18F-OP-801 for ALS

Recruiting at 2 trial locations

Overseen By Julee Cheung

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Ashvattha Therapeutics, Inc.

Must not be taking: Corticosteroids, NSAIDs

Disqualifiers: Obesity, Alcoholism, Drug abuse, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 day

65 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new brain scan substance called 18F-OP-801 on patients with ALS, AD, MS, PD, and healthy volunteers. It helps doctors see brain inflammation by highlighting active immune cells. This could improve early detection and treatment of these diseases.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, any medication changes within 30 days prior to the Screening Visit should be discussed with the Medical Monitor for ALS, AD, MS, and PD subjects.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, any medication changes within 30 days prior to the Screening Visit should be discussed with the Medical Monitor, especially for ALS, AD, MS, and PD subjects.

What data supports the idea that 18F-OP-801 for ALS is an effective treatment?

The available research does not provide specific data on the effectiveness of 18F-OP-801 for ALS. Instead, it discusses the use of PET imaging as a tool to study ALS and mentions other treatments like riluzole, edaravone, and PB-TURSO. PB-TURSO showed a 6.5-month longer median survival compared to placebo in a study, suggesting it has benefits for ALS patients. However, there is no direct comparison or data on 18F-OP-801's effectiveness for ALS in the provided information. ^{1 2 3 4 5}

What data supports the effectiveness of the drug 18F-OP-801 for ALS?

The research highlights the potential of PET imaging as a biomarker for ALS, which can help in diagnosing and measuring the effects of drugs in the brain and spinal cord. While there is no direct evidence for 18F-OP-801, similar PET radioligands have shown promise in visualizing brain changes in ALS, suggesting potential utility in assessing treatment effects. ^{1 2 3 4 5}

What safety data is available for 18F-OP-801 in ALS treatment?

The provided research does not contain any safety data for 18F-OP-801, OP-801, PET Dendrimer, or 18F OP 801. The studies focus on different PET tracers and their applications, but none mention 18F-OP-801 or its safety evaluation. ^{6 7 8 9 10}

Is 18F-OP-801 a promising drug for ALS?

The information provided does not directly mention 18F-OP-801, so we can't say if it's promising. However, related studies show that certain imaging techniques using similar compounds can help understand ALS better, which might support future drug development. ^{3 4 11 12 13}

Research Team

Farshad Moradi, MD, PhD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for adults aged 18-80 with ALS, Alzheimer's, Parkinson's, or Multiple Sclerosis and healthy volunteers. Participants must have stable medication use and meet specific health criteria like normal C-reactive protein levels. Women of childbearing age must use effective contraception, as should men; women can't be pregnant or breastfeeding.

Inclusion Criteria

My MS disability score is between 2.0 and 5.5.

I agree to use birth control or abstain from sex.

I have ALS and can either breathe well enough or lie flat for 90 minutes.

Exclusion Criteria

Overall Exclusion Criteria - For All Subjects: Lost or donated >450 mL of whole blood or blood products within 30 days prior to Screening

I have not taken corticosteroids in the last 30 days.

Overall Exclusion Criteria - For All Subjects: Has any finding that would compromise the subject's safety in the trial

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive a single intravenous administration of 18F-OP-801 and undergo PET imaging to evaluate safety, PK, and biodistribution

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment-emergent adverse events and imaging repeatability

18-29 days

Multiple visits (in-person)

Treatment Details

Interventions

• 18F-OP-801

Trial Overview The study tests the safety and distribution in the body of a new PET imaging biomarker called 18F-OP-801. It aims to identify activated microglia/macrophages in areas affected by neuroinflammation in patients with neurological conditions compared to healthy individuals.

Participant Groups

Group I: Parkinson's Disease participants Experimental Treatment 1 Intervention

Intravenous Administration of 18F-OP-801 (18F Hydroxyl Dendrimer)

Group II: Multiple Sclerosis participants Experimental Treatment 1 Intervention

Intravenous Administration of 18F-OP-801 (18F Hydroxyl Dendrimer)

Group III: Healthy Volunteer participants Experimental Treatment 1 Intervention

Intravenous Administration of 18F-OP-801 (18F Hydroxyl Dendrimer)

Group IV: Amyotrophic Lateral Sclerosis participants Experimental Treatment 1 Intervention

Intravenous Administration of 18F-OP-801 (18F Hydroxyl Dendrimer)

Group V: Alzheimer's Disease participants Experimental Treatment 1 Intervention

Intravenous Administration of 18F-OP-801 (18F Hydroxyl Dendrimer)

Who Is Running the Clinical Trial?

Ashvattha Therapeutics, Inc.

