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

Parkinson Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03713957
• Other study ID #: Alkahest study 6021-201
• Status: Completed
• Phase: Phase 2
• Start date: November 12, 2018
• Est. completion date: July 20, 2020

Study information

• Verified date: May 2022
• Source: Alkahest, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: July 20, 2020
• Est. primary completion date: July 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Parkinson Disease

Intervention

Drug:
• GRF6021
GRF6021 for IV infusion

Other:
• Placebo
Placebo for IV infusion

Locations

Country	Name	City	State
Australia	Alfred Hospital	Melbourne	Victoria
France	Hopital Neurologique	Bron
France	Hopital Henri Mondor	Creteil
France	CHU Grenoble Alpes	Grenoble
France	Hopital Roger Salengro	Lille
France	Hopital de la Timone	Marseille
France	CHU Caremeau	Nimes
France	CHU de Poitiers	Poitiers
France	CHU Charles Nicolle	Rouen
France	CHU Purpan - Hopital Pierre Paul Riquet	Toulouse
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	NeuroTrials Research Inc.	Atlanta	Georgia
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Cleveland Clinic	Cleveland	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Moonshine Research Center	Doral	Florida
United States	Riverside Clinical Research	Edgewater	Florida
United States	Rocky Mountain Movement Disorders Center	Englewood	Colorado
United States	Quest Research Institute	Farmington Hills	Michigan
United States	MD Clinical	Hallandale Beach	Florida
United States	Research Centers of America, LLC	Hollywood	Florida
United States	Centex Studies, INC.	Houston	Texas
United States	Clinical Trials, Inc.	Little Rock	Arkansas
United States	Suncoast Research Group, LLC	Miami	Florida
United States	SRI Biosciences	Plymouth	Michigan
United States	Oregon Health & Science University	Portland	Oregon
United States	Wake Research	Raleigh	North Carolina
United States	PsychCare Consultants Research	Saint Louis	Missouri
United States	Qps_Mra, Llc	South Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Alkahest, Inc.	Michael J. Fox Foundation for Parkinson's Research

Countries where clinical trial is conducted

United States,  Australia,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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