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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03713957
Recruitment Status : Completed
First Posted : October 22, 2018
Results First Posted : May 9, 2022
Last Update Posted : May 9, 2022
Sponsor:
Collaborator:
Michael J. Fox Foundation for Parkinson's Research
Information provided by (Responsible Party):
Alkahest, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Parkinson Disease
Interventions Drug: GRF6021
Other: Placebo
Enrollment 79
Recruitment Details  
Pre-assignment Details  
Arm/Group Title GRF6021 Placebo
Hide Arm/Group Description

Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13.

GRF6021: GRF6021 for IV infusion

Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13.

Placebo: Placebo for IV infusion

Period Title: Overall Study
Started 53 26
Completed 35 16
Not Completed 18 10
Arm/Group Title GRF6021 Placebo Total
Hide Arm/Group Description

Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13.

GRF6021: GRF6021 for IV infusion

Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13.

Placebo: Placebo for IV infusion

Total of all reporting groups
Overall Number of Baseline Participants 53 26 79
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 53 participants 26 participants 79 participants
67.1  (7.63) 68.4  (8.88) 67.5  (8.03)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 53 participants 26 participants 79 participants
Female
16
  30.2%
10
  38.5%
26
  32.9%
Male
37
  69.8%
16
  61.5%
53
  67.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 53 participants 26 participants 79 participants
Hispanic or Latino
25
  47.2%
13
  50.0%
38
  48.1%
Not Hispanic or Latino
28
  52.8%
13
  50.0%
41
  51.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 53 participants 26 participants 79 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
9
  17.0%
2
   7.7%
11
  13.9%
White
44
  83.0%
24
  92.3%
68
  86.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 53 participants 26 participants 79 participants
United States
47
  88.7%
23
  88.5%
70
  88.6%
Australia
1
   1.9%
0
   0.0%
1
   1.3%
France
5
   9.4%
3
  11.5%
8
  10.1%
1.Primary Outcome
Title Incidence of Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Hide Description Treatment-emergent adverse events identified by MedDRA preferred term and grouped by MedDRA System Organ Class
Time Frame Approximately 24 Months
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set includes all subjects at least one dose of the study agent. All safety analyses were performed using the Safety Set, based on treatment received.
Arm/Group Title GRF6021 Placebo
Hide Arm/Group Description:

Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13.

GRF6021: GRF6021 for IV infusion

Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13.

Placebo: Placebo for IV infusion

Overall Number of Participants Analyzed 51 25
Measure Type: Number
Unit of Measure: participants
Participants with at least one TEAE 45 20
Participants with at least one SAE 5 0
2.Secondary Outcome
Title The Montreal Cognitive Assessment (MoCA) Score.
Hide Description 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)].
Time Frame Change from Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title GRF6021 Placebo
Hide Arm/Group Description:

Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13.

GRF6021: GRF6021 for IV infusion

Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13.

Placebo: Placebo for IV infusion

Overall Number of Participants Analyzed 44 22
Mean (Standard Deviation)
Unit of Measure: score on a scale
1.30  (3.62) 0.80  (3.13)
3.Secondary Outcome
Title 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.
Hide Description

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.

Time Frame Change from Baseline to Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
A subset of the Evaluable set comprised of subjects who receive all 10 planned doses, who complete Visit 18 and Visit 19 in window, and who do not have any of the deviations listed below or any other deviation that could potentially affect the assessment of efficacy identified prior to database lock.
Arm/Group Title GRF6021 Placebo
Hide Arm/Group Description:

Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13.

GRF6021: GRF6021 for IV infusion

Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13.

Placebo: Placebo for IV infusion

Overall Number of Participants Analyzed 35 16
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Continuity of Attention Number Analyzed 35 participants 16 participants
-0.42  (1.12) -0.28  (1.12)
Reaction Time Variability Number Analyzed 35 participants 16 participants
4.67  (8.40) 2.87  (8.40)
Quality of Working Memory Number Analyzed 34 participants 16 participants
0.09  (0.12) -0.04  (0.12)
Quality of Episodic Memory Number Analyzed 33 participants 16 participants
-10.02  (15.82) 8.65  (15.82)
4.Secondary Outcome
Title The Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency.
Hide Description 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.
Time Frame Change from Baseline to Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title GRF6021 Placebo
Hide Arm/Group Description:

Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13.

