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This study will evaluate the safety, tolerability, and potential cognitive benefit of the experimental treatment GRF6019 in subjects with severe Alzheimer's disease.
This is a randomized, double-blind, placebo-controlled study to assess the safety, tolerability and potential cognitive benefit of GRF6019, a human plasma protein fraction. GRF6019 or placebo will be administered intravenously to subjects with severe Alzheimer's disease every day for 5 consecutive days. The total study duration for each subject is approximately 9 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GRF6019 | Experimental | Subjects will receive intravenously 250 mL of GRF6019 each day for 5 consecutive days. |
|
| Placebo | Placebo Comparator | Subjects will receive intravenously 250 mL of placebo each day for 5 consecutive days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GRF6019 | Drug | GRF6019 for IV infusion |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Frequency of Treatment-emergent Adverse Events (Safety) | Number of Subjects with at Least One Treatment-emergent adverse event by MedDRA preferred term and grouped by MedDRA System Organ Class | 5 weeks |
| Tolerability of GRF6019 | Tolerability of treatment defined by the number of subjects completing 4 weeks of study after receiving 5 daily infusions | 5 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| The Mini-Mental State Examination (MMSE) Score | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alkahest Program Physician | Alkahest, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cognitive Clinical Trials | Gilbert | Arizona | 85297 | United States | ||
| Cognitive Clinical Trials |
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| ID | Title | Description |
|---|---|---|
| FG000 | GRF6019 | GRF6019 250 mL IV for 5 consecutive days |
| FG001 | Placebo | Placebo 250 mL IV for 5 consecutive days |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | GRF6019 | GRF6019 250 mL IV for 5 consecutive days |
| BG001 | Placebo | Placebo 250 mL IV for 5 consecutive days |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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) | Number of Subjects with at Least One Treatment-emergent adverse event by MedDRA preferred term and grouped by MedDRA System Organ Class | Safety: All subjects who received any amount of study treatment | Posted | Count of Participants | Participants | 5 weeks |
|
5 weeks
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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 | GRF6019 250 mL IV for 5 consecutive days | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Head of Communications | Alkahest, Inc. | (650) 801-0474 | info@alkahest.com |
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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 | Jul 10, 2019 | Dec 9, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 11, 2019 | Dec 9, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D001927 | Brain Diseases |
| D009422 | Nervous System Diseases |
| D002493 | Central Nervous System Diseases |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003704 | Dementia |
| D024801 | Tauopathies |
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| ID | Term |
|---|---|
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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| Other |
Placebo for IV infusion |
|
|
| Baseline and 5 weeks |
| Severe Impairment Battery (SIB) Total Score | 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. | Baseline and 5 weeks |
| Alzheimer's Disease Cooperative Study Group Activities of Daily Living Inventory for Severe Alzheimer's Disease (ADCS-ADL-Severe) | 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. | Baseline and 5 weeks |
| Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change Plus Caregiver Input (ADCS-CGIC) | 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. | Baseline and 5 weeks |
| Neuropsychiatric Inventory Nursing Home (NPI-NH) Total Score | 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. | Baseline and 5 weeks |
| Neuropsychiatric Inventory (NPI) Caregiver Total Score | 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. | Baseline and 5 weeks |
| Mesa |
| Arizona |
| 85209 |
| United States |
| Cognitive Clinical Trials | Phoenix | Arizona | 85037 | United States |
| Pacific Research Network | San Diego | California | 92103 | United States |
| Riverside Clinical Research | Edgewater | Florida | 32132 | United States |
| Bio Behavioral Health | Toms River | New Jersey | 08755 | United States |
| BG002 |
| Total |
Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Duration of Alzheimer's Disease | Years of Alzheimer's Disease Duration calculated from Medical History Year of Diagnosis to Year of Informed Consent | Mean | Standard Deviation | years |
|
| Units | Counts |
|---|
| Participants |
|
|
| Primary | Tolerability of GRF6019 | Tolerability of treatment defined by the number of subjects completing 4 weeks of study after receiving 5 daily infusions | Safety: All subjects who received any amount of study treatment | Posted | Count of Participants | Participants | 5 weeks |
|
|
|
| Secondary | The Mini-Mental State Examination (MMSE) Score | 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. | Evaluable: Subjects who received at least 4 of the 5 planned infusions | Posted | Mean | Standard Deviation | score on a scale | Baseline and 5 weeks |
|
|
|
| Secondary | Severe Impairment Battery (SIB) Total Score | 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. | Evaluable: Subjects who received at least 4 of the 5 planned infusions | Posted | Mean | Standard Deviation | score on a scale | Baseline and 5 weeks |
|
|
|
| Secondary | Alzheimer's Disease Cooperative Study Group Activities of Daily Living Inventory for Severe Alzheimer's Disease (ADCS-ADL-Severe) | 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. | Evaluable: Subjects who received at least 4 of the 5 planned infusions | Posted | Mean | Standard Deviation | score on a scale | Baseline and 5 weeks |
|
|
|
| Secondary | Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change Plus Caregiver Input (ADCS-CGIC) | 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. | Evaluable: Subjects who received at least 4 of the 5 planned infusions | Posted | Mean | Standard Deviation | score on a scale | Baseline and 5 weeks |
|
|
|
| Secondary | Neuropsychiatric Inventory Nursing Home (NPI-NH) Total Score | 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. | Evaluable: Subjects who received at least 4 of the 5 planned infusions | Posted | Mean | Standard Deviation | score on a scale | Baseline and 5 weeks |
|
|
|
| Secondary | Neuropsychiatric Inventory (NPI) Caregiver Total Score | 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. | Evaluable: Subjects who received at least 4 of the 5 planned infusions | Posted | Mean | Standard Deviation | score on a scale | Baseline and 5 weeks |
|
|
|
| 18 |
| 0 |
| 18 |
| 8 |
| 18 |
| EG001 | Placebo | Placebo 250 mL IV for 5 consecutive days | 0 | 8 | 0 | 8 | 3 | 8 |
| Nausea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
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| Oedema | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Injection site swelling | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Blood creatinine phosphokinase increased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Blood pressure increased | Investigations | MedDRA 21.1 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
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| Sinus bradycardia | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
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| Tooth extraction | Surgical and medical procedures | MedDRA 21.1 | Systematic Assessment |
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