NE3107 for Traumatic Brain Injury

Overseen By Jonathan Haroon

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Neurological Associates of West Los Angeles

Must not be taking: Sleep aids

Disqualifiers: Neurological, Psychiatric, Substance abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, NE3107 (also known as Bezisterim or HE3286), to determine if it can improve thinking and memory in individuals with a traumatic brain injury. The trial examines changes in brain function and specific body chemicals associated with inflammation. Participants will take NE3107 twice daily for six months. Individuals diagnosed with a traumatic brain injury who frequently experience fatigue or sleepiness might be suitable candidates for this trial. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that NE3107 is likely to be safe for humans?

Research has shown that NE3107 has undergone safety evaluations in several trials. In one study lasting seven months, participants generally tolerated NE3107 well, with no serious side effects directly linked to the treatment.

NE3107 is also under investigation for other conditions, such as Long COVID, with a focus on safety. Although specific results are not detailed, its testing in multiple trials suggests confidence in its safety.

This study is in its second phase, indicating that NE3107 showed promise in earlier safety evaluations. However, as with any treatment, individual experiences can differ, so discussing potential risks with a healthcare provider is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about NE3107 for treating Traumatic Brain Injury (TBI) because it offers a novel approach compared to existing treatments. Unlike the standard of care, which often involves symptomatic management and rehabilitation, NE3107 targets inflammation and insulin resistance, which are thought to contribute to the damage in TBI. This dual action could help in reducing both immediate and long-term impacts of brain injuries. Additionally, NE3107's potential to address the underlying mechanisms of TBI rather than just the symptoms is what makes it a promising option for improving outcomes in patients.

What evidence suggests that NE3107 might be an effective treatment for Traumatic Brain Injury?

Research has shown that NE3107 may enhance thinking and memory in some patients. In studies with Alzheimer's patients, those treated with NE3107 demonstrated potential improvements compared to those who received a placebo, suggesting it might aid brain-related issues. Although not all patients experienced significant benefits, some showed better thinking and daily functioning. This trial will explore whether NE3107 could also assist with traumatic brain injuries by reducing inflammation and improving metabolism. However, more research is necessary to confirm these benefits specifically for traumatic brain injury. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with traumatic brain injury confirmed by a medical professional. Participants must experience significant fatigue or sleepiness, as indicated by specific scores on the MFI and ESS or PSI scales. They need to be able to consent themselves or have someone who can consent for them, and commit to the study duration.

Inclusion Criteria

Multidimensional Fatigue Inventory (MFI) score of 27 or greater

I can commit to the full length of the study.

Epworth Sleepiness Scale (ESS) score of 10 or greater AND/OR a Pittsburgh Sleep Index (PSI) score of 5 or greater

Exclusion Criteria

I am not willing to use two forms of birth control.

My liver function tests are high, or I have a significant liver disease.

Significant language impairment with expressive or receptive aphasia

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 200mg BID of NE3107 for 6 months to evaluate its effects on sleep and fatigue in TBI subjects

6 months

Visits at Baseline, 3 months, and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NE3107

Trial Overview The trial is testing NE3107, focusing on its effects on improving cognition through verbal and visual tests, as well as assessing changes in biomarkers related to traumatic brain injury and various inflammatory and metabolic parameters.

How Is the Trial Designed?

Group I: Experimental Arm: NE3107 Experimental Treatment 1 Intervention

All participants will take 200mg BID (12 hours apart) of NE3107 for 6 months.

Who Is Running the Clinical Trial?

Neurological Associates of West Los Angeles

Lead Sponsor

Trials

26

Recruited

4,000+

BioVie Inc.

Industry Sponsor

Trials

8

Recruited

800+

Published Research Related to This Trial

In a study using male Wistar rats with mild traumatic brain injury (TBI), treatment with the hybrid molecule JM-20 significantly improved locomotor and exploratory activities, as well as short-term memory deficits, indicating its potential efficacy in TBI recovery.

JM-20 also demonstrated a neuroprotective effect by reducing brain edema and attenuating neuroinflammation, as it prevented the excessive activation of glial cells and restored levels of important neurotrophic factors like BDNF, GDNF, and NGF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JM-20 Treatment After Mild Traumatic Brain Injury Reduces Glial Cell Pro-inflammatory Signaling and Behavioral and Cognitive Deficits by Increasing Neurotrophin Expression. Furtado, ABV., Gonçalves, DF., Hartmann, DD., et al.[2022]

NNZ-2566, a tripeptide analogue, shows neuroprotective effects in traumatic brain injury models by significantly reducing inflammatory cytokines and enhancing the expression of the protective protein ATF3 in various cell types.