Lead Sponsor

Trials

4

Recruited

160+

Findings from Research

Positron emission tomography (PET) imaging shows promise as a biomarker for amyotrophic lateral sclerosis (ALS), allowing visualization of central nervous system pathology and potentially aiding in diagnosis, prognosis, and monitoring treatment effects.

Over 30 years of PET imaging studies have highlighted its ability to detect upper motor neuron pathology in ALS patients, even before symptoms appear, which could enhance patient stratification for clinical trials and improve therapeutic development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positron Emission Tomography Molecular Imaging Biomarkers for Amyotrophic Lateral Sclerosis. Chew, S., Atassi, N.[2020]

A study involving 418 ALS patients demonstrated that brain 2-[18F]FDG-PET can accurately predict survival time ranges, classifying patients into three profiles: 0-2 years, 2-5 years, and over 5 years.

The use of artificial intelligence, specifically a support vector machine, achieved a prediction accuracy with an error rate of less than 20% for two out of three survival classes, highlighting the potential of 2-[18F]FDG-PET as a valuable prognostic tool for managing ALS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of brain 2-[18F]fluoro-2-deoxy-D-glucose-positron-emission tomography as survival predictor in amyotrophic lateral sclerosis. Canosa, A., Martino, A., Manera, U., et al.[2023]

In a study involving 195 patients with amyotrophic lateral sclerosis (ALS) and 40 controls, (18)F-FDG PET imaging revealed significant metabolic changes, including hypometabolism in the frontal and occipital cortex and hypermetabolism in the midbrain, which could serve as a neurobiological marker for ALS.

The discriminant analysis demonstrated a high sensitivity of 95% and specificity of 83% in distinguishing ALS patients from controls, suggesting that (18)F-FDG PET could be a valuable biomarker for ALS diagnosis once further validated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional pattern of brain FDG-PET in amyotrophic lateral sclerosis. Pagani, M., Chiò, A., Valentini, MC., et al.[2022]

The study demonstrated that both 18F-DPA714 and 11C-PBR28 PET imaging can effectively visualize neuroinflammation in ALS patients, with significant increases in tracer uptake observed in the primary motor cortices, indicating glial activation.

By validating a pseudo reference region analysis technique for both tracers, the research supports the feasibility of pooling TSPO PET data across multiple centers, enhancing the potential for these tracers to serve as reliable biomarkers in future ALS clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moving Toward Multicenter Therapeutic Trials in Amyotrophic Lateral Sclerosis: Feasibility of Data Pooling Using Different Translocator Protein PET Radioligands. Van Weehaeghe, D., Babu, S., De Vocht, J., et al.[2022]

In a phase 2 trial (CENTAUR) involving adults with ALS, the coformulation of sodium phenylbutyrate-taurursodiol (PB-TURSO) significantly improved survival, with a median overall survival of 25.0 months compared to 18.5 months for the placebo group.

Participants who started treatment with PB-TURSO at baseline experienced a 6.5-month longer median survival, indicating that PB-TURSO not only slows functional decline but also offers survival benefits for ALS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis. Paganoni, S., Hendrix, S., Dickson, SP., et al.[2022]

The preclinical studies showed that [18F]MK-6240 is safe for use, with no adverse effects observed in rats at doses up to 1000 times the anticipated clinical dose, indicating a strong safety profile for human use.

In human studies, [18F]MK-6240 demonstrated effective biodistribution for brain imaging, with a low effective dose of 5.4 mSv per scan, allowing for multiple imaging sessions per year without significant risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Safety Evaluation and Human Dosimetry of [18F]MK-6240, a Novel PET Tracer for Imaging Neurofibrillary Tangles. Koole, M., Lohith, TG., Valentine, JL., et al.[2021]

The newly developed 18F-OF-NB1 PET probe shows high binding affinity and specificity for GluN2B subunits of the N-methyl-d-aspartate receptor, making it a promising tool for imaging in brain disorders, particularly ALS.

In vivo studies demonstrated that 18F-OF-NB1 effectively differentiates between healthy and ALS-affected brain tissues, indicating its potential for receptor occupancy studies and further research in neurodegenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Development of 18F-OF-NB1 for Imaging GluN2B-Containing N-Methyl-d-Aspartate Receptors and Its Utility as a Biomarker for Amyotrophic Lateral Sclerosis. Ahmed, H., Wallimann, R., Haider, A., et al.[2021]

In a study involving 33 patients with progressive supranuclear palsy (PSP), 18 F-flortaucipir showed significantly elevated uptake in specific brain regions compared to normal controls (46 participants) and patients with Parkinson disease (26 participants), indicating its potential as a biomarker for tau pathology in PSP.

