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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new tool called 18F-OP-801, which helps doctors detect brain inflammation using PET scans. It aims to determine if 18F-OP-801 is safe and effective for imaging inflammation in individuals with diseases like ALS, Alzheimer's, MS, and Parkinson's. People with these conditions, who have stable symptoms but face challenges like difficulty breathing or memory issues, might be suitable for this study. Participants will receive 18F-OP-801 through an IV, and researchers will use it to enhance understanding of how these neurological diseases affect the brain. As a Phase 1, Phase 2 trial, this study focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

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.

Is there any evidence suggesting that 18F-OP-801 is likely to be safe for humans?

Research shows that 18F-OP-801 is a promising new treatment being tested for its safety and ability to reduce brain inflammation. Studies have found that this treatment can reach the brain, which is crucial for treating diseases like ALS, Alzheimer's, Parkinson's, and Multiple Sclerosis.

Available research suggests that 18F-OP-801 is generally well-tolerated, with most people not experiencing serious side effects. It is used in PET scans to help doctors see brain activity and inflammation.

However, since the current study is in the early stages (Phase 1/2), researchers are still learning about its full safety profile. This phase mainly focuses on assessing the treatment's safety and behavior in the body. It is an important step to ensure 18F-OP-801 is safe for broader use.

Overall, the initial results are positive, but more information from ongoing studies will provide a clearer understanding of its safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard ALS treatments, which often focus on managing symptoms or slowing progression through medications like Riluzole and Edaravone, 18F-OP-801 offers a novel approach. This treatment utilizes a hydroxyl dendrimer, a unique structure that enhances drug delivery directly to affected cells. Researchers are excited because this targeted delivery system might improve treatment effectiveness by focusing on the disease's root causes rather than just alleviating symptoms. This new mechanism of action holds promise for more significant improvements in patient outcomes.

What evidence suggests that 18F-OP-801 could be an effective biomarker for neuroinflammation in ALS?

Research shows that 18F-OP-801 is a promising tool for imaging. It targets specific cells called reactive microglia and macrophages, which play a role in brain inflammation—a key feature in diseases like ALS (Amyotrophic Lateral Sclerosis). In this trial, participants with ALS, as well as those with conditions like Multiple Sclerosis, Alzheimer's Disease, and Parkinson's Disease, will receive 18F-OP-801 to assess its imaging capabilities. Early results suggest that this imaging agent effectively highlights areas of brain inflammation using PET scans. This helps researchers understand disease progression and treatment response. While more research is needed to confirm its effectiveness in treating ALS, its ability to show inflammation marks an important first step. ^{1 2 3 6 7}

Who Is on the Research Team?

Farshad Moradi, MD, PhD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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

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

I have not taken corticosteroids in the last 30 days.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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]

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 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 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 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]

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]

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]

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]

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]

Citations

1. neals.org neals.org/als-trials/nct05395624

A Phase 1/2 Study to Evaluate the Safety, ... A Phase 1/2 study to evaluate the safety, pharmacokinetics and biodistribution of an imaging agent, 18F-OP-801 (18F Hydroxyl Dendrimer), after intravenous ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05395624

NCT05395624 | Safety, PK and Biodistribution of 18F-OP ... This is a Phase 1/2 study to evaluate the safety and tolerability of 18F-OP-801 in subjects with ALS, AD, MS, PD and age-matched HVs. 18F-OP-801 is intended ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10326869/

Clinical Radiosynthesis and Translation of [18F]OP-801 We recently reported a promising dendrimer PET tracer ([ 18 F]OP-801), which is selectively taken up by reactive microglia and macrophages.

4. avttx.com avttx.com/ashvattha-therapeutics-announces-preclinical-data-at-the-2022-alzheimers-association-international-conference-aaic-demonstrating-its-hydroxyl-dendrimer-based-imaging-agent-18fop-801-can-d/

Ashvattha Therapeutics Data highlights [18F]OP-801's differentiated imaging profile as a promising tracer for visualizing the progression of neuroinflammation –.

5. mayo.edu mayo.edu/research/clinical-trials/diseases-conditions/amyotrophic-lateral-sclerosis-(als)

Amyotrophic Lateral Sclerosis (ALS) Clinical Trials The purpose of this study is to assess the effect of Reldesemtiv versus placebo on functional outcomes in Amyotrophic Lateral Sclerosis (ALS). ... 18F-OP-801 (18F ...

6. mayo.edu mayo.edu/research/clinical-trials/cls-20543804

Clinical Trials About this study. The purpose of this study is to evaluate the safety, pharmacokinetics and biodistribution of an imaging agent, 18F-OP-801 ...

7. avttx.com avttx.com/ashvattha-therapeutics-announces-first-patient-enrolled-in-a-phase-1-study-of-18fop-801-for-use-as-imaging-agent/

Ashvattha Therapeutics Announces First Patient Enrolled ... The study will evaluate the safety, tolerability and ability of [ 18 F]OP-801 to cross the blood brain barrier and selectively target neuroinflammation.