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.
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.
12345What 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.
678910Is 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.
34111213Eligibility 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.
+33 more
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
+23 more
Participant Groups
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.
5Treatment groups
Experimental Treatment
Group I: Parkinson's Disease participantsExperimental Treatment1 Intervention
Intravenous Administration of 18F-OP-801 (18F Hydroxyl Dendrimer)
Group II: Multiple Sclerosis participantsExperimental Treatment1 Intervention
Intravenous Administration of 18F-OP-801 (18F Hydroxyl Dendrimer)
Group III: Healthy Volunteer participantsExperimental Treatment1 Intervention
Intravenous Administration of 18F-OP-801 (18F Hydroxyl Dendrimer)
Group IV: Amyotrophic Lateral Sclerosis participantsExperimental Treatment1 Intervention
Intravenous Administration of 18F-OP-801 (18F Hydroxyl Dendrimer)
Group V: Alzheimer's Disease participantsExperimental Treatment1 Intervention
Intravenous Administration of 18F-OP-801 (18F Hydroxyl Dendrimer)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Stanford UniversityStanford, CA
UCSFSan Francisco, CA
Mayo Clinic JacksonvilleJacksonville, FL
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Who Is Running the Clinical Trial?
Ashvattha Therapeutics, Inc.Lead Sponsor
References
Positron Emission Tomography Molecular Imaging Biomarkers for Amyotrophic Lateral Sclerosis. [2020]Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with limited treatment options. Despite decades of therapeutic development, only two modestly efficacious disease-modifying drugs-riluzole and edaravone-are available to ALS patients. Biomarkers that can facilitate ALS diagnosis, aid in prognosis, and measure drug pharmacodynamics are needed to accelerate therapeutic development for patients with ALS. Positron emission tomography (PET) imaging has promise as a biomarker for ALS because it permits visualization of central nervous system (CNS) pathology in individuals living with ALS. The availability of PET radioligands that target a variety of potential pathophysiological mechanisms-including cerebral metabolism, neuroinflammation, neuronal dysfunction, and oxidative stress-has enabled dynamic interrogation of molecular changes in ALS, in both natural history studies and human clinical trials. PET imaging has potential as a diagnostic biomarker that can establish upper motor neuron (UMN) pathology in ALS patients without overt UMN symptoms, as a prognostic biomarker that might help stratify patients for clinical trials, and as a pharmacodynamic biomarker that measures the biological effect of investigational drugs in the brain and spinal cord. In this Review, we discuss progress made with 30 years of PET imaging studies in ALS and consider future research needed to establish PET imaging biomarkers for ALS therapeutic development.
Role of brain 2-[18F]fluoro-2-deoxy-D-glucose-positron-emission tomography as survival predictor in amyotrophic lateral sclerosis. [2023]Label="PURPOSE">The identification of prognostic tools in amyotrophic lateral sclerosis (ALS) would improve the design of clinical trials, the management of patients, and life planning. We aimed to evaluate the accuracy of brain 2-[18F]fluoro-2-deoxy-D-glucose-positron-emission tomography (2-[18F]FDG-PET) as an independent predictor of survival in ALS.
Functional pattern of brain FDG-PET in amyotrophic lateral sclerosis. [2022]We investigated a large sample of patients with amyotrophic lateral sclerosis (ALS) at rest in order to assess the value of (18)F-2-fluoro-2-deoxy-d-glucose ((18)F-FDG) PET as a biomarker to discriminate patients from controls.
