Trial Outcomes & Findings for A Study to Assess the Safety of GRF6019 Infusions in Subjects With Severe Alzheimer's Disease (NCT NCT03765762)

NCT ID: NCT03765762

Last Updated: 2021-01-27

Results Overview

Number of Subjects with at Least One Treatment-emergent adverse event by MedDRA preferred term and grouped by MedDRA System Organ Class

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 26 participants
• Primary outcome timeframe: 5 weeks
• Results posted on: 2021-01-27

Participant Flow

Participant milestones

Measure	GRF6019 GRF6019 250 mL IV for 5 consecutive days	Placebo Placebo 250 mL IV for 5 consecutive days
Overall Study STARTED	18	8
Overall Study COMPLETED	18	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	GRF6019 n=18 Participants GRF6019 250 mL IV for 5 consecutive days	Placebo n=8 Participants Placebo 250 mL IV for 5 consecutive days	Total n=26 Participants Total of all reporting groups
Age, Continuous	75.2 years STANDARD_DEVIATION 8.25 • n=5 Participants	69.5 years STANDARD_DEVIATION 8.12 • n=7 Participants	73.5 years STANDARD_DEVIATION 8.49 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	5 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants	7 Participants n=7 Participants	25 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	1 Participants n=5 Participants	0 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	17 Participants n=5 Participants	8 Participants n=7 Participants	25 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	18 participants n=5 Participants	8 participants n=7 Participants	26 participants n=5 Participants
Duration of Alzheimer's Disease	5.0 years STANDARD_DEVIATION 1.81 • n=5 Participants	6.0 years STANDARD_DEVIATION 3.59 • n=7 Participants	5.3 years STANDARD_DEVIATION 2.46 • n=5 Participants

PRIMARY outcome

Timeframe: 5 weeks

Population: Safety: All subjects who received any amount of study treatment

Number of Subjects with at Least One Treatment-emergent adverse event by MedDRA preferred term and grouped by MedDRA System Organ Class

Outcome measures

Measure	GRF6019 n=18 Participants GRF6019 250 mL IV for 5 consecutive days	Placebo n=8 Participants Placebo 250 mL IV for 5 consecutive days
Frequency of Treatment-emergent Adverse Events (Safety)	8 Participants	3 Participants

PRIMARY outcome

Timeframe: 5 weeks

Population: Safety: All subjects who received any amount of study treatment

Tolerability of treatment defined by the number of subjects completing 4 weeks of study after receiving 5 daily infusions

Outcome measures

Measure	GRF6019 n=18 Participants GRF6019 250 mL IV for 5 consecutive days	Placebo n=8 Participants Placebo 250 mL IV for 5 consecutive days
Tolerability of GRF6019	18 Participants	8 Participants

SECONDARY outcome

Timeframe: Baseline and 5 weeks

Population: Evaluable: Subjects who received at least 4 of the 5 planned infusions

Mean change from Baseline to 5 Weeks in the Mini-Mental State Examination (MMSE) score. 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 mental status.

Outcome measures

Measure	GRF6019 n=18 Participants GRF6019 250 mL IV for 5 consecutive days	Placebo n=8 Participants Placebo 250 mL IV for 5 consecutive days
The Mini-Mental State Examination (MMSE) Score	1.3 score on a scale Standard Deviation 3.53	1.8 score on a scale Standard Deviation 3.20

SECONDARY outcome

Timeframe: Baseline and 5 weeks

Population: Evaluable: Subjects who received at least 4 of the 5 planned infusions

Mean change from baseline in the SIB total score. The SIB assesses cognition; test questions measure orientation, attention, language, praxis, visuospatial perception, construction, memory, orientation to name, and social interaction. There are 57 items and the range of possible scores is 0-133. Lower scores indicate greater cognitive impairment.

Outcome measures

Measure	GRF6019 n=18 Participants GRF6019 250 mL IV for 5 consecutive days	Placebo n=8 Participants Placebo 250 mL IV for 5 consecutive days
Severe Impairment Battery (SIB) Total Score	6.7 score on a scale Standard Deviation 7.59	10.4 score on a scale Standard Deviation 4.93

SECONDARY outcome

Timeframe: Baseline and 5 weeks

Population: Evaluable: Subjects who received at least 4 of the 5 planned infusions

Mean change from baseline in the ADCS-ADL-Severe score. The ADCS-ADL-Severe contains 19 items covering physical and mental functioning and independence in self-care and assesses the competence in performing basic activities of daily living. The scores range from 0 to 54, with higher scores indicating less functional impairment.

Outcome measures

Measure	GRF6019 n=18 Participants GRF6019 250 mL IV for 5 consecutive days	Placebo n=8 Participants Placebo 250 mL IV for 5 consecutive days
Alzheimer's Disease Cooperative Study Group Activities of Daily Living Inventory for Severe Alzheimer's Disease (ADCS-ADL-Severe)	1.6 score on a scale Standard Deviation 5.05	0.5 score on a scale Standard Deviation 4.93

SECONDARY outcome

Timeframe: Baseline and 5 weeks

Population: Evaluable: Subjects who received at least 4 of the 5 planned infusions

Mean ADCS-CGIC score. A CGIC score is based 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 rating of change and not of severity. It provides a semi structured format to enable clinicians to gather necessary clinical information from both the subject and informant to make a global impression of change. After completing the interviews, the clinician records the clinical impression of change on a 7-point Likert-type scale (from marked improvement to marked worsening). A score of 4 indicates no change, while scores > 4 indicate worsening and scores < 4 indicate improvement.

