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

A Prospective, Randomized, Double-Blind, Dose-Comparison Concurrent Control Study to Assess the Safety and Tolerability of GRF6019 Infusions in Subjects With Mild to Moderate Alzheimer's Disease

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03520998

Enrollment

Registered

2018-05-11

Start date

2018-04-16

Completion date

2019-05-24

Last updated

2021-01-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Alzheimer Disease, Mild to Moderate Alzheimer Disease

Brief summary

This study is evaluating the safety, tolerability, and feasibility of GRF6019, a plasma-derived product, administered as an intravenous (IV) infusion, to subjects with mild to moderate Alzheimer's disease.

Detailed description

This is a randomized, double-blind, dose-comparison concurrent control study to assess the safety, tolerability, and feasibility of GRF6019, a plasma-derived product, administered by intravenous (IV) infusion to subjects with mild to moderate Alzheimer's disease. Subjects will be randomized 1:1 to a low dose or a high dose of active treatment in a double-blind manner. All subjects will receive one infusion per day at the randomized dose for 5 consecutive days during Week 1 and, again, during Week 13 (for a total of 10 doses per subject). All IV infusions will take place at an inpatient research unit while the follow-up visits after each treatment period will be on an outpatient basis. Subjects will participate for a total of 6 months in this study.

Interventions

DRUGGRF6019

GRF6019 for IV infusion

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

60 Years to 90 Years

Healthy volunteers

Inclusion criteria

* Diagnosis of probable AD based upon the National Institute on Aging-Alzheimer's Association (NIA-AA) Criteria * MMSE Score 12-24 inclusive * Modified Hachinski Ischemia Scale (MHIS) score of ≤ 4 * Provided a signed and dated informed consent form (either the subject and/or subject's legal representative as well as the trial partner)

Exclusion criteria

* Evidence of clinically relevant neurological disorder(s) other than probable AD * History of blood coagulation disorders or hypercoagulability; any concurrent use of an anticoagulant therapy. (e.g., heparin, warfarin, thrombin inhibitors, Factor Xa inhibitors). Use of antiplatelet drugs (e.g., aspirin or clopidogrel) is acceptable. * Initiation or change in the dosage of cholinesterase inhibitors (AChEI), memantine, Axona, vitamin E supplementation or selegiline within 3 months prior to screening. * Heart disease (or history thereof), as evidenced by myocardial infarction, unstable, new onset or severe angina, or congestive heart failure (New York Association Class II, III or IV) in the 6 months prior to dosing; uncontrolled high blood pressure (systolic blood pressure of 160 mmHg or higher and/or diastolic blood * Prior hypersensitivity reaction to any human blood product or intravenous infusion; any known clinically significant drug allergy. * Treatment with any human blood product, including transfusions and intravenous immunoglobulin, during the 6 months prior to screening. * History of immunoglobulin A (IgA), haptoglobulin or C1 inhibitor deficiency; stroke, anaphylaxis, or thromboembolic complications of intravenous immunoglobulins. * Hemoglobin \<10 g/dL in women; and \<11 g/dL in men.

Design outcomes

Primary

Measure	Time frame	Description
Frequency of Treatment-emergent Adverse Events (Safety)	Baseline to 6 months	Treatment-emergent adverse events identified by MedDRA preferred term and grouped by MedDRA System Organ Class

Secondary

Measure	Time frame	Description
The Mini-Mental State Examination (MMSE)	Baseline and 6 months	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.
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADASCog/11)	Baseline and 6 months	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.
The Clinical Dementia Rating Scale - Sum of Boxes (CDR-SOB)	Baseline and 6 months	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.
The Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23)	Baseline and 6 months	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.
The Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC)	Baseline and 6 months	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.
The Neuropsychiatric Inventory Questionnaire (NPI-Q)	Baseline and 6 months	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
GRF6019 Low Dose Low dose of GRF6019 for 5 consecutive days at Weeks 1 and 13	24
GRF6019 High Dose High dose of GRF6019 for 5 consecutive days at Weeks 1 and 13	23
Total	47

Baseline characteristics

Characteristic	GRF6019 Low Dose	Total	GRF6019 High Dose
Age, Continuous	75.9 years STANDARD_DEVIATION 6.26	74.3 years STANDARD_DEVIATION 6.85	72.7 years STANDARD_DEVIATION 7.21
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants	15 Participants	7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants	32 Participants	16 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Black or African American	1 Participants	4 Participants	3 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	23 Participants	42 Participants	19 Participants
Region of Enrollment United States	24 participants	47 participants	23 participants
Sex: Female, Male Female	15 Participants	29 Participants	14 Participants
Sex: Female, Male Male	9 Participants	18 Participants	9 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 24	0 / 23
other Total, other adverse events	12 / 24	14 / 23
serious Total, serious adverse events	0 / 24	2 / 23

Outcome results

Primary

Frequency of Treatment-emergent Adverse Events (Safety)

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

Time frame: Baseline to 6 months

Population: Safety Set

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
GRF6019 Low Dose	Frequency of Treatment-emergent Adverse Events (Safety)	18 Participants
GRF6019 High Dose	Frequency of Treatment-emergent Adverse Events (Safety)	20 Participants

Secondary

Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADASCog/11)

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.

Time frame: Baseline and 6 months