Clinical trial NCT03462121: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mild to Moderate Dementia Due to Alzheimer's Disease
With or Without Coexisting Cerebrovascular Disease
Keywords: Alzheimer's Disease,
Dementia
Lead sponsor: Regenera Pharma Ltd
Sponsor class: INDUSTRY
First posted: 2018-03-12
Enrollment: 83
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change in (Alzheimer disease assessment scale) ADAS-Cog score between Baseline and Month 6
timeFrame: Month 6
measure: Change in CDR-SB score between Baseline and Month 6
timeFrame: Month 6
measure: AEs at Month 6
timeFrame: Month 6
measure: 12-lead ECG at Month 6
timeFrame: Month 6
measure: Clinical Laboratory Assessments - (blood and urine) at at Month 6
timeFrame: Month 6
measure: Vital Signs
timeFrame: Month 6
Secondary outcomes:
measure: Change from Baseline on ADAS-Cog total scores at Month 3
timeFrame: Months 3
measure: Change from Baseline on ADAS-Cog total scores at Month 5
timeFrame: Month 5
measure: Change from Baseline on ADAS-Cog total scores at Month 12
timeFrame: Month 12
measure: Change from Baseline on CDR-SB total scores at Month 3
timeFrame: Month 3
measure: Change from Baseline on CDR-SB total scores at Month 5
timeFrame: Month 5
measure: Change from Baseline on CDR-SB total scores at Month 12
timeFrame: Month 12
measure: Change from Baseline in ADCS-ADL total score at Month 3
timeFrame: Month 3
measure: Change from Baseline in ADCS-ADL total score at Months 12
timeFrame: Month 12
measure: Change from Baseline in NPI total score at Month 3
timeFrame: Month 3
measure: Change from Baseline in NPI total score at Month 6
timeFrame: Month 6
measure: Change from Baseline in NPI total score at Month 12
timeFrame: Month 12
measure: Change from Baseline in the MMSE at Month 3
timeFrame: Month 3
measure: Change from Baseline in the MMSE at Month 6
timeFrame: Month 6
measure: Change from Baseline in the MMSE at Month 12
timeFrame: Month 12
measure: AEs at Month 12
timeFrame: Month 12
measure: Clinically significant changes in vital signs at Month 12
timeFrame: Month 12
measure: 12-lead ECG at Month 12
timeFrame: Month 12
measure: Clinical Laboratory Assessments - (blood and urine) at Month 12
timeFrame: Month 12
measure: Vital Signs
timeFrame: Month 12
Other outcomes:
measure: AD blood biomarkers to assess change from Baseline at Month 6
timeFrame: Month 6
measure: AD blood biomarkers to assess change from Baseline at Month 12
timeFrame: Month 12
measure: Change in FDG-PET between Baseline and Month 6 in a subset of subjects (Optinal)
timeFrame: Month 6
Locations:
city: Peterborough
country: Canada
facility: Kawartha Centre - Redefining Healthy Aging
state: Ontario
city: Toronto
country: Canada
facility: Toronto Memory Program
state: Ontario
city: Toronto
country: Canada
facility: Gerontion Research Inc., The Center for Memory & Aging
state: Ontario
city: Gatineau
country: Canada
facility: Recherches Neuro-Hippocampe Inc. d/b/a Clinique de la Memoire de l'Outaouais
state: Quebec
city: Sherbrooke
country: Canada
facility: Diex Recherche Sherbrooke Inc.
state: Quebec
Study officials:
affiliation: Toronto Memory Program
name: Sharon Cohen, MD
role: PRINCIPAL_INVESTIGATOR
References: