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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GRF6019 Low Dose | Experimental | Subjects will receive a low dose of GRF6019 for 5 consecutive days at Week 1 and Week 13. |
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| GRF6019 High Dose | Experimental | Subjects will receive a high dose of GRF6019 for 5 consecutive days at Week 1 and Week 13. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GRF6019 | Drug | GRF6019 for IV infusion |
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| Measure | Description | Time Frame |
|---|---|---|
| Frequency of Treatment-emergent Adverse Events (Safety) | Treatment-emergent adverse events identified by MedDRA preferred term and grouped by MedDRA System Organ Class | Baseline to 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| The Mini-Mental State Examination (MMSE) | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alkahest Medical Monitor | Alkahest, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Synergy East | Lemon Grove | California | 91945 | United States | ||
| CNS Network |
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| ID | Title | Description |
|---|---|---|
| FG000 | GRF6019 Low Dose | Low dose of GRF6019 for 5 consecutive days at Weeks 1 and 13 |
| FG001 | GRF6019 High Dose | High dose of GRF6019 for 5 consecutive days at Weeks 1 and 13 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 2, 2018 | Oct 8, 2020 |
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| Baseline and 6 months |
| 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. | Baseline and 6 months |
| The Clinical Dementia Rating Scale - Sum of Boxes (CDR-SOB) | 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. | Baseline and 6 months |
| The Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23) | 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. | Baseline and 6 months |
| The Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) | 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. | Baseline and 6 months |
| The Neuropsychiatric Inventory Questionnaire (NPI-Q) | 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. | Baseline and 6 months |
| Long Beach |
| California |
| 90806 |
| United States |
| Pacific Research Network | San Diego | California | 92103 | United States |
| MD Clinical | Hallandale | Florida | 33009 | United States |
| Miami Jewish Health Systems | Miami | Florida | 33137 | United States |
| Behavioral Clinical Research | North Miami | Florida | 33161 | United States |
| Bioclinica Research | Orlando | Florida | 32806 | United States |
| Princeton Medical Institute | Princeton | New Jersey | 08540 | United States |
| Serenity Inpatient | DeSoto | Texas | 75115 | United States |
| PRA Health Sciences | Salt Lake City | Utah | 84124 | United States |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | GRF6019 Low Dose | Low dose of GRF6019 for 5 consecutive days at Weeks 1 and 13 |
| BG001 | GRF6019 High Dose | High dose of GRF6019 for 5 consecutive days at Weeks 1 and 13 |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Frequency of Treatment-emergent Adverse Events (Safety) | Treatment-emergent adverse events identified by MedDRA preferred term and grouped by MedDRA System Organ Class | Safety Set | Posted | Count of Participants | Participants | Baseline to 6 months |
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| Secondary | The Mini-Mental State Examination (MMSE) | 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. | Evaluable Set and Per Protocol Set | Posted | Mean | Standard Deviation | score on a scale | Baseline and 6 months |
|
| |||||||||||||||||||||||||||||
| 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. | Evaluable Set and Per Protocol Set | Posted | Mean | Standard Deviation | score on a scale | Baseline and 6 months |
|
| |||||||||||||||||||||||||||||
| Secondary | The Clinical Dementia Rating Scale - Sum of Boxes (CDR-SOB) | 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. | Evaluable Set and Per Protocol Set | Posted | Mean | Standard Deviation | score on a scale | Baseline and 6 months |
|
| |||||||||||||||||||||||||||||
| Secondary | The Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23) | 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. | Evaluable Set and Per Protocol Set | Posted | Mean | Standard Deviation | score on a scale | Baseline and 6 months |
|
| |||||||||||||||||||||||||||||
| Secondary | The Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) | 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. | Evaluable Set and Per Protocol Set | Posted | Mean | Standard Deviation | score on a scale | Baseline and 6 months |
|
| |||||||||||||||||||||||||||||
| Secondary | The Neuropsychiatric Inventory Questionnaire (NPI-Q) | 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. | Evaluable Set and Per Protocol Set | Posted | Mean | Standard Deviation | score on a scale | Baseline and 6 months |
|
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6 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | GRF6019 Low Dose | Low dose of GRF6019 for 5 consecutive days at Weeks 1 and 13 | 0 | 24 | 0 | 24 | 12 | 24 |
| EG001 | GRF6019 High Dose | High dose of GRF6019 for 5 consecutive days at Weeks 1 and 13 | 0 | 23 | 2 | 23 | 14 | 23 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Infusion related reaction | Injury, poisoning and procedural complications | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infusion site extravasation | General disorders | Systematic Assessment |
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| Infusion site haematoma | General disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Amylase increased | Investigations | Systematic Assessment |
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| Lipase increased | Investigations | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Hypertension | Vascular disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Head of Communications | Alkahest, Inc. | (650) 801-0474 | info@alkahest.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 9, 2019 | Oct 8, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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