A Clinical Study Evaluating the Efficacy and Safety of RP... | NCT03462121

Status Module

Description Module

Label	Type	Description	Intervention Names
RPh201	Experimental	A 26-week schedule consisting of twice-weekly subcutaneous administration of 400 μL of the IMP (20 mg RPh201).	Drug: RPh201
Placebo	Placebo Comparator	A 26-week schedule consisting of twice-weekly subcutaneous administration of 400 μL of the vehicle control.	Other: Placebo

Name	Type	Description	Arm Group Labels	Other Names
RPh201	Drug	RPh201 is a well-defined extract from a botanical source	RPh201

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in (Alzheimer disease assessment scale) ADAS-Cog score between Baseline and Month 6	The ADAS-Cog is an established general cognitive measure scaled used in clinical trials of AD. The ADAS-Cog assesses multiple performance and cognitive domains including memory, language, praxis, and orientation. Test responses are scored using summed error points where 0 represents no errors and 70 represents errors on all items; higher scores indicate greater cognitive impairment.	Month 6
Change in CDR-SB score between Baseline and Month 6	The CDR is a global clinical scale with established diagnostic and severity-ranking utility widely used in clinical trials yielding global and sum of boxes scores (CDR-SB). The CDR global score is used in AD trials as a global measure of disease severity. The CDR is rated based on subject and informant input. The CDR assess three domains of cognition (memory, orientation, judgment/problem solving) and three domains of function (community affairs, home/hobbies, personal care) using semi- structured interviews of both the study subject and a companion/informant carried out by a trained rater and scored using a standard methodology. Each domain is rated on a 5-point scale of functioning as follows: (0) no impairment; (0.5) questionable impairment; (1) mild impairment; (2) moderate impairment; (3) severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). Higher scores indicate greater impairment.	Month 6
AEs at Month 6		Month 6
12-lead ECG at Month 6		Month 6
Clinical Laboratory Assessments - (blood and urine) at at Month 6	Chemistry: alkaline phosphatase, albumin, blood urea nitrogen, calcium, chloride, creatinine, glucose (random), inorganic phosphorus, potassium, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, lactate dehydrogenase, sodium, direct bilirubin, total bilirubin, total protein, amylase, uric acid Hematology: haemoglobin, hematocrit, red blood cell count, white blood cell (WBC) count, WBC differential (absolute counts), numerical platelet count Urinalysis: specific gravity, pH, ketones, glucose, nitrite, blood, leukocyte esterase, protein, urobilinogen, bilirubin If nitrite, blood, or protein tests are positive, a microscopic examination will be performed

Secondary Outcomes

Measure	Description	Time Frame
Change from Baseline on ADAS-Cog total scores at Month 3	The ADAS-Cog is an established general cognitive measure scaled used in clinical trials of AD. The ADAS-Cog assesses multiple performance and cognitive domains including memory, language, praxis, and orientation. Test responses are scored using summed error points where 0 represents no errors and 70 represents errors on all items; higher scores indicate greater cognitive impairment.

Other Outcomes

Measure	Description	Time Frame
AD blood biomarkers to assess change from Baseline at Month 6		Month 6
AD blood biomarkers to assess change from Baseline at Month 12		Month 12
Change in FDG-PET between Baseline and Month 6 in a subset of subjects (Optinal)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects must be ≥65 years of age at the time of consent.
Subjects 65-69 years old, inclusive, must have evidence of cerebrovascular disease.
Meet National Institute on Aging-Alzheimer's Association 2011 criteria for All-Cause Dementia and have evidence for probable AD or possible AD with coexisting cerebrovascular disease. Coexisting cerebrovascular disease includes evidence of any of the following: cortical infarcts, subcortical and lacunar infarcts, macro or micro-hemorrhage, and small vessel ischemic microangiopathy.
Willing and able to provide informed consent or, if incapable of informed consent, have a legally authorized representative willing to consent on their behalf.
MMSE at screen visit: 15-22, inclusive.
Cholinesterase inhibitors, memantine, and other background medications impacting cognition and mood, if used, are at stable doses for at least 6 weeks prior to screening.
A study partner is available who has adequate contact with the subject to administer study drug, oversee study drug compliance, report on adverse events (AEs), and provide meaningful input into scales and assessments.
Adequate hearing, vision, and fluency in the language of testing.
Magnetic resonance imaging (MRI) of the brain must reveal findings consistent with AD with or without coexisting cerebrovascular disease. In subjects for whom brain MRI is contraindicated (e.g., presence of a pacemaker), computed tomography (CT) of the brain is acceptable. Historic MRI or CT scans up to 18 months prior to screening may be used for inclusion unless there have been interval clinical events warranting an updated scan.
Male subjects who are sexually active must agree to use one of the following acceptable methods of birth control from Screening and for at least one month after the last dose of study drug: abstinence (no sexual intercourse), male condom, or vasectomy.
Subjects must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Optional FDG-PET sub-study: no contraindications to PET imaging. Individuals participating in the FDG-PET sub-study will be capped at 15 volunteers and a further cap may be imposed on the number enrolling in this sub-study without evidence of cerebrovascular disease.

Exclusion Criteria:

Neurological or non-neurological conditions other than AD and cerebrovascular disease that, in the Investigator's opinion, contribute to, or provide alternative etiology for, the subject's dementia. Examples include, but are not limited to, brain tumors, clinically significant head injury, Parkinson's disease, current or prior excess use of alcohol that, in the investigator's judgment, has caused or significantly contributed to the subject's cognitive decline, or primary psychiatric disorders (e.g., schizophrenia or bipolar affective disorder).
Unstable medical conditions which are likely to impact subject's ability to complete the trial and which are likely to confound AE assessment. These include, but are not limited to, uncontrolled hypertension, uncontrolled diabetes, and cancer within past the 2 years. Exceptions include prostate cancer in-situ and local basal and squamous cell skin cancers.
Chronic use of systemic or inhaled steroids (use of topical steroids is acceptable).
Other concomitant medications that, in the Investigator's judgment, impair cognition and/or confound efficacy assessments.
Women of child-bearing potential are excluded (e.g., women who have not been post-menopausal for at least 2 years or are not surgically sterile).
Treatment with investigational product from a previous clinical drug trial within the last 30 days or five half-lives prior to Visit 2 (Baseline), whichever is longer.

Facility	Status	City	State	ZIP	Country	Contacts
Kawartha Centre - Redefining Healthy Aging		Peterborough	Ontario	K9H 2P4	Canada
Toronto Memory Program

ID	Term
D000544	Alzheimer Disease
D003704	Dementia

ID	Term
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D024801	Tauopathies
D019636	Neurodegenerative Diseases
D019965	Neurocognitive Disorders
D001523	Mental Disorders

ID	Term
D004042	Dietary Fats, Unsaturated
D004041	Dietary Fats
D005223	Fats
D008055	Lipids
D005224	Fats, Unsaturated
D010938	Plant Oils
D009821	Oils
D028321	Plant Preparations
D001688	Biological Products
D045424	Complex Mixtures
D005502	Food
D000066888	Diet, Food, and Nutrition
D010829	Physiological Phenomena
D019602	Food and Beverages