Trial Outcomes & Findings for A Randomized Study to Assess the Safety of GRF6019 Infusions in Subjects With Mild to Moderate Alzheimer's Disease (NCT NCT03520998)

NCT ID: NCT03520998

Last Updated: 2021-01-29

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

47 participants

Primary outcome timeframe

Baseline to 6 months

Results posted on

2021-01-29

Participant Flow

Participant milestones

Participant milestones
Measure
GRF6019 Low Dose
Low dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
GRF6019 High Dose
High dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
Overall Study
STARTED
24
23
Overall Study
COMPLETED
18
21
Overall Study
NOT COMPLETED
6
2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Randomized Study to Assess the Safety of GRF6019 Infusions in Subjects With Mild to Moderate Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
GRF6019 Low Dose
n=24 Participants
Low dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
GRF6019 High Dose
n=23 Participants
High dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
Total
n=47 Participants
Total of all reporting groups
Age, Continuous
75.9 years
STANDARD_DEVIATION 6.26 • n=5 Participants
72.7 years
STANDARD_DEVIATION 7.21 • n=7 Participants
74.3 years
STANDARD_DEVIATION 6.85 • n=5 Participants
Sex: Female, Male
Female
15 Participants
n=5 Participants
14 Participants
n=7 Participants
29 Participants
n=5 Participants
Sex: Female, Male
Male
9 Participants
n=5 Participants
9 Participants
n=7 Participants
18 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
8 Participants
n=5 Participants
7 Participants
n=7 Participants
15 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
16 Participants
n=5 Participants
16 Participants
n=7 Participants
32 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
1 Participants
n=7 Participants
1 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
1 Participants
n=5 Participants
3 Participants
n=7 Participants
4 Participants
n=5 Participants
Race (NIH/OMB)
White
23 Participants
n=5 Participants
19 Participants
n=7 Participants
42 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
24 participants
n=5 Participants
23 participants
n=7 Participants
47 participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 6 months

Population: Safety Set

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

Outcome measures

Outcome measures
Measure
GRF6019 Low Dose
n=24 Participants
Low dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
GRF6019 High Dose
n=23 Participants
High dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
Frequency of Treatment-emergent Adverse Events (Safety)
18 Participants
20 Participants

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Evaluable Set and Per Protocol Set

Changes in scores on the MMSE. The MMSE consists of 5 components: orientation to time and place, registration of 3 words, attention and calculation, recall of 3 words, and language. The scores from the 5 components are summed to obtain the overall MMSE total score. The MMSE total score can range from 0 to 30, with higher scores indicating better cognition.

Outcome measures

Outcome measures
Measure
GRF6019 Low Dose
n=21 Participants
Low dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
GRF6019 High Dose
n=22 Participants
High dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
The Mini-Mental State Examination (MMSE)
-1.0 score on a scale
Standard Deviation 4.3
1.5 score on a scale
Standard Deviation 3.9

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Evaluable Set and Per Protocol Set

Changes in scores on the 11-item ADASCog/11. The ADAS-Cog/11 includes 11 items assessing cognitive function. The domains include memory, language, praxis, and orientation. There are 70 possible points. Higher scores reflect greater cognitive impairment.

Outcome measures

Outcome measures
Measure
GRF6019 Low Dose
n=21 Participants
Low dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
GRF6019 High Dose
n=22 Participants
High dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADASCog/11)
-0.4 score on a scale
Standard Deviation 5.1
-0.9 score on a scale
Standard Deviation 4.3

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Evaluable Set and Per Protocol Set

Changes in the CDR-SOB. The CDR characterizes functioning in 6 domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. The score is obtained by summing each of the domain box scores. Scores range from 0 to 18 with higher scores reflecting worse cognition.

Outcome measures

Outcome measures
Measure
GRF6019 Low Dose
n=21 Participants
Low dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
GRF6019 High Dose
n=22 Participants
High dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
The Clinical Dementia Rating Scale - Sum of Boxes (CDR-SOB)
-0.03 score on a scale
Standard Deviation 2.3
0.21 score on a scale
Standard Deviation 1.7

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Evaluable Set and Per Protocol Set

Changes in the ADCS-ADL23. The ADCS-ADL23 assesses basic and instrumental activities of daily living covering physical and mental functioning and independence in self-care. The score ranges from 0 to 78 with higher scores indicating less functional impairment.

