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Clinical Trial
. 2023 Dec 13;15(1):215.
doi: 10.1186/s13195-023-01356-w.

NeuroEPO plus (NeuralCIM®) in mild-to-moderate Alzheimer's clinical syndrome: the ATHENEA randomized clinical trial

Saily Sosa  1 , Giosmany Bringas  2 , Nelky Urrutia  1 , Ana Ivis Peñalver  2 , Danay López  1 , Evelio González  3 , Ana Fernández  3 , Zenaida Milagros Hernández  4 , Ariel Viña  3 , Yamile Peña  5 , Juan Felipe Batista  5 , Carmen Valenzuela  6 , Kalet León  7 , Tania Crombet  7 , Teresita Rodríguez  7 , Leslie Pérez  8 ; ATHENEA Investigators
Collaborators, Affiliations
Clinical Trial

NeuroEPO plus (NeuralCIM®) in mild-to-moderate Alzheimer's clinical syndrome: the ATHENEA randomized clinical trial

Saily Sosa et al. Alzheimers Res Ther. .

Abstract

Background: NeuroEPO plus is a recombinant human erythropoietin without erythropoietic activity and shorter plasma half-life due to its low sialic acid content. NeuroEPO plus prevents oxidative damage, neuroinflammation, apoptosis and cognitive deficit in an Alzheimer's disease (AD) models. The aim of this study was to assess efficacy and safety of neuroEPO plus.

Methods: This was a double-blind, randomized, placebo-controlled, phase 2-3 trial involving participants ≥ 50 years of age with mild-to-moderate AD clinical syndrome. Participants were randomized in a 1:1:1 ratio to receive 0.5 or 1.0 mg of neuroEPO plus or placebo intranasally 3 times/week for 48 weeks. The primary outcome was change in the 11-item cognitive subscale of the AD Assessment Scale (ADAS-Cog11) score from baseline to 48 weeks (range, 0 to 70; higher scores indicate greater impairment). Secondary outcomes included CIBIC+, GDS, MoCA, NPI, Activities of Daily Living Scales, cerebral perfusion, and hippocampal volume.

Results: A total of 174 participants were enrolled and 170 were treated (57 in neuroEPO plus 0.5 mg, 56 in neuroEPO plus 1.0 mg and 57 in placebo group). Mean age, 74.0 years; 121 (71.2%) women and 85% completed the trial. The median change in ADAS-Cog11 score at 48 weeks was -3.0 (95% CI, -4.3 to -1.7) in the 0.5 mg neuroEPO plus group, -4.0 (95% CI, -5.9 to -2.1) in the 1.0 mg neuroEPO plus group and 4.0 (95% CI, 1.9 to 6.1) in the placebo group. The difference of neuroEPO plus 0.5 mg vs. placebo was 7.0 points (95% CI, 4.5-9.5) P = 0.000 and between the neuroEPO plus 1.0 mg vs. placebo was 8.0 points (95% CI, 5.2-10.8) P = 0.000. NeuroEPO plus treatment induced a statistically significant improvement in some of clinical secondary outcomes vs. placebo including CIBIC+, GDS, MoCA, NPI, and the brain perfusion.

Conclusions: Among participants with mild-moderate Alzheimer's disease clinical syndrome, neuroEPO plus improved the cognitive evaluation at 48 weeks, with a very good safety profile. Larger trials are warranted to determine the efficacy and safety of neuroEPO plus in Alzheimer's disease.

Trial registration: https://rpcec.sld.cu Identifier: RPCEC00000232.

Keywords: Alzheimer’s disease; NeuroEPO; Neuroprotective; Randomized controlled trial.

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Conflict of interest statement

K. León, T. Crombet, T. Rodríguez and L. Pérez are employees of Center of Molecular Immunology, the institution that produces the Investigational New Drug (IND). T. Rodríguez is one of the authors of the patent “Human recombinant hyposialylated erythropoietin, methods of purification and therapeutic uses thereof” PCT US2022/0305084; no further authors have anything to disclose.

Figures

Fig. 1
Fig. 1
Screening, randomization, and follow-up. Participants who completed at 48 weeks are considered to have completed the trial (per protocol population). The modified intention-to-treat population which included participants with at least one dose of neuroEPO plus or placebo and a baseline measurement based on randomized treatment. The per protocol population which included subjects who complied with the protocol sufficiently (more than 90% of treatment with efficacy outcomes at baseline and at 48 weeks without any major deviation of protocol) to ensure that these data would be likely to exhibit the effects of treatment according to the underlying scientific model. Subjects were considerate in their randomized group. The safety population included participants who received at least one dose of neuroEPO or placebo. SPECT denotes single-photon emission computed tomography
Fig. 2
Fig. 2
Primary and secondary outcomes from baseline to 48 weeks. Panels A and B show results in the modified intention-to-treat population (0.5 mg: n = 57; 1 mg: n = 56; Pb: n = 57). Panels C and D show results in the per protocol population (0.5 mg: n = 50; 1 mg: n = 49; Pb: n = 49). Panel A shows the results for the primary outcome, the score on the 11-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog11; range, 0 to 70, with higher scores indicating greater impairment). Panels B, C, and D show the results for the secondary outcomes. Panel B shows results for the change from baseline in the score on the Clinician Interview-Based Impression of Change Incorporating Caregiver Information (CIBIC+; range 0 to 7, with higher scores indicating greater impairment). Panel C shows results for the change from baseline in the score on the Montreal Cognitive Assessment (MoCA; normal ≥ 26/30, with lower scores indicating greater impairment). Panel D shows results for the change from baseline in the score on the Neuropsychiatric Inventory (NPI; range 0 to 120, higher scores reflect greater severity). 95% CIs for median changes were calculated (data was not approximated by normal distribution)
See this image and copyright information in PMC

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