Moving Toward Multicenter Therapeutic Trials in Amyotrophic Lateral Sclerosis: Feasibility of Data Pooling Using Different Translocator Protein PET Radioligands. [2022]Neuroinflammation has been implicated in amyotrophic lateral sclerosis (ALS) and can be visualized using translocator protein (TSPO) radioligands. To become a reliable pharmacodynamic biomarker for ALS multicenter trials, TSPO radioligands have some challenges to overcome. We aimed to investigate whether multicenter data pooling of different TSPO tracers (11C-PBR28 and 18F-DPA714) is feasible, after validation of an established 11C-PBR28 PET pseudo reference analysis technique for 18F-DPA714. Methods: Seven ALS patients from Belgium (58.9 ± 6.7 y old, 5 men and 2 women), 8 healthy volunteers from Belgium (52.1 ± 15.2 y old, 3 men and 5 women), 7 ALS patients from the United States (53.4 ± 9.8 y old, 5 men and 2 women), and 7 healthy volunteers from the United States (54.6 ± 9.6 y old, 4 men and 3 women) from a previously published study underwent dynamic 18F-DPA714 (Leuven, Belgium) or 11C-PBR28 (Boston, Massachusetts) PET/MRI. For 18F-DPA714, maps of total volume of distribution (VT) were compared with SUV ratio (SUVR) images from 40 to 60 min after injection (SUVR40-60) calculated using the pseudo reference regions cerebellum, occipital cortex, and whole brain (WB) without ventricles. For 11C-PBR28, SUVR images from 60 to 90 min after injection using the WB without ventricles were calculated. Results: In line with previous studies, increased 18F-DPA714 uptake (17.0% ± 5.6%) in primary motor cortices was observed in ALS subjects, as measured by both VT and SUVR40-60 approaches. The highest sensitivity was found for SUVR calculated using the WB without ventricles (average cluster, 21.6% ± 0.1%). 18F-DPA714 VT ratio was highly correlated with the SUVR40-60 (r > 0.8, P < 0.001). A similar pattern of increased uptake (average cluster, 20.5% ± 0.5%) in the primary motor cortices was observed in ALS subjects for 11C-PBR28 SUVR calculated using the WB without ventricles. Analysis of the 18F-DPA714 and 11C-PBR28 data together resulted in a more extensive pattern of significantly increased glial activation bilaterally in the primary motor cortices. Conclusion: The same pseudo reference region analysis technique for 11C-PBR28 PET can be extended toward 18F-DPA714 PET. Therefore, in ALS, standardized analysis across these 2 tracers enables pooling of TSPO PET data across multiple centers and increases the power of TSPO as a biomarker for future therapeutic trials.
Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis. [2022]An orally administered, fixed-dose coformulation of sodium phenylbutyrate-taurursodiol (PB-TURSO) significantly slowed functional decline in a randomized, placebo-controlled, phase 2 trial in ALS (CENTAUR). Herein we report results of a long-term survival analysis of participants in CENTAUR. In CENTAUR, adults with ALS were randomized 2:1 to PB-TURSO or placebo. Participants completing the 6-month (24-week) randomized phase were eligible to receive PB-TURSO in the open-label extension. An all-cause mortality analysis (35-month maximum follow-up post-randomization) incorporated all randomized participants. Participants and site investigators were blinded to treatment assignments through the duration of follow-up of this analysis. Vital status was obtained for 135 of 137 participants originally randomized in CENTAUR. Median overall survival was 25.0 months among participants originally randomized to PB-TURSO and 18.5 months among those originally randomized to placebo (hazard ratio, 0.56; 95% confidence interval, 0.34-0.92; P = .023). Initiation of PB-TURSO treatment at baseline resulted in a 6.5-month longer median survival as compared with placebo. Combined with results from CENTAUR, these results suggest that PB-TURSO has both functional and survival benefits in ALS.
Preclinical Safety Evaluation and Human Dosimetry of [18F]MK-6240, a Novel PET Tracer for Imaging Neurofibrillary Tangles. [2021]Label="PURPOSE">[18F]MK-6240 is a selective, high-affinity positron emission tomography tracer for imaging neurofibrillary tangles, a key pathological signature that correlates with cognitive decline in Alzheimer disease. This report provides safety information from preclinical toxicology studies and first-in-human whole-body biodistribution and dosimetry studies of [18F]MK-6240 for its potential application in human brain imaging studies.
