Safety, Tolerability and Pharmacokinetics of Multiple Ascending Doses of NIO752 in Progressive Supranuclear Palsy

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Brief Title

Safety, Tolerability and Pharmacokinetics of Multiple Ascending Doses of NIO752 in Progressive Supranuclear Palsy

Official Title

A Randomized, Participant, Investigator and Sponsor Blinded, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Multiple Ascending Doses of Intrathecally Administered NIO752 in Participants With Progressive Supranuclear Palsy

Brief Summary

      This is a phase 1, multi-center, double-blind, placebo-controlled, multiple dose escalation
      study with NIO752 in progressive supranuclear palsy (PSP) participants.
    

Detailed Description

      This is a phase 1, multi-center, double-blind, placebo-controlled, multiple dose escalation
      study with NIO752 in progressive supranuclear palsy (PSP) participants.

      Approximately 64 PSP participants in 6 cohorts will be randomized to receive NIO752 or
      placebo in a ratio of 3:1. Intrathecal ( IT ) injections of NIO752 or placebo will be given 4
      times over 3 months. All participants will remain in this study for an additional 9 month
      follow-up period with 6 scheduled visits.

      Cohorts will be enrolled sequentially.

      Safety assessments will include physical and neurological examinations, ECGs, vital signs,
      standard clinical laboratory evaluations (hematology, blood chemistry, and urinalysis), CSF
      laboratory test, adverse event, and serious adverse event monitoring.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Number of adverse events and serious adverse events

Secondary Outcome

 Concentrations of NIO752 in blood plasma

Condition

Progressive Supranuclear Palsy (PSP)

Intervention

antisense oligonucleotide

Study Arms / Comparison Groups

 Cohort A NIO752
Description:  4 injections of NIO752 at dose A

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

66

Start Date

February 16, 2021

Completion Date

January 16, 2025

Primary Completion Date

October 17, 2023

Eligibility Criteria

        Inclusion Criteria:

          1. Signed informed consent

          2. Between 40 to 75 years old (inclusive)

          3. Have PSP diagnosed for less than 5 years with a current classification of probable PSP
             Richardson syndrome, a progressive supranuclear palsy rating scale (PSPRS) score < 40
             and MOCA score >17 at screening

          4. Be able to ambulate independently or able to take at least 5 steps with minimal
             assistance

          5. At least a 12-month history of postural instability or falls within 3 years from
             disease onset as per medical history

          6. Vertical supranuclear gaze palsy, or reduced velocity of vertical saccade

          7. Able and willing to meet all study requirements including:

             Have a study partner who is reliable, competent, and at least 18 years of age, and
             will be able to accompany the participant to study visits, be knowledgeable of the
             participant's ongoing condition during the study to provide study related information
             to study site when required both in person and via a phone Reside in a proximity to
             the study site to allow a timely unscheduled visit if necessary (ideally less than 2
             hours) Able to undergo lumbar puncture (LP), CSF draws and blood draws

          8. If the participant is receiving levodopa/carbidopa, levodopa/benserazide, a dopamine
             agonist, catechol-o-methyltransferase (COMT) inhibitor, rasagiline, CoQ10 or other
             Parkinson's medications, acetylcholinesterase inhibitors, antipsychotics, memantine,
             or other non-tau modifying Alzheimer's medication the dose must have been stable for
             at least 30 days prior to the screening visit and must remain stable for the duration
             of the study. No such medication can be initiated during the study.

        Exclusion Criteria:

          1. Live in a skilled nursing facility or dementia care facility

          2. Evidence of motor neuron disease, or any other neurological disease that could explain
             symptoms

          3. Clinically significant laboratory abnormality

          4. Attempted suicide, suicidal ideation with a plan that required hospital admission
             within 12 months prior to Screening. In addition, patients deemed by the Investigator
             to be at significant risk of suicide, major depressive episode, psychosis, confusion
             state, or violent behavior should be excluded.

          5. A clear and robust benefit from levodopa by history

          6. Use of lithium, methylene blue or other putative disease modifying drugs for PSP
             within 30 days of screening

          7. Any previous use of experimental therapy within 30 days or 5 half-lives prior to Day
             1, whichever is greater

          8. Any condition that increases risk of meningitis unless participant is receiving
             appropriate prophylactic treatment

          9. History of post-lumbar-puncture headache of moderate or severe intensity and/or blood
             patch

        11. Hospitalization for any major medical or surgical procedure involving general
        anesthesia within 12 weeks of Screening or planned during the study 12. Unable to undergo
        magnetic resonance imaging (MRI) due to for example claustrophobia, or presents absolute
        contraindications to MRI (e.g., metallic implants, metallic foreign bodies, pacemaker,
        defibrillator) 13. Patients with other significant brain MRI abnormalities by history or at
        screening.
      

Gender

All

Ages

40 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

, 1-888-669-6682, [email protected]

Location Countries

Canada

Location Countries

Canada

Administrative Informations


NCT ID

NCT04539041

Organization ID

CNIO752A02101


Responsible Party

Sponsor

Study Sponsor

Novartis Pharmaceuticals


Study Sponsor

, , 


Verification Date

August 2021