Back to resultsA Clinical Study Evaluating the Efficacy and Safety of RPh201 Treatment in Individuals With Alzheimer's Disease With or Without Coexisting Cerebrovascular Disease
Primary Purpose
Mild to Moderate Dementia Due to Alzheimer's Disease, With or Without Coexisting Cerebrovascular Disease
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
RPh201
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Mild to Moderate Dementia Due to Alzheimer's Disease focused on measuring Alzheimer's Disease,, Dementia
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.
Sites / Locations
- Kawartha Centre - Redefining Healthy Aging
- Toronto Memory Program
- Gerontion Research Inc., The Center for Memory & Aging
- Recherches Neuro-Hippocampe Inc. d/b/a Clinique de la Memoire de l'Outaouais
- Diex Recherche Sherbrooke Inc.
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
RPh201
Placebo
Arm Description
A 26-week schedule consisting of twice-weekly subcutaneous administration of 400 μL of the IMP (20 mg RPh201).
A 26-week schedule consisting of twice-weekly subcutaneous administration of 400 μL of the vehicle control.
Outcomes
Primary Outcome Measures
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.
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.
AEs at Month 6
12-lead ECG at 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
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.
Secondary Outcome Measures
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.
Change from Baseline on ADAS-Cog total scores at Month 5
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.
Change from Baseline on ADAS-Cog total scores at Month 12
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.
Change from Baseline on CDR-SB total scores at Month 3
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.
Change from Baseline on CDR-SB total scores at Month 5
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.
Change from Baseline on CDR-SB total scores at Month 12
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.
Change from Baseline in ADCS-ADL total score at Month 3
The ADCS-ADL is an assessment consisting of 23 basic and instrumental ADLs used in mild to moderate AD subjects.7 The scores of the informant-rated assessment are graded against a 78- point scale, with lower scores indicating greater impairment.
Change from Baseline in ADCS-ADL total score at Months 12
The ADCS-ADL is an assessment consisting of 23 basic and instrumental ADLs used in mild to moderate AD subjects.7 The scores of the informant-rated assessment are graded against a 78- point scale, with lower scores indicating greater impairment.
Change from Baseline in NPI total score at Month 3
The NPI is designed to detect, quantify, and track changes of psychiatric symptoms in a demented population.6 It uses a structured, caregiver-based interview format to assess 10 behavioral domains (delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, apathy, irritability, euphoria, disinhibition, and aberrant motor behavior). The same behaviors are then rated on level of severity (1 = mild, 2 = moderate, 3 = severe). The domain total score is the product of the frequency score multiplied by the severity score for that behavioral domain. An NPI total score is obtained by summing all the individual domain total scores.
Change from Baseline in NPI total score at Month 6
The NPI (Appendix 7) is designed to detect, quantify, and track changes of psychiatric symptoms in a demented population.6 It uses a structured, caregiver-based interview format to assess 10 behavioral domains (delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, apathy, irritability, euphoria, disinhibition, and aberrant motor behavior). The same behaviors are then rated on level of severity (1 = mild, 2 = moderate, 3 = severe). The domain total score is the product of the frequency score multiplied by the severity score for that behavioral domain. An NPI total score is obtained by summing all the individual domain total scores.
Change from Baseline in NPI total score at Month 12
The NPI (Appendix 7) is designed to detect, quantify, and track changes of psychiatric symptoms in a demented population.6 It uses a structured, caregiver-based interview format to assess 10 behavioral domains (delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, apathy, irritability, euphoria, disinhibition, and aberrant motor behavior). The same behaviors are then rated on level of severity (1 = mild, 2 = moderate, 3 = severe). The domain total score is the product of the frequency score multiplied by the severity score for that behavioral domain. An NPI total score is obtained by summing all the individual domain total scores.
Change from Baseline in the MMSE at Month 3
The MMSE is a brief 30-point examination consisting of 11 questions intended to evaluate an adult subject's level of cognition. The MMSE evaluates 6 areas of cognition: orientation, attention, immediate recall, short-term recall, language, and the ability to follow simple verbal and written commands. In addition, it provides a total score allowing the examiner to evaluate the severity of cognitive impairment.
The MMSE will be scored using backward spelling (WORLD) and not serial subtractions. The scoring of WORLD will follow the original Folstein et al (1975)8 instructions for this assessment.
Change from Baseline in the MMSE at Month 6
The MMSE is a brief 30-point examination consisting of 11 questions intended to evaluate an adult subject's level of cognition. The MMSE evaluates 6 areas of cognition: orientation, attention, immediate recall, short-term recall, language, and the ability to follow simple verbal and written commands. In addition, it provides a total score allowing the examiner to evaluate the severity of cognitive impairment.
The MMSE will be scored using backward spelling (WORLD) and not serial subtractions. The scoring of WORLD will follow the original Folstein et al (1975)8 instructions for this assessment.
