A Clinical Study Evaluating the Efficacy and Safety of RPh201 Treatment in Individuals With Alzheimer's Disease With or Without Coexisting Cerebrovascular Disease

NCT03462121 | Completed Phase 2

• 1 other identifier: RGN-ADC-002
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 5

Brief Summary

This study is a randomized, double-blind, placebo-controlled, multicentre, Phase 2 study, with an optional open-label extension, to evaluate the safety, tolerability, and efficacy of RPh201 in subjects with mild to moderate AD who are eligible for enrollment in this study. Subject participation will include a Screening Phase, Treatment Phase, and an Optional Open-Label Extension. The Screening Phase will be up to 4 weeks prior to randomization. Both the subject and their study partner(s) will sign an informed consent form (ICF). At Visit 2, Subjects will be randomized 2:1 to RPh201 or placebo. The Treatment Phase will last for 6 months post-randomization, or until subject withdrawal from the study, whichever comes first. The Optional Open-Label Extension will begin once a subject has completed the Treatment Phase and the subject and their study partner(s) have signed an ICF to continue on the study. The Optional Open-Label Extension will continue for 6 months, or until subject withdrawal from the study, whichever comes first. Subjects who do not participate in the Optional Open-Label Extension will be asked to return for an optional post-study visit 6 months after the end of the Treatment Phase. Subjects may participate in an optional biomarker sub-study. Up to 15 subjects may also participate in an optional FDG-PET sub-study during their study participation. Separate informed consent will be required for both of these sub-studies.

Conditions

Mild to Moderate Dementia Due to Alzheimer's Disease; With or Without Coexisting Cerebrovascular Disease

Keywords

Alzheimer's Disease,; Dementia

Outcome Measures

Primary Outcomes (6)

• 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

  Month 6

• Vital Signs

  Vital signs consist of tympanic temperature, respiratory rate, blood pressure (systolic and diastolic blood pressure, mmHg), and pulse (bpm) after at least 3 minutes rest. Blood pressure will be measured in a sitting or semi-reclined seated position. Weight and height will be captured at Screening and weight will be captured at all other visits where this assessment is performed.

  Month 6

Secondary Outcomes (19)

• Change from Baseline on ADAS-Cog total scores at Month 3

  Months 3

• Change from Baseline on ADAS-Cog total scores at Month 5

  Month 5

• Change from Baseline on ADAS-Cog total scores at Month 12

  Month 12

• Change from Baseline on CDR-SB total scores at Month 3

  Month 3

• Change from Baseline on CDR-SB total scores at Month 5

  Month 5

Other Outcomes (3)

• 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)

  Month 6

Study Arms (2)

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

Interventions

RPh201 DRUG

RPh201 is a well-defined extract from a botanical source

RPh201

Placebo OTHER

Inactive placebo consisting of the therapeutic vehicle

Also known as: Cottonseed oil

Placebo

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Regenera Pharma Ltd: lead

Study Sites (5)

Kawartha Centre - Redefining Healthy Aging

Peterborough, Ontario, K9H 2P4, Canada

Location

Toronto Memory Program

Toronto, Ontario, M3B 2S7, Canada

Location

Gerontion Research Inc., The Center for Memory & Aging

Toronto, Ontario, M4G 3E8, Canada

Location

Recherches Neuro-Hippocampe Inc. d/b/a Clinique de la Memoire de l'Outaouais

Gatineau, Quebec, J8T 8J1, Canada

Location

Diex Recherche Sherbrooke Inc.

Sherbrooke, Quebec, J1L 0H8, Canada

Location

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Interventions

Cottonseed Oil

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fats, Unsaturated; Plant Oils; Oils; Plant Preparations; Biological Products; Complex Mixtures; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Sharon Cohen, MD

  Toronto Memory Program

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 1:2
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2018
• First Posted: March 12, 2018
• Study Start: March 1, 2018
• Primary Completion: December 28, 2019
• Study Completion: March 30, 2020
• Last Updated: April 30, 2020

Record last verified: 2019-06

Locations

CA (5)