A Study to Assess the Safety of GRF6021 Infusions in Subjects With Parkinson's Disease and Cognitive Impairment

Study Overview
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Brief Summary
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This study will evaluate the safety, tolerability, and potential effects on cognition of GRF6021, a plasma-derived product, administered as an intravenous (IV) infusion, to subjects with Parkinson's disease and cognitive impairment.

Detailed Description
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This is a randomized, double-blind, placebo-controlled study to assess the safety and tolerability of GRF6021, a plasma derived product, administered by intravenous (IV) infusion to subjects with Parkinson's disease (PD) and cognitive impairment. The study duration for the subjects will be approximately 7 months.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Tolerability of GRF6021 Infusions in Subjects With Parkinson's Disease and Cognitive Impairment

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: GRF6021
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Parkinson's Disease (PD), with at least 1 year of PD symptoms. Diagnosis of PD with mild cognitive impairment (PD-MCI) or probable or possible Parkinson's disease dementia according to Movement Disorder Society's Clinical Diagnostic criteria. Score on the Montreal Cognitive Assessment (MoCA) of 13-25. Modified Hoehn and Yahr Stages 1-4. Modified Hachinski Ischemic Scale (MHIS) score of 4 or less. Exclusion Criteria: History of blood coagulation disorders or hypercoagulability. Current use of anticoagulant therapy. Use of antiplatelet drugs (e.g., aspirin or clopidogrel) is acceptable. Prior hypersensitivity reaction to any human blood product or any IV infusion. Treatment with any human blood product, including transfusions and IV immunoglobulin, during the 6 months prior to screening. History of immunoglobulin A or haptoglobin deficiency; stroke, anaphylaxis, or thromboembolic complications of IV immunoglobulins. Heart disease, as evidenced by myocardial infarction, unstable, new onset or severe angina, or congestive heart failure in the 6 months prior to dosing Hemoglobin < 10 g/dL in women and < 11 g/dL in men.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GRF6021<br>Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13. | Drug: GRF6021<br>* GRF6021 for IV infusion<br>|
| Placebo Comparator: Placebo<br>Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13. | Other: Placebo<br>* Placebo for IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Treatment-emergent adverse events identified by MedDRA preferred term and grouped by MedDRA System Organ Class | Approximately 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Montreal Cognitive Assessment (MoCA) Score. | Change from baseline in the The Montreal Cognitive Assessment (MoCA). The MoCA is a 30-point test, which assess the attention and concentration, executive functions, memory, visuospatial abilities, language abilities, conceptual thinking, calculations, and orientation. Higher scores indicate better cognitive function; the total possible score is 30 and a score of 26 or more is considered normal. A positive value of change means an improvement, and a negative value of change means deterioration. Score range [0 (min) - 30 (Max)]. | Change from Baseline to Week 16 | 
| Continuity of Attention, Reaction Time Variability, Working Memory, and Episodic Memory on the Cognitive Drug Research Computerized Cognition Battery (CDR-CCB) as Assessed by Change From Baseline in CDR-CCB. | The CDR-CCB is an automated cognitive function assessment system. The secondary efficacy outcomes involved the following composite scores: Continuity of Attention: Min: - 20 # ; 35 # Reaction Time Variability: Min: 0 #; Max: 900 # Quality of Working Memory: Min : 0 # ; Max: 2 # Quality of Episodic Memory: Min: -400 #; Max: 400 # Note: # denotes no specific unit Lower scores reflect poorer ability for Continuity of Attention, Quality of Working Memory, and Quality of Episodic Memory; thus, a negative change from baseline reflects impairment compared to baseline. Whereas, for Reaction Time Variability, higher scores reflect poorer ability, and a positive change from baseline reflects impairment compared to baseline. | Change from Baseline to Week 20 | 
