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

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ClinicalTrials.gov Identifier: NCT03765762
Recruitment Status : Completed
First Posted : December 5, 2018
Results First Posted : January 27, 2021
Last Update Posted : January 27, 2021
Sponsor:
Information provided by (Responsible Party):
Alkahest, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Severe Alzheimer Disease
Interventions Drug: GRF6019
Other: Placebo
Enrollment 26
Recruitment Details  
Pre-assignment Details  
Arm/Group Title GRF6019 Placebo
Hide Arm/Group Description GRF6019 250 mL IV for 5 consecutive days Placebo 250 mL IV for 5 consecutive days
Period Title: Overall Study
Started 18 8
Completed 18 8
Not Completed 0 0
Arm/Group Title GRF6019 Placebo Total
Hide Arm/Group Description GRF6019 250 mL IV for 5 consecutive days Placebo 250 mL IV for 5 consecutive days Total of all reporting groups
Overall Number of Baseline Participants 18 8 26
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants 8 participants 26 participants
75.2  (8.25) 69.5  (8.12) 73.5  (8.49)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 8 participants 26 participants
Female
11
  61.1%
5
  62.5%
16
  61.5%
Male
7
  38.9%
3
  37.5%
10
  38.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 8 participants 26 participants
Hispanic or Latino
0
   0.0%
1
  12.5%
1
   3.8%
Not Hispanic or Latino
18
 100.0%
7
  87.5%
25
  96.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 8 participants 26 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   5.6%
0
   0.0%
1
   3.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
17
  94.4%
8
 100.0%
25
  96.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 18 participants 8 participants 26 participants
18 8 26
Duration of Alzheimer's Disease   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants 8 participants 26 participants
5.0  (1.81) 6.0  (3.59) 5.3  (2.46)
[1]
Measure Description: Years of Alzheimer's Disease Duration calculated from Medical History Year of Diagnosis to Year of Informed Consent
1.Primary Outcome
Title Frequency of Treatment-emergent Adverse Events (Safety)
Hide Description Number of Subjects with at Least One Treatment-emergent adverse event by MedDRA preferred term and grouped by MedDRA System Organ Class
Time Frame 5 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety: All subjects who received any amount of study treatment
Arm/Group Title GRF6019 Placebo
Hide Arm/Group Description:
GRF6019 250 mL IV for 5 consecutive days
Placebo 250 mL IV for 5 consecutive days
Overall Number of Participants Analyzed 18 8
Measure Type: Count of Participants
Unit of Measure: Participants
8
  44.4%
3
  37.5%
2.Primary Outcome
Title Tolerability of GRF6019
Hide Description Tolerability of treatment defined by the number of subjects completing 4 weeks of study after receiving 5 daily infusions
Time Frame 5 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety: All subjects who received any amount of study treatment
Arm/Group Title GRF6019 Placebo
Hide Arm/Group Description:
GRF6019 250 mL IV for 5 consecutive days
Placebo 250 mL IV for 5 consecutive days
Overall Number of Participants Analyzed 18 8
Measure Type: Count of Participants
Unit of Measure: Participants
18
 100.0%
8
 100.0%
3.Secondary Outcome
Title The Mini-Mental State Examination (MMSE) Score
Hide Description 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.
Time Frame Baseline and 5 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable: Subjects who received at least 4 of the 5 planned infusions
Arm/Group Title GRF6019 Placebo
Hide Arm/Group Description:
GRF6019 250 mL IV for 5 consecutive days
Placebo 250 mL IV for 5 consecutive days
Overall Number of Participants Analyzed 18 8
Mean (Standard Deviation)
Unit of Measure: score on a scale
1.3  (3.53) 1.8  (3.20)
4.Secondary Outcome
Title Severe Impairment Battery (SIB) Total Score
Hide Description 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.
Time Frame Baseline and 5 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable: Subjects who received at least 4 of the 5 planned infusions
Arm/Group Title GRF6019 Placebo
Hide Arm/Group Description:
GRF6019 250 mL IV for 5 consecutive days
Placebo 250 mL IV for 5 consecutive days
Overall Number of Participants Analyzed 18 8
Mean (Standard Deviation)
Unit of Measure: score on a scale
6.7  (7.59) 10.4  (4.93)
5.Secondary Outcome
Title Alzheimer's Disease Cooperative Study Group Activities of Daily Living Inventory for Severe Alzheimer's Disease (ADCS-ADL-Severe)
Hide Description 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.