Outcome measures

Outcome measures
Measure
GRF6019 Low Dose
n=21 Participants
Low dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
GRF6019 High Dose
n=22 Participants
High dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
The Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23)
-0.7 score on a scale
Standard Deviation 7.4
-1.3 score on a scale
Standard Deviation 4.6

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Evaluable Set and Per Protocol Set

The ADCS-CGIC focuses on clinicians' observations of change in the subject's cognitive, functional, and behavioral performance since the beginning of a trial. The ADCS-CGIC is a 7-point scale with lower values (\<4) representing an improvement, higher values (\>4) representing a worsening, and a value of 4 indicating no change.

Outcome measures

Outcome measures
Measure
GRF6019 Low Dose
n=21 Participants
Low dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
GRF6019 High Dose
n=22 Participants
High dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
The Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC)
4.1 score on a scale
Standard Deviation 0.8
4.1 score on a scale
Standard Deviation 0.7

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Evaluable Set and Per Protocol Set

Change on the NPI-Q. The NPI-Q comprises 12 domains: delusions, hallucinations, dysphoria, apathy, euphoria, disinhibition, aggressivity and restlessness, irritability, anxiety aberrant motor behavior, appetite and eating disorders, and nocturnal behavior. The severity of the reported symptoms is assessed on a 3-point scale. The total severity score can range from 0 to 36 with higher scores representing worse severity.

Outcome measures

Outcome measures
Measure
GRF6019 Low Dose
n=21 Participants
Low dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
GRF6019 High Dose
n=22 Participants
High dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
The Neuropsychiatric Inventory Questionnaire (NPI-Q)
-2.3 score on a scale
Standard Deviation 3.8
-1.2 score on a scale
Standard Deviation 3.1

Adverse Events

GRF6019 Low Dose

Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths

GRF6019 High Dose

Serious events: 2 serious events
Other events: 14 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
GRF6019 Low Dose
n=24 participants at risk
Low dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
GRF6019 High Dose
n=23 participants at risk
High dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
0.00%
0/24 • 6 months
4.3%
1/23 • Number of events 1 • 6 months
Injury, poisoning and procedural complications
Infusion related reaction
0.00%
0/24 • 6 months
4.3%
1/23 • Number of events 1 • 6 months

Other adverse events

Other adverse events
Measure
GRF6019 Low Dose
n=24 participants at risk
Low dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
GRF6019 High Dose
n=23 participants at risk
High dose of GRF6019 for 5 consecutive days at Weeks 1 and 13
General disorders
Infusion site extravasation
12.5%
3/24 • Number of events 3 • 6 months
8.7%
2/23 • Number of events 2 • 6 months
General disorders
Infusion site haematoma
4.2%
1/24 • Number of events 1 • 6 months
17.4%
4/23 • Number of events 4 • 6 months
Nervous system disorders
Headache
12.5%
3/24 • Number of events 4 • 6 months
21.7%
5/23 • Number of events 7 • 6 months
Investigations
Amylase increased
4.2%
1/24 • Number of events 1 • 6 months
8.7%
2/23 • Number of events 3 • 6 months
Investigations
Lipase increased
4.2%
1/24 • Number of events 1 • 6 months
8.7%
2/23 • Number of events 3 • 6 months
Gastrointestinal disorders
Diarrhoea
4.2%
1/24 • Number of events 1 • 6 months
8.7%
2/23 • Number of events 2 • 6 months
Injury, poisoning and procedural complications
Fall
4.2%
1/24 • Number of events 1 • 6 months
8.7%
2/23 • Number of events 2 • 6 months
Musculoskeletal and connective tissue disorders
Arthralgia
8.3%
2/24 • Number of events 2 • 6 months
0.00%
0/23 • 6 months
Vascular disorders
Hypertension
4.2%
1/24 • Number of events 1 • 6 months
8.7%
2/23 • Number of events 3 • 6 months

Additional Information

Head of Communications

Alkahest, Inc.

Phone: (650) 801-0474

Results disclosure agreements

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

Restriction type: LTE60