A Study of the Safety, Tolerability, and Drug/Body Interactions of C2N-8E12 in People with Progressive Supranuclear Palsy

Overview

About this study

The purpose of this study is to evaluate the safety, tolerability and drug/body interactions of C2N-8E12 in patients with progressive supranuclear palsy.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

Inclusion Criteria 

  • Meets NINDS-SPSP possible or probable criteria as modified for NNIPPS and AL-108-231 clinical trials
  • Brain MRI at screening is consistent with Progressive Supranuclear Palsy
  • Stable medications for Parkinsonism for at least 2 months prior to screening
  • Agree to use protocol specified methods of contraception

Exclusion Criteria

  • Signs of a progressive neurological disorder that better meets the criteria for types of neurological disorders other than PSP
  • Currently on any other biologic or immunomodulatory therapy
  • Subjects that reside at a skilled nursing or dementia care facility
  • Diagnosis of any other significant unrelated neurological or psychiatric disorders that could account for cognitive deficits
  • Untreated major depression at baseline evaluation, based on clinical judgment and results in geriatric depression scale
  • Unable to tolerate MRI scan at screening or any other contraindication to MRI
  • Any contraindication to or unable to tolerate lumbar puncture at screening, including use of anti-coagulant medications

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

Bradley Boeve, M.D.

Closed for enrollment

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Bradley Boeve, M.D.

Closed for enrollment

Jacksonville, Fla.

Mayo Clinic principal investigator

Bradley Boeve, M.D.

Closed for enrollment

More information

Publications

  • We previously found a strong reduction in tau pathology and insoluble tau in P301S tau transgenic mice following intracerebroventricular infusion of the anti-tau antibody HJ8.5. We sought to determine the effects of HJ8.5 in the same model following peripheral administration. Read More on PubMed
  • In preclinical studies, davunetide promoted microtubule stability and reduced tau phosphorylation. Because progressive supranuclear palsy (PSP) is linked to tau pathology, davunetide could be a treatment for PSP. We assessed the safety and efficacy of davunetide in patients with PSP. Read More on PubMed
  • Tau aggregation occurs in neurodegenerative diseases including Alzheimer's disease and many other disorders collectively termed tauopathies. trans-cellular propagation of tau pathology, mediated by extracellular tau aggregates, may underlie pathogenesis of these conditions. P301S tau transgenic mice express mutant human tau protein and develop progressive tau pathology. Using a cell-based biosensor assay, we screened anti-tau monoclonal antibodies for their ability to block seeding activity present in P301S brain lysates. We infused three effective antibodies or controls into the lateral ventricle of P301S mice for 3 months. The antibodies markedly reduced hyperphosphorylated, aggregated, and insoluble tau. They also blocked development of tau seeding activity detected in brain lysates using the biosensor assay, reduced microglial activation, and improved cognitive deficits. These data imply a central role for extracellular tau aggregates in the development of pathology. They also suggest that immunotherapy specifically designed to block trans-cellular aggregate propagation will be a productive treatment strategy. Read More on PubMed
  • To improve the specificity and sensitivity of the clinical diagnosis of progressive supranuclear palsy (PSP, Steele-Richardson-Olszewski syndrome), the National Institute of Neurological Disorders and Stroke (NINDS) and the Society for PSP, Inc. (SPSP) sponsored an international workshop to develop an accurate and universally accepted set of criteria for this disorder. The NINDS-SPSP criteria, which were formulated from an extensive review of the literature, comparison with other previously published sets of criteria, and the consensus of experts, were validated on a clinical data set from autopsy-confirmed cases of PSP. The criteria specify three degrees of diagnostic certainty: possible PSP, probable PSP, and definite PSP. Possible PSP requires the presence of a gradually progressive disorder with onset at age 40 or later, either vertical supranuclear gaze palsy or both slowing of vertical saccades and prominent postural instability with falls in the first year of onset, as well as no evidence of other diseases that could explain these features. Probable PSP requires vertical supranuclear gaze palsy, prominent postural instability, and falls in the first year of onset, as well as the other features of possible PSP. Definite PSP requires a history of probable or possible PSP and histopathologic evidence of typical PSP. Criteria that support the diagnosis of PSP, and that exclude diseases often confused with PSP, are presented. The criteria for probable PSP are highly specific, making them suitable for therapeutic, analytic epidemiologic, and biologic studies, but not very sensitive. The criteria for possible PSP are substantially sensitive, making them suitable for descriptive epidemiologic studies, but less specific. An appendix provides guidelines for diagnosing and monitoring clinical disability in PSP. Read More on PubMed

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

.
CLS-20198649

Mayo Clinic Footer