| The Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency. | Change from baseline in the Delis-Kaplan Executive Function System (D-KEFS). The D-KEFS Verbal Fluency test is used for assessment of executive function and has three conditions: Letter Fluency, Category Fluency, and Category Switching. Higher scores indicate more correct responses. A positive value of change means an improvement and a negative value of change means deterioration. The minimum score is 0 and there is no concrete maximum score. | Change from Baseline to Week 20 | 
| The Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) 1, 2, 3, and Total Score. | Change from baseline in the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS). The MDS-UPDRS contains 4 subscales: Part 1, Mentation, Behavior, and Mood; Part 2, Activities of Daily Living; Part 3, Motor; Part 4, Complications nonmotor experiences of daily living (13 items), motor experiences of daily living (13 items), motor examination (18 items), and motor complications (six items). The rating for each item is from 0 (normal) to 4 (severe). The total score for each Part is obtained from the sum of the corresponding item scores. For this study, Parts 1-3 will be completed. Part 1 score ranges from 0 to 52. Part 2 score ranges from 0 to 52. Part 3 score ranges from 0 to 132. Total score possible is 0 to 236. | Change from Baseline to Week 16 | 
| The Schwab and England Activities of Daily Living (SE-ADL) Scale. | Change from baseline in the Schwab and England Activities of Daily Living (SE-ADL). The SE-ADL evaluates patients' perceptions of global functional capacity and dependence. Scoring is expressed in terms of percentage, in 10 steps from 100 to 0 (100%, normal status; 0%, bedridden with vegetative dysfunction), so that the lower the score, the worse the functional status. The range is 0% to 100%. | Change from Baseline to Week 24 | 
| The Clinical Impression of Severity Index - PD (CISI-PD). | Change from baseline in The Clinical Impression of Severity Index PD (CISI-PD). The CISI-PD is a severity index formed by four items (motor signs, disability, motor complications, and cognitive status), rated 0 (not at all) to 6 (very severe or completely disabled); the possible scores range from 0 to 24. A total score is calculated by summing the item scores. Higher scores indicate worse severity. A negative value of change means an improvement and a positive value of change means deterioration. | Change from Baseline to Week 24 | 
| The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39). | Change from baseline in the Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39). The PDQ-39 is a self-administered questionnaire of 39 questions relating to 8 key areas of health and daily activities, including both motor and non-motor symptoms. It is scored on a scale of 0 -100 with lower scores indicating better health and high scores indicating more severe symptoms. | Change from Baseline to Week 20 | 
| The Geriatric Depression Scale-15 (GDS-15). | Change from baseline in the Geriatric Depression Scale (GDS-15). The GDS-15 is a 15-item yes/no questionnaire of depression in older adults. Each depressive answer is 1 point. The final score is the tally of the number of depressive answers with the following scores indicating depression: 0-4 No depression; 5-10 Suggestive of a mild depression; 11 + Suggestive of severe depression. The possible scores range from 0 - 15. | Change from Baseline to Week 20 | 
| The Digital Clock Drawing Test (dCDT). | Change from baseline in the digital clock drawing test (dCDT). The pen-like dCDT device will be used to gather the x-y coordinates that describe the movement of the stylus as it changes its position during the assessment. It also assesses when the stylus or writing device is not exerting pressure on the writing surface. The dCDT score is a number from 0 and 100 that represents a person's overall cognitive function as assessed by DCT clock. The total possible score is 100. A negative value of change means a deterioration and a positive value of change means an improvement. | Change from Baseline to Week 20 | 
| Power of Attention, Cognitive Reaction Time, and Speed of Memory on the Cognitive Drug Research Computerized Cognition Battery (CDR-CCB) as Assessed by Change From Baseline in CDR-CCB. | The CDR-CCB is an automated cognitive function assessment system. The secondary efficacy outcomes involved the following composite scores: Power of Attention: Min: 350 ms ; Max: 60000 ms Cognitive Reaction Time: Min: - 30000 ms; Max : 30000 ms Speed of Memory: Min 800 ms; Max: 120000 ms Higher scores reflect poorer ability, and a positive change from baseline reflects impairment compared to baseline. | Change from Baseline to Week 20 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Neurodegenerative Diseases, Neurocognitive Disorders, Mental Disorders, Parkinson's Disease, Dementia