

Brain Matters Research

Delray Beach, Florida, 33445, United States

Location

Neuropsychiatric Research Center of Southwest Florida

Fort Myers, Florida, 33912, United States

Location

Meridien Research

Maitland, Florida, 32751, United States

Location

Meridien Research

Spring Hill, Florida, 34609, United States

Location

NeuroStudies

Decatur, Georgia, 30033, United States

Location

Alexian Brothers Neurosciences Institute

Elk Grove Village, Illinois, 60007, United States

Location

Advanced Memory Research Institute of NJ

Toms River, New Jersey, 08755, United States

Location

Clinilabs, Inc.

New York, New York, 10019, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Population Groups

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Demography; Population Characteristics

Study Officials

• Rentian (Roy) Feng, PhD

  Zhejiang Hisun Pharmaceuticals Co., Ltd

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: During the double-blind period, all of the study personnel, including Investigators, site personnel,the Sponsor's staff (eg, clinical research associate \[CRA\]/monitor), and study subjects will be blinded to treatment assignment. Placebo and AD-35 will be identical in appearance and packaging to preserve blinding.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: AD-35 60 mg group: 2 AD-35 30 mg tablets and 1 placebo tablet; Placebo group: 3 placebo tablets.

Study Record Dates

• First Submitted: July 24, 2018
• First Posted: August 10, 2018
• Study Start: October 4, 2018
• Primary Completion: December 1, 2020
• Study Completion: December 31, 2020
• Last Updated: March 25, 2020

Record last verified: 2020-03

Locations

US (10)