Trial Outcomes & Findings for A Study to Assess the Safety of GRF6021 Infusions in Subjects With Parkinson's Disease and Cognitive Impairment (NCT NCT03713957)

NCT ID: NCT03713957

Last Updated: 2022-05-09

Results Overview

Treatment-emergent adverse events identified by MedDRA preferred term and grouped by MedDRA System Organ Class

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

79 participants

Primary outcome timeframe

Approximately 24 Months

Results posted on

2022-05-09

Participant Flow

Participant milestones

Participant milestones
Measure	GRF6021 Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13. GRF6021: GRF6021 for IV infusion	Placebo Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13. Placebo: Placebo for IV infusion
Overall Study STARTED	53	26
Overall Study COMPLETED	35	16
Overall Study NOT COMPLETED	18	10

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GRF6021 n=53 Participants Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13. GRF6021: GRF6021 for IV infusion	Placebo n=26 Participants Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13. Placebo: Placebo for IV infusion	Total n=79 Participants Total of all reporting groups
Age, Continuous	67.1 years STANDARD_DEVIATION 7.63 • n=5 Participants	68.4 years STANDARD_DEVIATION 8.88 • n=7 Participants	67.5 years STANDARD_DEVIATION 8.03 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	10 Participants n=7 Participants	26 Participants n=5 Participants
Sex: Female, Male Male	37 Participants n=5 Participants	16 Participants n=7 Participants	53 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	25 Participants n=5 Participants	13 Participants n=7 Participants	38 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants n=5 Participants	13 Participants n=7 Participants	41 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	2 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) White	44 Participants n=5 Participants	24 Participants n=7 Participants	68 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	47 Participants n=5 Participants	23 Participants n=7 Participants	70 Participants n=5 Participants
Region of Enrollment Australia	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment France	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: Approximately 24 Months

Population: 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.

Treatment-emergent adverse events identified by MedDRA preferred term and grouped by MedDRA System Organ Class

Outcome measures

Outcome measures
Measure	GRF6021 n=51 Participants Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13. GRF6021: GRF6021 for IV infusion	Placebo n=25 Participants Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13. Placebo: Placebo for IV infusion
Incidence of Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Participants with at least one TEAE	45 participants	20 participants
Incidence of Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Participants with at least one SAE	5 participants	0 participants

SECONDARY outcome

Timeframe: Change from Baseline to Week 16

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 \[0 (min) - 30 (Max)\].

Outcome measures

Outcome measures
Measure	GRF6021 n=44 Participants Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13. GRF6021: GRF6021 for IV infusion	Placebo n=22 Participants Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13. Placebo: Placebo for IV infusion
The Montreal Cognitive Assessment (MoCA) Score.	1.30 score on a scale Standard Deviation 3.62	0.80 score on a scale Standard Deviation 3.13

SECONDARY outcome

Timeframe: Change from Baseline to Week 20

Population: 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.

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.

Outcome measures

Outcome measures
Measure	GRF6021 n=35 Participants Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13. GRF6021: GRF6021 for IV infusion	Placebo n=16 Participants Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13. Placebo: Placebo for IV infusion
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. Continuity of Attention	-0.42 score on a scale Standard Error 1.12	-0.28 score on a scale Standard Error 1.12
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. Reaction Time Variability	4.67 score on a scale Standard Error 8.40	2.87 score on a scale Standard Error 8.40
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. Quality of Working Memory	0.09 score on a scale Standard Error 0.12	-0.04 score on a scale Standard Error 0.12
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. Quality of Episodic Memory	-10.02 score on a scale Standard Error 15.82	8.65 score on a scale Standard Error 15.82

SECONDARY outcome

Timeframe: Change from Baseline to Week 20

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.

Outcome measures

Outcome measures
Measure	GRF6021 n=40 Participants Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13. GRF6021: GRF6021 for IV infusion	Placebo n=20 Participants Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13. Placebo: Placebo for IV infusion
The Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency.	5.00 score on a scale Interval -3.12 to 13.13	-1.59 score on a scale Interval -11.77 to 8.58

SECONDARY outcome

Timeframe: Change from Baseline to Week 16

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.

