Assessing the safety and effects of NIO752 in early Alzheimer's disease

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

This study is testing a new drug called NIO752 to see if it is safe and effective for people with early Alzheimer's disease or mild cognitive impairment.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 30 Years to 74 Years
• Sex: All
• Sponsor: Novartis (Industry-sponsored)
• Locations: 10 sites (Kuopio and 9 other locations)
• Trial ID: NCT05469360 on ClinicalTrials.gov

What this trial studies

This phase 1b study evaluates the safety, tolerability, pharmacodynamics, and pharmacokinetics of NIO752 in patients diagnosed with early Alzheimer's disease or mild cognitive impairment. A total of 36 participants will be randomized into three cohorts, receiving either NIO752 or a placebo through intrathecal administration. The study includes a placebo-controlled phase followed by an open-label extension, allowing participants to receive NIO752 regardless of their initial treatment assignment. Participants will undergo extensive clinical assessments over approximately 19 months.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 30 to 74 with a diagnosis of mild Alzheimer's disease or mild cognitive impairment due to Alzheimer's.

Not a fit: Patients with advanced Alzheimer's disease or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to a new treatment option for patients with early Alzheimer's disease, potentially slowing disease progression.

How similar studies have performed: While there have been studies on similar pharmacological approaches, this specific intervention is novel and has not been extensively tested in this context.

Eligibility criteria

Main Inclusion Criteria (placebo-controlled part):

* 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 point prior to screening, including CSF amyloid (amyloid-β 42 and/or 42/40 ratio) AND tau species (total tau and/or phosphorylated tau). All participants must have documented historical confirmation of both CSF biomarkers (amyloid-β and tau species) with results supporting a diagnosis of AD prior to screening. This criterion will be determined individually for each participant taking into consideration the biomarker assay used in each case. For participants (Cohorts 1 \& 2 only) with no historical CSF biomarker information, a LP for CSF collection must be performed at the screening visit. For CSF collected at screening, participants must have confirmed positivity of amyloid-β-42 ≤ 1000 pg/mL as well as positivity on, at least, one of the following Tau biomarkers: phosphorylated-tau-181 \> 12 pg/ml OR T-tau \> 149.9 pg/mL as determined by the central laboratory.
* 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 to the study site, if necessary.
* Participant is able to undergo lumbar puncture (LP), CSF collections, and blood draws, tolerate brain MRI and PET scanning, and able to participate and tolerate all study procedures at study visit.

Main Inclusion Criteria (OLE part):

* Signed informed consent of protocol version inclusive of the OLE.
* Participant must complete Day 170 of the placebo-controlled part of this study.

Main Exclusion Criteria (placebo-controlled part):

* 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.

Main Exclusion Criteria (OLE part):

* Use of any investigational drugs, or participation in a clinical trial with an investigational new drug (other than NIO752), after completing the initial placebo-controlled part of this trial
* Participants who withdrew informed consent while participating in the main placebo-controlled part of the study

Where this trial is running

Kuopio and 9 other locations

• Novartis Investigative Site — Kuopio, Finland (Completed)
• Novartis Investigative Site — Turku, Finland (Completed)
• Novartis Investigative Site — Lille, France (Recruiting)
• Novartis Investigative Site — Paris, France (Recruiting)
• Novartis Investigative Site — Toulouse, France (Recruiting)
• Novartis Investigative Site — Valencia, Valencia, Spain (Recruiting)
• Novartis Investigative Site — Barcelona, Spain (Recruiting)
• Novartis Investigative Site — Barcelona, Spain (Recruiting)
• Novartis Investigative Site — Malmö, Sweden (Completed)
• Novartis Investigative Site — Stockholm, Sweden (Completed)

Study contacts

• Study coordinator: Novartis Pharmaceuticals

Conditions Alzheimer Disease; Mild Cognitive Impairment; Autosomal dominant Alzheimer disease; Early onset Alzheimer disease; Familial Alzheimer disease; Dementia; Brain Diseases; Central Nervous System Diseases