GRF6021: GRF6021 for IV infusion

Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13.

Placebo: Placebo for IV infusion

Overall Number of Participants Analyzed 40 20
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
5.00
(-3.12 to 13.13)
-1.59
(-11.77 to 8.58)
5.Secondary Outcome
Title The Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) 1, 2, 3, and Total Score.
Hide Description 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.
Time Frame Change from Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title GRF6021 Placebo
Hide Arm/Group Description:

Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13.

GRF6021: GRF6021 for IV infusion

Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13.

Placebo: Placebo for IV infusion

Overall Number of Participants Analyzed 44 22
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
-8.89
(-13.74 to -4.04)
-9.53
(-16.43 to -2.64)
6.Secondary Outcome
Title The Schwab and England Activities of Daily Living (SE-ADL) Scale.
Hide Description 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%.
Time Frame Change from Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The difference between the Number Analyzed at Baseline and week 24 timepoint is due the withdrawal of participants or missed assessments.
Arm/Group Title GRF6021 Placebo
Hide Arm/Group Description:

Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13.

GRF6021: GRF6021 for IV infusion

Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13.

Placebo: Placebo for IV infusion

Overall Number of Participants Analyzed 50 25
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline Number Analyzed 50 participants 25 participants
100% Independency
2
   4.0%
2
   8.0%
90% Independency
10
  20.0%
2
   8.0%
80% Independency
21
  42.0%
11
  44.0%
70% Independency
9
  18.0%
4
  16.0%
60% Independency
3
   6.0%
4
  16.0%
50% Independency
1
   2.0%
0
   0.0%
40% Independency
1
   2.0%
1
   4.0%
30% Independency
3
   6.0%
0
   0.0%
20% Independency
0
   0.0%
1
   4.0%
10% Independency
0
   0.0%
0
   0.0%
0% Independency
0
   0.0%
0
   0.0%
Week 24 Number Analyzed 43 participants 21 participants
100% Independency
2
   4.7%
1
   4.8%
90% Independency
10
  23.3%
4
  19.0%
80% Independency
15
  34.9%
7
  33.3%
70% Independency
6
  14.0%
4
  19.0%
60% Independency
4
   9.3%
2
   9.5%
50% Independency
3
   7.0%
1
   4.8%
40% Independency
1
   2.3%
0
   0.0%
30% Independency
1
   2.3%
1
   4.8%
20% Independency
0
   0.0%
1
   4.8%
10% Independency
1
   2.3%
0
   0.0%
0% Independency
0
   0.0%
0
   0.0%
7.Secondary Outcome
Title The Clinical Impression of Severity Index - PD (CISI-PD).
Hide Description 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.
Time Frame Change from Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title GRF6021 Placebo
Hide Arm/Group Description:

Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13.

GRF6021: GRF6021 for IV infusion

Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13.

Placebo: Placebo for IV infusion

Overall Number of Participants Analyzed 43 21
Least Squares Mean (95% Confidence Interval)
Unit of Measure: change from baseline score
-0.54
(-1.91 to 0.83)
-0.55
(-2.34 to 1.24)
8.Secondary Outcome
Title The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39).
Hide Description 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.
Time Frame Change from Baseline to Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title GRF6021 Placebo
Hide Arm/Group Description:

Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13.

GRF6021: GRF6021 for IV infusion

Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13.

Placebo: Placebo for IV infusion

Overall Number of Participants Analyzed 40 18
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
-4.88
(-11.46 to 1.69)
-6.29
(-14.81 to 2.23)
9.Secondary Outcome
Title The Geriatric Depression Scale-15 (GDS-15).
Hide Description 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.
Time Frame Change from Baseline to Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title GRF6021 Placebo
Hide Arm/Group Description:

Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13.

GRF6021: GRF6021 for IV infusion

Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13.

Placebo: Placebo for IV infusion

Overall Number of Participants Analyzed 41 20
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
0.30
(-1.30 to 1.89)
0.27
(-1.74 to 2.27)
10.Secondary Outcome
Title The Digital Clock Drawing Test (dCDT).
Hide Description 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.
Time Frame Change from Baseline to Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title GRF6021 Placebo
Hide Arm/Group Description:

Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13.