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]As part of our continuous efforts to develop a suitable 18F-labeled PET radioligand with improved characteristics for imaging the N-methyl-d-aspartate receptors (NMDARs) subtype 2B (GluN1/2B), we investigated in the current work ortho-fluorinated (OF) and meta-fluorinated (MF) analogs of 18F-para-fluorinated (PF)-NB1, a 3-benzazepine-based radiofluorinated probe. Methods: OF-NB1 and MF-NB1 were prepared using a multistep synthesis, and their binding affinities toward GluN2B subunits and selectivity over σ1 receptors (σ1Rs) were determined via competitive binding assays. 18F-OF-NB1 was synthesized via copper-mediated radiofluorination and was evaluated in Wistar rats by in vitro autoradiography, PET imaging, ex vivo biodistribution, metabolite experiments, and receptor occupancy studies using CP-101,606, an established GluN2B antagonist. To determine in vivo selectivity, 18F-OF-NB1 was validated in wild-type and σ1R knock-out mice. Translational relevance was assessed in autoradiographic studies using postmortem human brain tissues from healthy individuals and ALS patients, the results of which were corroborated by immunohistochemistry. Results: The binding affinity values for OF-NB1 and MF-NB1 toward the GluN2B subunits were 10.4 ± 4.7 and 590 ± 36 nM, respectively. For σ1R binding, OF-NB1 and MF-NB1 exhibited inhibition constants of 410 and 2,700 nM, respectively. OF-NB1, which outperformed MF-NB1, was radiolabeled with 18F to afford 18F-OF-NB1 in more than 95% radiochemical purity and molar activities of 192 ± 33 GBq/μmol. In autoradiography experiments, 18F-OF-NB1 displayed a heterogeneous and specific binding in GluN2B subunit-rich brain regions such as the cortex, striatum, hypothalamus, and hippocampus. PET imaging studies in Wistar rats showed a similar heterogeneous uptake, and no brain radiometabolites were detected. A dose-dependent blocking effect was observed with CP-101,606 (0.5-15 mg/kg) and resulted in a 50% receptor occupancy of 8.1 μmol/kg. Postmortem autoradiography results revealed lower expression of the GluN2B subunits in ALS brain tissue sections than in healthy controls, in line with immunohistochemistry results. Conclusion:18F-OF-NB1 is a highly promising PET probe for imaging the GluN2B subunits of the N-methyl-d-aspartate receptor. It possesses utility for receptor occupancy studies and has potential for PET imaging studies in ALS patients and possibly other brain disorders.
18 F-flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: A multicenter study. [2022]Label="OBJECTIVE" NlmCategory="OBJECTIVE"> 18 F-flortaucipir (formerly 18 F-AV1451 or 18 F-T807) binds to neurofibrillary tangles in Alzheimer disease, but tissue studies assessing binding to tau aggregates in progressive supranuclear palsy (PSP) have yielded mixed results. We compared in vivo 18 F-flortaucipir uptake in patients meeting clinical research criteria for PSP (n = 33) to normal controls (n = 46) and patients meeting criteria for Parkinson disease (PD; n = 26).
Preclinical anaylses of [18F]cEFQ as a PET tracer for imaging metabotropic glutamate receptor type 1 (mGluR1). [2018]Metabotropic glutamate receptor type 1 (mGluR1) is related with various neurological and psychiatric diseases, such as anxiety, depression, epilepsy, Parkinson's disease, and neuropathic pain. Hence, mGluR1 is an important target for drug development and imaging. We synthesized [18F]cEFQ (3-ethyl-2-[18F]fluoroquinolin-6-yl cis-(4-methoxycyclohexyl)methanone) as a PET tracer for selective mGluR1 imaging and evaluated its properties in rodents. A chloroquinoline precursor was labeled by a nucleophilic substitution reaction, and the resulting [18F]cEFQ was obtained with high radiochemical purity (>99%) and specific activity (63-246 GBq/µmol). The log D value was 3.24, and the initial brain uptake at 10 min was over 4% of injected dose per gram in BALB/c mice. According to PET/CT and autoradiography in SD rats, [18F]cEFQ showed wide distribution in the whole brain and the highest uptake in the cerebellum. Pre-treatment with unlabeled cEFQ or the mGluR1-specific antagonist JNJ16259685 blocked the uptake of [18F]cEFQ. However, the uptake was not blocked by pre-treatment with the mGluR5-specific antagonist ABP688. The trans isomer [18F]tEFQ did not show high uptake in the mGluR1-rich region. [18F]cEFQ was straightforwardly prepared using a chloro-derivative precursor. Its feasibility as a specific and selective PET agent for imaging mGluR1 was proved by in vitro and in vivo experiments using rodents.
