Study of Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of NIO752 in Early Alzheimer’s Disease Participants

Brief Title

Study of Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of NIO752 in Early Alzheimer's Disease Participants

Official Title

A Randomized, Participant and Investigator Blinded, Placebo-Controlled Study to Evaluate the Ability of a Single Intrathecally Administered Dose of NIO752 to Lower Cerebrospinal Fluid Total Tau Levels in Participants With Early Alzheimer's Disease

Brief Summary

      Phase 1b study to assess the pharmacodynamics, safety, tolerability, and pharmacokinetics of
      NIO752 in patients with early Alzheimer's disease (AD)
    

Detailed Description

      This is a phase 1b, randomized, double-blind, placebo-controlled study, in which patients
      with early AD will receive a single intrathecal dose of NIO752.

      A total of 24 participants will be enrolled into one of two cohorts (each with 12
      participants) and randomized into receiving one dose of NIO752 or placebo in 2:1 ratio.

      Participants will remain in this study for a 170-day follow-up period including approximately
      3 in-clinic visits.

      Cohorts will be enrolled sequentially.

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

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Change in cerebrospinal total tau from baseline to Day 85

Secondary Outcome

 Number of adverse events and serious adverse events

Condition

Alzheimer Disease

Intervention

NIO752

Study Arms / Comparison Groups

 NIO752 - Dose A - Cohort 1
Description:  A single intrathecal injection of 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

24

Start Date

September 9, 2022

Completion Date

November 22, 2023

Primary Completion Date

November 22, 2023

Eligibility Criteria

        Main Inclusion Criteria:

          -  Between 30 to 74 years old (both inclusive) at the time of informed consent.

          -  A diagnosis of mild Alzheimer's Disease (AD) or mild cognitive impairment (MCI) due to
             AD at screening with at least a 6-month decline in cognitive function prior to
             screening documented in the medical record. Both participants with sporadic AD as well
             as Amyloid Precursor Protein (APP), Presenilin-1 (PSEN1) or Presenilin-2 (PSEN2)
             mutation carriers are eligible.

          -  Participants must have a diagnosis of MCI due to AD or mild AD at screening as defined
             by a Clinical Dementia Rating Scale (CDR) Global Score of 0.5 or 1 and a Memory Score
             ≥ 0.5.

          -  A history of CSF biomarkers supporting the diagnosis of AD obtained at any time prior
             to screening, including CSF amyloid (Aβ42 and/or Aβ42/40 ratio) and tau species (total
             tau and/or phosphorylated tau).

          -  Participant has a reliable study partner or caregiver (e.g., spouse, sibling, close
             friend, adult child) who, is at least 18 years old.

          -  Participant resides in a proximity to the study site to allow a timely unscheduled
             visit in the study site, if necessary.

          -  Participant is able to undergo lumbar puncture (LP), CSF collections, and blood draws,
             tolerate brain MRI, and able to participate and tolerate all study procedures at study
             visit.

        Main Exclusion Criteria:

          -  Participant lives in a skilled nursing facility or dementia care facility.

          -  Any previous use of experimental therapy within 180 days or 5 half-lives prior to Day
             1, whichever is greater. Previous exposure to anti-tau and anti-β-amyloid antibodies
             is allowed if at the time of screening at least 180 days have passed since the last
             dose. Previous exposure to amyloid vaccines or tau vaccines meant to treat AD, or
             previous treatment with oligonucleotides or with gene therapy at any time frame is not
             allowed.

          -  Any current or past non-AD neurological conditions.

          -  Other medical conditions including but not limited to poorly controlled diabetes
             mellitus, unstable angina, myocardial infarction, chronic heart failure, clinical
             significant conduction abnormalities, impaired renal or kidney function, which, in the
             opinion of the Investigator, would make the participant unsuitable for inclusion or
             could interfere with the participation in or completion of the study.

          -  Treatment with immunosuppressants, antipsychotics, lithium, neuroleptics, dopaminergic
             agonists, L-dopa, or monoamine oxidase inhibitors at the time of screening. Current
             use of medications, other than cholinesterase inhibitors and/or memantine, that could
             alter cognition, as determined by the Investigator. If the participant is receiving
             cholinesterase inhibitors and/or memantine, the dose must have been stable within 12
             weeks prior to screening, and must remain stable during the duration of the study.

          -  Brain MRI at screening or within 12 months prior to screening showing evidence of
             cerebrovascular disease such as acute or sub-acute micro- or macrohemorrhage,
             significant signs of major cerebrovascular disease, or any other imaging evidence
             that, in the opinion of the Investigator, makes the participant unsuitable for the
             study.
      

Gender

All

Ages

30 Years - 74 Years

Accepts Healthy Volunteers

No

Contacts

Jose-Alberto Palma, MD PhD, +41613241111, [email protected]



Administrative Informations


NCT ID

NCT05469360

Organization ID

CNIO752B12201

Secondary IDs

2022-000921-26

Responsible Party

Sponsor

Study Sponsor

Novartis Pharmaceuticals


Study Sponsor

Jose-Alberto Palma, MD PhD, Study Director, Novartis Pharmaceuticals


Verification Date

July 2022