GRF6021: GRF6021 for IV infusion

Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13.

Placebo: Placebo for IV infusion

Overall Number of Participants Analyzed 36 20
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
9.25
(1.69 to 16.80)
1.58
(-7.61 to 10.77)
11.Secondary Outcome
Title 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.
Hide Description

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.

Time Frame Change from Baseline to Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
A subset of the Evaluable set comprised of subjects who receive all 10 planned doses, who complete Visit 18 and Visit 19 in window, and who do not have any of the deviations listed below or any other deviation that could potentially affect the assessment of efficacy identified prior to database lock.
Arm/Group Title GRF6021 Placebo
Hide Arm/Group Description:

Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13.

GRF6021: GRF6021 for IV infusion

Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13.

Placebo: Placebo for IV infusion

Overall Number of Participants Analyzed 35 16
Least Squares Mean (Standard Error)
Unit of Measure: ms
Power of Attention Number Analyzed 35 participants 16 participants
28.14  (90.89) 133.32  (90.89)
Cognitive Reaction Time Number Analyzed 35 participants 16 participants
-49.49  (75.69) 35.45  (75.69)
Speed of Memory Number Analyzed 33 participants 16 participants
46.97  (331.56) 232.33  (331.56)
Time Frame 24 Months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title GRF6021 Placebo
Hide Arm/Group Description

Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13.

GRF6021: GRF6021 for IV infusion

Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13.

Placebo: Placebo for IV infusion

All-Cause Mortality
GRF6021 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/51 (0.00%)      0/25 (0.00%)    
Hide Serious Adverse Events
GRF6021 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/51 (9.80%)      0/25 (0.00%)    
General disorders     
Gastritis   1/51 (1.96%)  1 0/25 (0.00%)  0
Injury, poisoning and procedural complications     
Road Traffic Accident   1/51 (1.96%)  1 0/25 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast Cancer   1/51 (1.96%)  1 0/25 (0.00%)  0
Psychiatric disorders     
Mental Changes   1/51 (1.96%)  1 0/25 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pulmonary Embolism   1/51 (1.96%)  1 0/25 (0.00%)  0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
GRF6021 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   45/51 (88.24%)      20/25 (80.00%)    
Gastrointestinal disorders     
Diarrhoea   3/51 (5.88%)  3 1/25 (4.00%)  1
General disorders     
Oedema peripheral   2/51 (3.92%)  2 2/25 (8.00%)  2
Infections and infestations     
Upper respiratory tract infection   4/51 (7.84%)  4 1/25 (4.00%)  1
Injury, poisoning and procedural complications     
Fall   7/51 (13.73%)  7 1/25 (4.00%)  1
Laceration   3/51 (5.88%)  3 1/25 (4.00%)  1
Investigations     
Blood pressure diastolic decreased   2/51 (3.92%)  2 4/25 (16.00%)  4
Musculoskeletal and connective tissue disorders     
Arthralgia   4/51 (7.84%)  4 0/25 (0.00%)  0
Back Pain   1/51 (1.96%)  1 3/25 (12.00%)  3
Nervous system disorders     
Headache   8/51 (15.69%)  8 2/25 (8.00%)  2
Dizziness   5/51 (9.80%)  5 1/25 (4.00%)  1
Vascular disorders     
Hypotension   6/51 (11.76%)  6 2/25 (8.00%)  2
Hypertension   2/51 (3.92%)  2 2/25 (8.00%)  2
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Clinical Trial Agreement contains language that restricts the PI from discussing or publishing Sponsor confidential and/or proprietary information. The embargo period may be extended by mutual agreement of the Sponsor and PI.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Head of Communications
Organization: Alkahest, Inc.
Phone: (650) 801-0474
EMail: info@alkahest.com
Layout table for additonal information
Responsible Party: Alkahest, Inc.
ClinicalTrials.gov Identifier: NCT03713957    
Other Study ID Numbers: Alkahest study 6021-201
First Submitted: October 18, 2018
First Posted: October 22, 2018
Results First Submitted: December 8, 2021
Results First Posted: May 9, 2022
Last Update Posted: May 9, 2022