Outcome measures

Measure	GRF6019 n=18 Participants GRF6019 250 mL IV for 5 consecutive days	Placebo n=8 Participants Placebo 250 mL IV for 5 consecutive days
Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change Plus Caregiver Input (ADCS-CGIC)	3.9 score on a scale Standard Deviation 0.83	4.0 score on a scale Standard Deviation 0.76

SECONDARY outcome

Timeframe: Baseline and 5 weeks

Population: Evaluable: Subjects who received at least 4 of the 5 planned infusions

Mean change from Baseline to 5 weeks in the NPI-NH total score. The NPI-NH is a questionnaire that quantifies behavioral changes in dementia in nursing home patients and evaluates 12 behavioral domains (Delusions, Hallucinations, Agitation/Aggression, Depression/Dysphoria, Anxiety, Elation/Euphoria, Apathy/Indifference, Disinhibition, Irritability/Lability, Aberrant Motor Behavior, Sleep and Nighttime Behavior Disorders, Appetite/Eating Changes). For each of the 12 behavioral domains the Frequency (scale:1=occasionally to 4=very frequently) is multiplied by the Severity (scale:1=Mild to 3=Severe) to obtain a domain score (frequency x severity), with a possible summed total score of 0 to 144. Lower scores correspond to less severity. A negative change score from baseline indicates improvement.

Outcome measures

Measure	GRF6019 n=18 Participants GRF6019 250 mL IV for 5 consecutive days	Placebo n=8 Participants Placebo 250 mL IV for 5 consecutive days
Neuropsychiatric Inventory Nursing Home (NPI-NH) Total Score	-7.0 score on a scale Standard Deviation 19.16	-20.0 score on a scale Standard Deviation 5.66

SECONDARY outcome

Timeframe: Baseline and 5 weeks

Population: Evaluable: Subjects who received at least 4 of the 5 planned infusions

Mean change from Baseline to 5 Weeks in NPI Total Score. NPI is based on responses from the informed caregiver during an interview. It consists of 12 sub-domains (Delusions, Hallucinations, Agitation/Aggression, Dysphoria/Depression, Anxiety, Euphoria/Elation, Apathy/Indifference, Disinhibition, Irritability/Lability, Aberrant Motor, Nighttime Behavior, Appetite/Eating). For each of the 12 behavioral domains the Distress (scale:0=Not distressing at all to 5=Extreme) is multiplied by the Severity (scale:1=Mild to 3=Severe) to obtain a domain score (distress x severity), with a possible summed total score of 0 to 180. Lower scores correspond to less severity. A negative change score from baseline indicates improvement.

Outcome measures

Measure	GRF6019 n=18 Participants GRF6019 250 mL IV for 5 consecutive days	Placebo n=8 Participants Placebo 250 mL IV for 5 consecutive days
Neuropsychiatric Inventory (NPI) Caregiver Total Score	-3.7 score on a scale Standard Deviation 11.60	1.5 score on a scale Standard Deviation 4.32

Adverse Events

GRF6019

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	GRF6019 n=18 participants at risk GRF6019 250 mL IV for 5 consecutive days	Placebo n=8 participants at risk Placebo 250 mL IV for 5 consecutive days
Gastrointestinal disorders Diarrhoea	11.1% 2/18 • Number of events 2 • 5 weeks	12.5% 1/8 • Number of events 1 • 5 weeks
Gastrointestinal disorders Nausea	5.6% 1/18 • Number of events 1 • 5 weeks	12.5% 1/8 • Number of events 1 • 5 weeks
Gastrointestinal disorders Vomiting	5.6% 1/18 • Number of events 1 • 5 weeks	0.00% 0/8 • 5 weeks
Vascular disorders Hypotension	11.1% 2/18 • Number of events 3 • 5 weeks	12.5% 1/8 • Number of events 1 • 5 weeks
Vascular disorders Hypertension	5.6% 1/18 • Number of events 1 • 5 weeks	0.00% 0/8 • 5 weeks
General disorders Oedema	5.6% 1/18 • Number of events 2 • 5 weeks	12.5% 1/8 • Number of events 1 • 5 weeks
General disorders Injection site swelling	5.6% 1/18 • Number of events 1 • 5 weeks	0.00% 0/8 • 5 weeks
Investigations Blood creatinine phosphokinase increased	5.6% 1/18 • Number of events 1 • 5 weeks	0.00% 0/8 • 5 weeks
Investigations Blood pressure increased	5.6% 1/18 • Number of events 1 • 5 weeks	0.00% 0/8 • 5 weeks
Psychiatric disorders Anxiety	0.00% 0/18 • 5 weeks	12.5% 1/8 • Number of events 2 • 5 weeks
Cardiac disorders Sinus bradycardia	5.6% 1/18 • Number of events 1 • 5 weeks	0.00% 0/8 • 5 weeks
Nervous system disorders Dizziness	5.6% 1/18 • Number of events 1 • 5 weeks	0.00% 0/8 • 5 weeks
Surgical and medical procedures Tooth extraction	5.6% 1/18 • Number of events 1 • 5 weeks	0.00% 0/8 • 5 weeks

Additional Information

Head of Communications

Alkahest, Inc.

Phone: (650) 801-0474

Email: info@alkahest.com

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