The treatment with NNZ-2566 not only increases ATF3 mRNA levels but also boosts protein expression in microglia, NK cells, and astrocytes, suggesting a mechanism by which it modulates neuroinflammation and promotes recovery after brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanism of action for NNZ-2566 anti-inflammatory effects following PBBI involves upregulation of immunomodulator ATF3. Cartagena, CM., Phillips, KL., Williams, GL., et al.[2021]

Memantine, a non-competitive NMDA receptor antagonist, was found to significantly prevent neuronal death in the hippocampal CA2 and CA3 regions of adult rats after traumatic brain injury, with reductions in cell loss of 50% and 59%, respectively.

This study is the first to demonstrate the neuroprotective effects of memantine following traumatic brain injury, suggesting its potential as a treatment to mitigate neuronal damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroprotection by memantine, a non-competitive NMDA receptor antagonist after traumatic brain injury in rats. Rao, VL., Dogan, A., Todd, KG., et al.[2019]

The selective 5-HT6R agonist WAY-181187 significantly improved cognitive function in rats after traumatic brain injury (TBI) when administered for five consecutive days, demonstrating its potential as a treatment for cognitive dysfunction post-TBI.

WAY-181187 increased brain-derived neurotrophic factor (BDNF) expression and enhanced neuroplasticity in the medial prefrontal cortex and hippocampus, which are critical areas for memory and learning, suggesting a mechanism of action that supports cognitive recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 5-HT6R agonist alleviates cognitive dysfunction after traumatic brain injury in rats by increasing BDNF expression. Ou, FY., Ning, YL., Yang, N., et al.[2022]

NNZ-2566, a synthetic neuroprotective compound, significantly reduced the expression of harmful inflammatory cytokines like IL-1beta and TNF-alpha in a rat model of traumatic brain injury, suggesting its potential to mitigate neuroinflammation.

The treatment was administered shortly after injury and demonstrated a clear ability to modulate neuroinflammatory responses, indicating that NNZ-2566 could play a crucial role in the recovery process following brain injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NNZ-2566 treatment inhibits neuroinflammation and pro-inflammatory cytokine expression induced by experimental penetrating ballistic-like brain injury in rats. Wei, HH., Lu, XC., Shear, DA., et al.[2021]

Citations

1. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/NE3107_UPDATE_2_%28drug_in_development%29.pdf

NE3107 (HE3286) NE3107 treatment did not significantly improve cognitive and functional scores in AD patients in a phase. 3 study that was underpowered; only a subset of ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05970575

Insulin-sensitizing NE3107 in Improving Sleep and Fatigue ... This study seeks to measure changes in cognition through verbal and visual test procedures and changes in biomarkers of Traumatic Brain Injury and inflammatory ...

3. mayo.edu mayo.edu/research/clinical-trials/cls-20586927

A Study of Bezisterim (NE3107) in Adults with Long COVID The purpose of this study is to evaluate the efficacy, safety, and tolerability of bezisterim (NE3107) oral capsules compared with matching placebo, in adult ...

4. investors.bioviepharma.com investors.bioviepharma.com/news/news-details/2023/BioVie-Announces-Efficacy-Data-from-Phase-3-Trial-of-NE3107-in-Patients-with-Mild-to-Moderate-Alzheimers-Disease-11-29-2023/default.aspx

BioVie Announces Efficacy Data from Phase 3 Trial of NE3107 ... Data from evaluable patients show NE3107's treatment advantage compared to placebo may be equal to or greater than the benefit from approved AD monoclonal ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12082838/

An exploratory analysis of bezisterim treatment associated ... Bezisterim was associated with non-significant directional improvements in multiple measures of cognitive and functional performance compared to placebo.

6. delta.larvol.com delta.larvol.com/Products/?ProductId=7e8f343f-343c-421e-82fe-98c9bfea4553

Triolex (bezisterim) / Harbor Biosci, BioVie Insulin-sensitizing NE3107 in Improving Sleep and Fatigue in Subjects With Traumatic Brain Injury (clinicaltrials.gov) - P2 | N=4 | Terminated | Sponsor ...