Evaluation of [18F]-N-Methyl lansoprazole as a Tau PET Imaging Agent in First-in-Human Studies. [2021]Development of positron emission tomography (PET) imaging agents capable of quantifying tau aggregates in neurodegenerative disorders such as Alzheimer's disease (AD) is of enormous importance in the field of dementia research. The aim of the present study was to conduct first-in-man imaging studies with the potential novel tau imaging agent [18F]N-methyl lansoprazole ([18F]NML). Herein we report validation of the synthesis of [18F]NML for clinical use by labeling the trifluoromethyl group via radiofluorination of the corresponding gem-difluoro enol ether precursor. This is the first use of this method for clinical production of PET radiotracers and confirmed that it can be readily implemented at multiple production facilities to provide [18F]NML in good noncorrected radiochemical yield (3.4 ± 1.5 GBq, 4.6% ± 2.6%) and molar activity (120.1 ± 186.3 GBq/μmol), excellent radiochemical purity (>97%), and suitable for human use (n = 15). With [18F]NML in hand, we conducted rodent biodistribution, estimates of human dosimetry, and preliminary evaluation of [18F]NML in human subjects at two imaging sites. Healthy controls (n = 4) and mildly cognitively impaired (MCI) AD patients (n = 6) received [18F]NML (tau), [18F]AV1451 (tau), and [18F]florbetaben or [18F]florbetapir (amyloid) PET scans. A single progressive supranuclear palsy (PSP) patient also received [18F]NML and [18F]AV1451 PET scans. [18F]NML showed good brain uptake, reasonable pharmacokinetics, and appropriate imaging characteristics in healthy controls. The mean ± SD of the administered mass of [18F/19F]NML was 2.01 ± 2.17 μg (range, 0.16-8.27 μg) and the mean administered activity was 350 ± 62 MBq (range, 199-403 MBq). There were no adverse or clinically detectable pharmacologic effects in any of the 11 subjects, and no significant changes in vital signs were observed. However, despite high affinity for tau in vitro, brain retention in MCI/AD and PSP patients was low, and there was no evidence of specific signals in vivo that corresponded to tau. Although it is still unclear why clinical translation of the radiotracer was unsuccessful, we nevertheless conclude that further development of [18F]NML as a tau PET imaging agent is not warranted at this time.
18F-THK5351 PET Can Identify Core Lesions in Different Amyotrophic Lateral Sclerosis Phenotypes. [2023]Two patients with different amyotrophic lateral sclerosis (ALS) phenotypes underwent 18F-THK5351 PET to visualize lesions undergoing astrogliosis by measuring monoamine oxidase B activity. Patient 1 was a 57-year-old man with flail leg syndrome. Elevated uptake was observed inside the motor cortex, corresponding to the leg area in a cortical homunculus. Patient 2 was a 64-year-old man with ALS-frontotemporal dementia semantic variant. Elevated uptake was observed around the left anterior temporal lobe. Both core lesions were consistent with their respective neurological features. Hence, 18F-THK5351 PET is a useful technique to assess ALS pathophysiology by visualizing the core lesions.
N-isopropyl-p-123I-amphetamine single photon emission computer tomography in motor neuron disease. [2018]N-Isopropyl-p-123I-amphetamine (123I-IMP) single photon emission computer tomography studies were performed on 17 patients suffering from amyotrophic lateral sclerosis (ALS). All patients displayed varying degrees of impaired fixation of 123I-IMP in the whole brain. These findings were not related to the clinical variants of ALS and the age of the patients. A correlation between the severity of the disease and the degree of impaired fixation could be observed. In addition, patients suffering from ALS for longer periods showed more pronounced impairment of 123I-IMP fixation.
Brain metabolic changes across King's stages in amyotrophic lateral sclerosis: a 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography study. [2021]Label="PURPOSE">To assess the brain metabolic correlates of the different regional extent of ALS, evaluated with the King's staging system, using brain 18F-2-fluoro-2-deoxy-D-glucose-PET (18F-FDG-PET).