Outcome measures

Outcome measures
Measure	GRF6021 n=44 Participants Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13. GRF6021: GRF6021 for IV infusion	Placebo n=22 Participants Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13. Placebo: Placebo for IV infusion
The Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) 1, 2, 3, and Total Score.	-8.89 score on a scale Interval -13.74 to -4.04	-9.53 score on a scale Interval -16.43 to -2.64

SECONDARY outcome

Timeframe: Change from Baseline to Week 24

Population: The difference between the Number Analyzed at Baseline and week 24 timepoint is due the withdrawal of participants or missed assessments.

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%.

Outcome measures

Outcome measures
Measure	GRF6021 n=50 Participants Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13. GRF6021: GRF6021 for IV infusion	Placebo n=25 Participants Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13. Placebo: Placebo for IV infusion
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Baseline · 100% Independency	2 Participants	2 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Baseline · 90% Independency	10 Participants	2 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Baseline · 80% Independency	21 Participants	11 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Baseline · 70% Independency	9 Participants	4 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Baseline · 60% Independency	3 Participants	4 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Baseline · 50% Independency	1 Participants	0 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Baseline · 40% Independency	1 Participants	1 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Baseline · 30% Independency	3 Participants	0 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Baseline · 20% Independency	0 Participants	1 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Baseline · 10% Independency	0 Participants	0 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Baseline · 0% Independency	0 Participants	0 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Week 24 · 100% Independency	2 Participants	1 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Week 24 · 90% Independency	10 Participants	4 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Week 24 · 80% Independency	15 Participants	7 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Week 24 · 70% Independency	6 Participants	4 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Week 24 · 60% Independency	4 Participants	2 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Week 24 · 50% Independency	3 Participants	1 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Week 24 · 40% Independency	1 Participants	0 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Week 24 · 30% Independency	1 Participants	1 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Week 24 · 20% Independency	0 Participants	1 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Week 24 · 10% Independency	1 Participants	0 Participants
The Schwab and England Activities of Daily Living (SE-ADL) Scale. Week 24 · 0% Independency	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Change from Baseline to Week 24

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.

Outcome measures

Outcome measures
Measure	GRF6021 n=43 Participants Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13. GRF6021: GRF6021 for IV infusion	Placebo n=21 Participants Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13. Placebo: Placebo for IV infusion
The Clinical Impression of Severity Index - PD (CISI-PD).	-0.54 change from baseline score Interval -1.91 to 0.83	-0.55 change from baseline score Interval -2.34 to 1.24

SECONDARY outcome

Timeframe: Change from Baseline to Week 20

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.

Outcome measures

Outcome measures
Measure	GRF6021 n=40 Participants Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13. GRF6021: GRF6021 for IV infusion	Placebo n=18 Participants Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13. Placebo: Placebo for IV infusion
The Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39).	-4.88 score on a scale Interval -11.46 to 1.69	-6.29 score on a scale Interval -14.81 to 2.23

SECONDARY outcome

Timeframe: Change from Baseline to Week 20

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.

Outcome measures

Outcome measures
Measure	GRF6021 n=41 Participants Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13. GRF6021: GRF6021 for IV infusion	Placebo n=20 Participants Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13. Placebo: Placebo for IV infusion
The Geriatric Depression Scale-15 (GDS-15).	0.30 score on a scale Interval -1.3 to 1.89	0.27 score on a scale Interval -1.74 to 2.27

SECONDARY outcome

Timeframe: Change from Baseline to Week 20

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.

Outcome measures

Outcome measures
Measure	GRF6021 n=36 Participants Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13. GRF6021: GRF6021 for IV infusion	Placebo n=20 Participants Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13. Placebo: Placebo for IV infusion
The Digital Clock Drawing Test (dCDT).	9.25 score on a scale Interval 1.69 to 16.8	1.58 score on a scale Interval -7.61 to 10.77

SECONDARY outcome

Timeframe: Change from Baseline to Week 20

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.