The globus pallidus region was particularly effective in distinguishing PSP patients from both controls and Parkinson disease patients, with high accuracy (AUC values of 0.872 and 0.893, respectively), suggesting that 18 F-flortaucipir could aid in the diagnosis of PSP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18 F-flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: A multicenter study. Schonhaut, DR., McMillan, CT., Spina, S., et al.[2022]

The synthesized PET tracer [18F]cEFQ shows high radiochemical purity and specific activity, making it a promising tool for imaging the metabotropic glutamate receptor type 1 (mGluR1) in the brain, which is linked to various neurological disorders.

In vivo studies demonstrated that [18F]cEFQ has significant brain uptake, particularly in the cerebellum, and its uptake can be specifically blocked by mGluR1 antagonists, confirming its selectivity for mGluR1 over mGluR5.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical anaylses of [18F]cEFQ as a PET tracer for imaging metabotropic glutamate receptor type 1 (mGluR1). Lee, B., Kim, YK., Lee, JY., et al.[2018]

The novel tau imaging agent [18F]N-methyl lansoprazole ([18F]NML) was successfully synthesized and validated for clinical use, showing good radiochemical purity and safety in a study involving 15 participants, with no adverse effects reported.

Despite its high affinity for tau aggregates in laboratory tests, [18F]NML demonstrated low brain retention and lacked specific imaging signals in patients with mild cognitive impairment and Alzheimer's disease, leading to the conclusion that further development of this agent is not justified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of [18F]-N-Methyl lansoprazole as a Tau PET Imaging Agent in First-in-Human Studies. Kramer, V., Brooks, AF., Haeger, A., et al.[2021]

The use of 18F-THK5351 PET imaging effectively visualized lesions associated with astrogliosis in two ALS patients, highlighting its potential as a diagnostic tool for assessing ALS pathophysiology.

In both cases, the elevated uptake of the PET tracer corresponded to specific neurological features of the patients, indicating that this imaging technique can provide insights into the disease's progression and localization of damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-THK5351 PET Can Identify Core Lesions in Different Amyotrophic Lateral Sclerosis Phenotypes. Higashihara, M., Ishibashi, K., Tokumaru, AM., et al.[2023]

In a study involving 17 patients with amyotrophic lateral sclerosis (ALS), impaired fixation of the imaging agent 123I-IMP was observed in the whole brain, indicating potential changes in brain function associated with the disease.

The degree of impaired fixation correlated with the severity of ALS, suggesting that as the disease progresses, brain function may be increasingly affected, regardless of the clinical variant or patient age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-isopropyl-p-123I-amphetamine single photon emission computer tomography in motor neuron disease. Ludolph, AC., Elger, CE., Böttger, IW., et al.[2018]

In a study of 390 ALS patients using 18F-FDG-PET imaging, brain metabolism was found to decrease as the disease progressed through King's stages, particularly in the frontal and motor regions.

The research indicates that neurodegeneration in ALS follows a specific pattern, starting from the motor cortex and spreading to other brain areas, with significant metabolic changes observed between stages 2 and 3.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain metabolic changes across King's stages in amyotrophic lateral sclerosis: a 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography study. Canosa, A., Calvo, A., Moglia, C., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Positron Emission Tomography Molecular Imaging Biomarkers for Amyotrophic Lateral Sclerosis. [2020]

2. Germany pubmed.ncbi.nlm.nih.gov

Role of brain 2-[18F]fluoro-2-deoxy-D-glucose-positron-emission tomography as survival predictor in amyotrophic lateral sclerosis. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Functional pattern of brain FDG-PET in amyotrophic lateral sclerosis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Moving Toward Multicenter Therapeutic Trials in Amyotrophic Lateral Sclerosis: Feasibility of Data Pooling Using Different Translocator Protein PET Radioligands. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Preclinical Safety Evaluation and Human Dosimetry of [18F]MK-6240, a Novel PET Tracer for Imaging Neurofibrillary Tangles. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Preclinical Development of 18F-OF-NB1 for Imaging GluN2B-Containing N-Methyl-d-Aspartate Receptors and Its Utility as a Biomarker for Amyotrophic Lateral Sclerosis. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

18 F-flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: A multicenter study. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Preclinical anaylses of [18F]cEFQ as a PET tracer for imaging metabotropic glutamate receptor type 1 (mGluR1). [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Evaluation of [18F]-N-Methyl lansoprazole as a Tau PET Imaging Agent in First-in-Human Studies. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

18F-THK5351 PET Can Identify Core Lesions in Different Amyotrophic Lateral Sclerosis Phenotypes. [2023]

12. Switzerland pubmed.ncbi.nlm.nih.gov

N-isopropyl-p-123I-amphetamine single photon emission computer tomography in motor neuron disease. [2018]

13. Germany pubmed.ncbi.nlm.nih.gov

Brain metabolic changes across King's stages in amyotrophic lateral sclerosis: a 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography study. [2021]