Time Frame Baseline and 5 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable: Subjects who received at least 4 of the 5 planned infusions
Arm/Group Title GRF6019 Placebo
Hide Arm/Group Description:
GRF6019 250 mL IV for 5 consecutive days
Placebo 250 mL IV for 5 consecutive days
Overall Number of Participants Analyzed 18 8
Mean (Standard Deviation)
Unit of Measure: score on a scale
1.6  (5.05) 0.5  (4.93)
6.Secondary Outcome
Title Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change Plus Caregiver Input (ADCS-CGIC)
Hide Description 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.
Time Frame Baseline and 5 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable: Subjects who received at least 4 of the 5 planned infusions
Arm/Group Title GRF6019 Placebo
Hide Arm/Group Description:
GRF6019 250 mL IV for 5 consecutive days
Placebo 250 mL IV for 5 consecutive days
Overall Number of Participants Analyzed 18 8
Mean (Standard Deviation)
Unit of Measure: score on a scale
3.9  (0.83) 4.0  (0.76)
7.Secondary Outcome
Title Neuropsychiatric Inventory Nursing Home (NPI-NH) Total Score
Hide Description 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.
Time Frame Baseline and 5 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable: Subjects who received at least 4 of the 5 planned infusions
Arm/Group Title GRF6019 Placebo
Hide Arm/Group Description:
GRF6019 250 mL IV for 5 consecutive days
Placebo 250 mL IV for 5 consecutive days
Overall Number of Participants Analyzed 18 8
Mean (Standard Deviation)
Unit of Measure: score on a scale
-7.0  (19.16) -20.0  (5.66)
8.Secondary Outcome
Title Neuropsychiatric Inventory (NPI) Caregiver Total Score
Hide Description 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.
Time Frame Baseline and 5 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable: Subjects who received at least 4 of the 5 planned infusions
Arm/Group Title GRF6019 Placebo
Hide Arm/Group Description:
GRF6019 250 mL IV for 5 consecutive days
Placebo 250 mL IV for 5 consecutive days
Overall Number of Participants Analyzed 18 8
Mean (Standard Deviation)
Unit of Measure: score on a scale
-3.7  (11.60) 1.5  (4.32)
Time Frame 5 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title GRF6019 Placebo
Hide Arm/Group Description GRF6019 250 mL IV for 5 consecutive days Placebo 250 mL IV for 5 consecutive days
All-Cause Mortality
GRF6019 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/18 (0.00%)      0/8 (0.00%)    
Hide Serious Adverse Events
GRF6019 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/18 (0.00%)      0/8 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
GRF6019 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/18 (44.44%)      3/8 (37.50%)    
Cardiac disorders     
Sinus bradycardia  1  1/18 (5.56%)  1 0/8 (0.00%)  0
Gastrointestinal disorders     
Diarrhoea  1  2/18 (11.11%)  2 1/8 (12.50%)  1
Nausea  1  1/18 (5.56%)  1 1/8 (12.50%)  1
Vomiting  1  1/18 (5.56%)  1 0/8 (0.00%)  0
General disorders     
Oedema  1  1/18 (5.56%)  2 1/8 (12.50%)  1
Injection site swelling  1  1/18 (5.56%)  1 0/8 (0.00%)  0
Investigations     
Blood creatinine phosphokinase increased  1  1/18 (5.56%)  1 0/8 (0.00%)  0
Blood pressure increased  1  1/18 (5.56%)  1 0/8 (0.00%)  0
Nervous system disorders     
Dizziness  1  1/18 (5.56%)  1 0/8 (0.00%)  0
Psychiatric disorders     
Anxiety  1  0/18 (0.00%)  0 1/8 (12.50%)  2
Surgical and medical procedures     
Tooth extraction  1  1/18 (5.56%)  1 0/8 (0.00%)  0
Vascular disorders     
Hypotension  1  2/18 (11.11%)  3 1/8 (12.50%)  1
Hypertension  1  1/18 (5.56%)  1 0/8 (0.00%)  0
1
Term from vocabulary, MedDRA 21.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Head of Communications
Organization: Alkahest, Inc.
Phone: (650) 801-0474
EMail: info@alkahest.com
Layout table for additonal information
Responsible Party: Alkahest, Inc.
ClinicalTrials.gov Identifier: NCT03765762    
Other Study ID Numbers: Alkahest study 6019-202
First Submitted: November 29, 2018
First Posted: December 5, 2018
Results First Submitted: December 11, 2020
Results First Posted: January 27, 2021
Last Update Posted: January 27, 2021