Outcome measures

Outcome measures
Measure	GRF6021 n=35 Participants Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13. GRF6021: GRF6021 for IV infusion	Placebo n=16 Participants Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13. Placebo: Placebo for IV infusion
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. Power of Attention	28.14 ms Standard Error 90.89	133.32 ms Standard Error 90.89
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. Cognitive Reaction Time	-49.49 ms Standard Error 75.69	35.45 ms Standard Error 75.69
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. Speed of Memory	46.97 ms Standard Error 331.56	232.33 ms Standard Error 331.56

Adverse Events

GRF6021

Serious events: 5 serious events

Other events: 45 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GRF6021 n=51 participants at risk Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13. GRF6021: GRF6021 for IV infusion	Placebo n=25 participants at risk Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13. Placebo: Placebo for IV infusion
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast Cancer	2.0% 1/51 • Number of events 1 • 24 Months	0.00% 0/25 • 24 Months
Injury, poisoning and procedural complications Road Traffic Accident	2.0% 1/51 • Number of events 1 • 24 Months	0.00% 0/25 • 24 Months
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	2.0% 1/51 • Number of events 1 • 24 Months	0.00% 0/25 • 24 Months
General disorders Gastritis	2.0% 1/51 • Number of events 1 • 24 Months	0.00% 0/25 • 24 Months
Psychiatric disorders Mental Changes	2.0% 1/51 • Number of events 1 • 24 Months	0.00% 0/25 • 24 Months

Other adverse events

Other adverse events
Measure	GRF6021 n=51 participants at risk Subjects will receive GRF6021 for 5 consecutive days at Week 1 and Week 13. GRF6021: GRF6021 for IV infusion	Placebo n=25 participants at risk Subjects will receive Placebo for 5 consecutive days at Week 1 and Week 13. Placebo: Placebo for IV infusion
Nervous system disorders Headache	15.7% 8/51 • Number of events 8 • 24 Months	8.0% 2/25 • Number of events 2 • 24 Months
Nervous system disorders Dizziness	9.8% 5/51 • Number of events 5 • 24 Months	4.0% 1/25 • Number of events 1 • 24 Months
Investigations Blood pressure diastolic decreased	3.9% 2/51 • Number of events 2 • 24 Months	16.0% 4/25 • Number of events 4 • 24 Months
Vascular disorders Hypotension	11.8% 6/51 • Number of events 6 • 24 Months	8.0% 2/25 • Number of events 2 • 24 Months
Vascular disorders Hypertension	3.9% 2/51 • Number of events 2 • 24 Months	8.0% 2/25 • Number of events 2 • 24 Months
Musculoskeletal and connective tissue disorders Arthralgia	7.8% 4/51 • Number of events 4 • 24 Months	0.00% 0/25 • 24 Months
Musculoskeletal and connective tissue disorders Back Pain	2.0% 1/51 • Number of events 1 • 24 Months	12.0% 3/25 • Number of events 3 • 24 Months
Infections and infestations Upper respiratory tract infection	7.8% 4/51 • Number of events 4 • 24 Months	4.0% 1/25 • Number of events 1 • 24 Months
Gastrointestinal disorders Diarrhoea	5.9% 3/51 • Number of events 3 • 24 Months	4.0% 1/25 • Number of events 1 • 24 Months
Injury, poisoning and procedural complications Fall	13.7% 7/51 • Number of events 7 • 24 Months	4.0% 1/25 • Number of events 1 • 24 Months
Injury, poisoning and procedural complications Laceration	5.9% 3/51 • Number of events 3 • 24 Months	4.0% 1/25 • Number of events 1 • 24 Months
General disorders Oedema peripheral	3.9% 2/51 • Number of events 2 • 24 Months	8.0% 2/25 • Number of events 2 • 24 Months

Additional Information

Head of Communications

Alkahest, Inc.

Phone: (650) 801-0474

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER