PMID- 33967047
OWN - NLM
STAT- MEDLINE
DCOM- 20210920
LR  - 20220429
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 81
IP  - 4
DP  - 2021
TI  - Safety and Tolerability of GRF6019 Infusions in Severe Alzheimer's Disease: A 
      Phase II Double-Blind Placebo-Controlled Trial.
PG  - 1649-1662
LID - 10.3233/JAD-210011 [doi]
AB  - BACKGROUND: The plasma fraction GRF6019 shows multiple benefits on brain aging in 
      mice, including enhanced cognition, neurogenesis, and synaptic density, as well 
      as reduced neuroinflammation. OBJECTIVE: To evaluate the safety, tolerability, 
      and preliminary efficacy of GRF6019 in patients with severe Alzheimer's disease 
      (AD). METHODS: A phase II, double-blind, placebo-controlled study in patients 
      with severe AD (Mini-Mental State Examination score 0-10). Patients were 
      randomized 2 : 1 to GRF6019 (N = 18) or placebo (N = 8) and received daily 250 mL 
      intravenous infusions over 5 days. The primary endpoints were the rates of 
      adverse events (AEs) and the tolerability of GRF6019 as assessed by the number of 
      patients completing the study. Change from baseline in cognitive and functional 
      assessments was also evaluated. RESULTS: All patients completed 100%of study 
      visits and infusions. The rate of AEs was similar in the GRF6019 (8/18 patients 
      [44.4%]) and placebo (3/8 patients [37.5%]) groups, and there were no deaths or 
      serious AEs. The most common AEs considered related to treatment were mild, 
      transient changes in blood pressure in the GRF6019 group (hypotension: 2 patients 
      [11.1%]; hypertension: 1 patient [5.6%]); there were no related AEs in the 
      placebo group. The trial was not powered to detect statistically significant 
      differences between treatment groups. At the end of the study, patients in both 
      treatment groups remained stable or improved on all cognitive and functional 
      endpoints. CONCLUSION: GRF6019 demonstrated excellent safety, feasibility, and 
      tolerability. Future trials designed to characterize the potential functional 
      benefits of GRF6019 and related plasma fractions in severe AD are warranted.
FAU - Hannestad, Jonas
AU  - Hannestad J
AD  - Alkahest Inc., San Carlos, CA, USA.
FAU - Duclos, Tiffanie
AU  - Duclos T
AD  - Alkahest Inc., San Carlos, CA, USA.
FAU - Chao, Whitney
AU  - Chao W
AD  - Alkahest Inc., San Carlos, CA, USA.
FAU - Koborsi, Katie
AU  - Koborsi K
AD  - Alkahest Inc., San Carlos, CA, USA.
FAU - Klutzaritz, Vicki
AU  - Klutzaritz V
AD  - Alkahest Inc., San Carlos, CA, USA.
FAU - Beck, Brian
AU  - Beck B
AD  - CCT Research, Scottsdale, Arizona, USA.
FAU - Patel, Ashok K
AU  - Patel AK
AD  - Bio Behavioral Health, Toms River, NJ, USA.
FAU - Scott, James
AU  - Scott J
AD  - Riverside Clinical Research, Edgewater, FL, USA.
FAU - Thein, Stephen G
AU  - Thein SG
AD  - Pacific Research Network -an ERG Portfolio Company, San Diego, CA, USA.
FAU - Cummings, Jeffrey L
AU  - Cummings JL
AD  - Chambers-Grundy Center for Transformative Neuroscience, Department of Brain 
      Health, School of Integrated Health Sciences, University of Nevada Las Vegas, Las 
      Vegas, NV, USA.
FAU - Kay, Gary
AU  - Kay G
AD  - Cognitive Research Corporation, St. Petersburg, FL, USA.
FAU - Braithwaite, Steven
AU  - Braithwaite S
AD  - Alkahest Inc., San Carlos, CA, USA.
FAU - Nikolich, Karoly
AU  - Nikolich K
AD  - Alkahest Inc., San Carlos, CA, USA.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Nootropic Agents)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/*drug therapy/psychology
MH  - Cognition/*drug effects
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - Mental Status and Dementia Tests
MH  - Middle Aged
MH  - Nootropic Agents/administration & dosage/*adverse effects/therapeutic use
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Aging
OT  - Alzheimer's disease
OT  - blood proteins
OT  - dementia
OT  - plasma
OT  - randomized controlled trial
EDAT- 2021/05/11 06:00
MHDA- 2021/09/21 06:00
CRDT- 2021/05/10 06:10
PHST- 2021/05/11 06:00 [pubmed]
PHST- 2021/09/21 06:00 [medline]
PHST- 2021/05/10 06:10 [entrez]
AID - JAD210011 [pii]
AID - 10.3233/JAD-210011 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2021;81(4):1649-1662. doi: 10.3233/JAD-210011.