Change from Baseline in the MMSE at Month 12
The MMSE is a brief 30-point examination consisting of 11 questions intended to evaluate an adult subject's level of cognition. The MMSE evaluates 6 areas of cognition: orientation, attention, immediate recall, short-term recall, language, and the ability to follow simple verbal and written commands. In addition, it provides a total score allowing the examiner to evaluate the severity of cognitive impairment.
The MMSE will be scored using backward spelling (WORLD) and not serial subtractions. The scoring of WORLD will follow the original Folstein et al (1975)8 instructions for this assessment.
AEs at Month 12
Clinically significant changes in vital signs at Month 12
12-lead ECG at Month 12
Clinical Laboratory Assessments - (blood and urine) at Month 12
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03462121
Brief Title
A Clinical Study Evaluating the Efficacy and Safety of RPh201 Treatment in Individuals With Alzheimer's Disease With or Without Coexisting Cerebrovascular Disease
Official Title
A 6-Month, Double-Blind, Phase 2 Study and 6-Month Open- Label Extension Evaluating the Safety, Tolerability, and Clinical Benefit of RPh201 in Individuals With Alzheimer's Disease With or Without Coexisting Cerebrovascular Disease
Study Type
Interventional
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
March 1, 2018 (Actual)
Primary Completion Date
December 28, 2019 (Actual)
Study Completion Date
March 30, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regenera Pharma Ltd
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mild to Moderate Dementia Due to Alzheimer's Disease, With or Without Coexisting Cerebrovascular Disease
Keywords
Alzheimer's Disease,, Dementia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
1:2
Allocation
Randomized
Enrollment
83 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RPh201
Arm Type
Experimental
Arm Description
A 26-week schedule consisting of twice-weekly subcutaneous administration of 400 μL of the IMP (20 mg RPh201).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
A 26-week schedule consisting of twice-weekly subcutaneous administration of 400 μL of the vehicle control.
Intervention Type
Drug
Intervention Name(s)
RPh201
Intervention Description
RPh201 is a well-defined extract from a botanical source
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
Cottonseed oil
Intervention Description
Inactive placebo consisting of the therapeutic vehicle
Primary Outcome Measure Information:
Title
Change in (Alzheimer disease assessment scale) ADAS-Cog score between Baseline and Month 6
Description
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.
Time Frame
Month 6
Title
Change in CDR-SB score between Baseline and Month 6
Description
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.
Time Frame
Month 6
Title
AEs at Month 6
Time Frame
Month 6
Title
12-lead ECG at Month 6
Time Frame
Month 6
Title
Clinical Laboratory Assessments - (blood and urine) at at Month 6
Description
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
Time Frame
Month 6
Title
Vital Signs
Description
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.
Time Frame
Month 6
Secondary Outcome Measure Information:
Title
Change from Baseline on ADAS-Cog total scores at Month 3
Description
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.
Time Frame
Months 3
Title
Change from Baseline on ADAS-Cog total scores at Month 5
Description
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.
Time Frame
Month 5
Title
Change from Baseline on ADAS-Cog total scores at Month 12
Description
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.
Time Frame
Month 12
Title
Change from Baseline on CDR-SB total scores at Month 3
Description
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.
Time Frame
Month 3
Title
Change from Baseline on CDR-SB total scores at Month 5
Description
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.
Time Frame
Month 5
Title
Change from Baseline on CDR-SB total scores at Month 12
Description
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.
Time Frame
Month 12
Title
Change from Baseline in ADCS-ADL total score at Month 3
Description
The ADCS-ADL is an assessment consisting of 23 basic and instrumental ADLs used in mild to moderate AD subjects.7 The scores of the informant-rated assessment are graded against a 78- point scale, with lower scores indicating greater impairment.
Time Frame
Month 3
Title
Change from Baseline in ADCS-ADL total score at Months 12
Description
The ADCS-ADL is an assessment consisting of 23 basic and instrumental ADLs used in mild to moderate AD subjects.7 The scores of the informant-rated assessment are graded against a 78- point scale, with lower scores indicating greater impairment.
Time Frame
Month 12
Title
Change from Baseline in NPI total score at Month 3
Description
The NPI is designed to detect, quantify, and track changes of psychiatric symptoms in a demented population.6 It uses a structured, caregiver-based interview format to assess 10 behavioral domains (delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, apathy, irritability, euphoria, disinhibition, and aberrant motor behavior). The same behaviors are then rated on level of severity (1 = mild, 2 = moderate, 3 = severe). The domain total score is the product of the frequency score multiplied by the severity score for that behavioral domain. An NPI total score is obtained by summing all the individual domain total scores.
Time Frame
Month 3
Title
Change from Baseline in NPI total score at Month 6
Description
The NPI (Appendix 7) is designed to detect, quantify, and track changes of psychiatric symptoms in a demented population.6 It uses a structured, caregiver-based interview format to assess 10 behavioral domains (delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, apathy, irritability, euphoria, disinhibition, and aberrant motor behavior). The same behaviors are then rated on level of severity (1 = mild, 2 = moderate, 3 = severe). The domain total score is the product of the frequency score multiplied by the severity score for that behavioral domain. An NPI total score is obtained by summing all the individual domain total scores.
Time Frame
Month 6
Title
Change from Baseline in NPI total score at Month 12
Description
The NPI (Appendix 7) is designed to detect, quantify, and track changes of psychiatric symptoms in a demented population.6 It uses a structured, caregiver-based interview format to assess 10 behavioral domains (delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, apathy, irritability, euphoria, disinhibition, and aberrant motor behavior). The same behaviors are then rated on level of severity (1 = mild, 2 = moderate, 3 = severe). The domain total score is the product of the frequency score multiplied by the severity score for that behavioral domain. An NPI total score is obtained by summing all the individual domain total scores.
Time Frame
Month 12
Title
Change from Baseline in the MMSE at Month 3
Description
The MMSE is a brief 30-point examination consisting of 11 questions intended to evaluate an adult subject's level of cognition. The MMSE evaluates 6 areas of cognition: orientation, attention, immediate recall, short-term recall, language, and the ability to follow simple verbal and written commands. In addition, it provides a total score allowing the examiner to evaluate the severity of cognitive impairment.
The MMSE will be scored using backward spelling (WORLD) and not serial subtractions. The scoring of WORLD will follow the original Folstein et al (1975)8 instructions for this assessment.
Time Frame
Month 3
Title
Change from Baseline in the MMSE at Month 6
Description
The MMSE is a brief 30-point examination consisting of 11 questions intended to evaluate an adult subject's level of cognition. The MMSE evaluates 6 areas of cognition: orientation, attention, immediate recall, short-term recall, language, and the ability to follow simple verbal and written commands. In addition, it provides a total score allowing the examiner to evaluate the severity of cognitive impairment.
The MMSE will be scored using backward spelling (WORLD) and not serial subtractions. The scoring of WORLD will follow the original Folstein et al (1975)8 instructions for this assessment.
Time Frame
Month 6
Title
Change from Baseline in the MMSE at Month 12
Description
The MMSE is a brief 30-point examination consisting of 11 questions intended to evaluate an adult subject's level of cognition. The MMSE evaluates 6 areas of cognition: orientation, attention, immediate recall, short-term recall, language, and the ability to follow simple verbal and written commands. In addition, it provides a total score allowing the examiner to evaluate the severity of cognitive impairment.
The MMSE will be scored using backward spelling (WORLD) and not serial subtractions. The scoring of WORLD will follow the original Folstein et al (1975)8 instructions for this assessment.
Time Frame
Month 12
Title
AEs at Month 12
Time Frame
Month 12
Title
Clinically significant changes in vital signs at Month 12
Time Frame
Month 12
Title
12-lead ECG at Month 12
Time Frame
Month 12
Title
Clinical Laboratory Assessments - (blood and urine) at Month 12
Description
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
Time Frame
Month 12
Title
Vital Signs
Description
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.
Time Frame
Month 12
Other Pre-specified Outcome Measures:
Title
AD blood biomarkers to assess change from Baseline at Month 6
Time Frame
Month 6
Title
AD blood biomarkers to assess change from Baseline at Month 12
Time Frame
Month 12
Title
Change in FDG-PET between Baseline and Month 6 in a subset of subjects (Optinal)
Description
18-Fluoro-deoxyglucose positron emission tomography (FDG-PET) is a noninvasive, 3-dimensional imaging modality that has become widely used in the management of subjects with malignant lymphomas.9 Up to 15 subjects will participate in an optional FDG-PET sub-study to assess the effect of RPh201 on cerebral glucose metabolism at Baseline and after 6 months of treatment.
Time Frame
Month 6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sharon Cohen, MD
Organizational Affiliation
Toronto Memory Program
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kawartha Centre - Redefining Healthy Aging
City
Peterborough
State/Province
Ontario
ZIP/Postal Code
K9H 2P4
Country
Canada
Facility Name
Toronto Memory Program
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M3B 2S7
Country
Canada
Facility Name
Gerontion Research Inc., The Center for Memory & Aging
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4G 3E8
Country
Canada
Facility Name
Recherches Neuro-Hippocampe Inc. d/b/a Clinique de la Memoire de l'Outaouais
City
Gatineau
State/Province
Quebec
ZIP/Postal Code
J8T 8J1
Country
Canada
Facility Name
Diex Recherche Sherbrooke Inc.
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1L 0H8
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
A Clinical Study Evaluating the Efficacy and Safety of RPh201 Treatment in Individuals With Alzheimer's Disease With or Without Coexisting Cerebrovascular Disease
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