Severe Alzheimer DiseasePhase 2NCT03765762
A Study to Assess the Safety of GRF6019 Infusions in Subjects With Severe Alzheimer's Disease
A Phase 2 study testing GRF6019 in people with Severe Alzheimer Disease, run by Alkahest, Inc. at 6 sites in United States.
Trial summary
This study will evaluate the safety, tolerability, and potential cognitive benefit of the experimental treatment GRF6019 in subjects with severe Alzheimer's disease. Read more about this study
- Who is it for?
- Ages 60 to 95 years
- Conditions the study is for
- Severe Alzheimer Disease
- What is being tested?
- GRF6019
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 6 sitesUnited States
- Study dates
- 15 Jan 2019to 17 Dec 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of probable AD according to the National Institute on Aging-Alzheimer's Association (NIA-AA) Criteria
- MMSE Score 0-10 inclusive
- Modified Hachinski Ischemia Scale (MHIS) score of 4 or less
- Provided a signed and dated informed consent form (either the subject and/or subject's legal representative)
Who cannot join
- 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.
- Unstable coronary heart disease, e.g. myocardial infarction or severe or unstable angina in the 6 months prior to dosing.
- Moderate to severe congestive heart failure (New York Association Class III or IV).
- Poorly controlled high blood pressure (systolic blood pressure of 160 mmHg or higher and/or diastolic blood pressure of 100 mmHg or higher) despite treatment during the 3 months prior to dosing, or treatment refractory high blood pressure, defined as treatment requiring 3 or more antihypertensives from different classes.
- Prior hypersensitivity reaction to any human blood product or intravenous infusion; any known clinically significant drug allergy.
Show all 9Show fewer
- 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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Riverside Clinical Research
Edgewater, Florida, 32132
Cognitive Clinical Trials
Gilbert, Arizona, 85297
Cognitive Clinical Trials
Mesa, Arizona, 85209
Cognitive Clinical Trials
Phoenix, Arizona, 85037
Pacific Research Network
San Diego, California, 92103
Bio Behavioral Health
Toms River, New Jersey, 08755
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Tolerability of Pulsed GRF6019 Infusions in Subjects With Severe Alzheimer's Disease
This study will evaluate the safety, tolerability, and potential cognitive benefit of the experimental treatment GRF6019 in subjects with severe Alzheimer's disease.
Read the detailed description
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.
- Conditions
- Severe Alzheimer Disease
- Being tested
- GRF6019, Placebo
- Keywords
- Brain Diseases, Nervous System Diseases, Central Nervous System Diseases, Neurodegenerative Diseases, Neurocognitive Disorders, Mental Disorders, Dementia, Tauopathy
- Medical subject headings
- Alzheimer Disease, Brain Diseases, Nervous System Diseases, Central Nervous System Diseases, Neurodegenerative Diseases, Neurocognitive Disorders, Mental Disorders, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GRF6019Drug
GRF6019 for IV infusion
PlaceboOther
Also called Normal Saline
Placebo for IV infusion
| Study group | Role | What they receive |
|---|---|---|
| GRF6019 | Experimental | Subjects will receive intravenously 250 mL of GRF6019 each day for 5 consecutive days. Receives: Drug: GRF6019 |
| Placebo | Placebo comparator | Subjects will receive intravenously 250 mL of placebo each day for 5 consecutive days. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 5 weeks
Tolerability of GRF6019
Tolerability of treatment defined by the number of subjects completing 4 weeks of study after receiving 5 daily infusions
Measured: 5 weeks
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline and 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2018
- Study start15 Jan 2019
- Primary completion17 Dec 2019
- Study completion17 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Severe Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alkahest, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alkahest Program Physician, Study director, Alkahest, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03765762
- Sponsor's protocol ID
- Alkahest study 6019-202
- Status last verified
- May 2019
- First submitted
- 29 Nov 2018
- Last updated
- 27 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Tolerability of Pulsed GRF6019 Infusions in Subjects With Severe Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT03765762
- Acronym / sponsor ID
- Alkahest study 6019-202
- Conditions
- Severe Alzheimer Disease
- Keywords
- Brain Diseases, Nervous System Diseases, Central Nervous System Diseases, Neurodegenerative Diseases, Neurocognitive Disorders, Mental Disorders, Dementia, Tauopathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Alkahest, Inc.Industry (pharma, biotech, devices)
- Study start
- 15 Jan 2019 (actual)
- Primary completion
- 17 Dec 2019 (actual)
- Study completion
- 17 Dec 2019 (actual)
- First posted
- 5 Dec 2018 (actual)
- Results
- Posted 27 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety, tolerability, and potential cognitive benefit of the experimental treatment GRF6019 in subjects with severe Alzheimer's disease.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GRF6019 | Experimental | Drug: GRF6019Subjects will receive intravenously 250 mL of GRF6019 each day for 5 consecutive days. |
| Placebo | Placebo comparator | Other: PlaceboSubjects will receive intravenously 250 mL of placebo each day for 5 consecutive days. |
Who may qualify
- Ages
- 60 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of probable AD according to the National Institute on Aging-Alzheimer's Association (NIA-AA) Criteria
- MMSE Score 0-10 inclusive
- Modified Hachinski Ischemia Scale (MHIS) score of 4 or less
- Provided a signed and dated informed consent form (either the subject and/or subject's legal representative)
Key exclusion criteria (9 listed)
- 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.
- Unstable coronary heart disease, e.g. myocardial infarction or severe or unstable angina in the 6 months prior to dosing.
- Moderate to severe congestive heart failure (New York Association Class III or IV).
- Poorly controlled high blood pressure (systolic blood pressure of 160 mmHg or higher and/or diastolic blood pressure of 100 mmHg or higher) despite treatment during the 3 months prior to dosing, or treatment refractory high blood pressure, defined as treatment requiring 3 or more antihypertensives from different classes.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GRF6019GRF6019 for IV infusion | Drug | GRF6019 |
| PlaceboAlso: Normal SalinePlacebo for IV infusion | Other | Placebo |
Primary outcome
Frequency of Treatment-emergent Adverse Events (Safety)
Time frame: 5 weeks
Number of Subjects with at Least One Treatment-emergent adverse event by MedDRA preferred term and grouped by MedDRA System Organ Class
Tolerability of GRF6019
Time frame: 5 weeks
Tolerability of treatment defined by the number of subjects completing 4 weeks of study after receiving 5 daily infusions
6 secondary outcomes
The Mini-Mental State Examination (MMSE) Score
Time frame: Baseline and 5 weeks
Severe Impairment Battery (SIB) Total Score
Time frame: Baseline and 5 weeks
Alzheimer's Disease Cooperative Study Group Activities of Daily Living Inventory for Severe Alzheimer's Disease (ADCS-ADL-Severe)
Time frame: Baseline and 5 weeks
Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change Plus Caregiver Input (ADCS-CGIC)
Time frame: Baseline and 5 weeks
Neuropsychiatric Inventory Nursing Home (NPI-NH) Total Score
Time frame: Baseline and 5 weeks
Neuropsychiatric Inventory (NPI) Caregiver Total Score
Time frame: Baseline and 5 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alkahest Program Physician study director
Alkahest, Inc.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GRF6019 in people with Severe Alzheimer Disease, run by Alkahest, Inc. at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of Treatment-emergent Adverse Events (Safety) (time frame: 5 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2021.