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

NCT05469360 | Recruiting Phase 1

• 2 other identifiers: CNIO752B122012024-514004-14
• Study Type: interventional
• Target: 36
• Locations: 4 countries
• Sites: 10

Brief Summary

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

Conditions

Alzheimer Disease; Mild Cognitive Impairment

Keywords

Alzheimer Disease; Autosomal dominant Alzheimer disease; Early onset Alzheimer disease; Familial Alzheimer disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Memory loss; Placebo; Adult

Outcome Measures

Primary Outcomes (1)

• Change in cerebrospinal total tau from baseline to Day 85

  Total tau protein levels in cerebrospinal fluid. More frequent timepoints might be added as deemed necessary per the site Investigator's judgment.

  Baseline, Day 85

Secondary Outcomes (7)

• Number of adverse events and serious adverse events

  Cohort 1 & 2: Baseline up to 170 days (placebo-controlled part) and up to 589 days (OLE part), Cohort 3: Baseline up to 169 days (placebo-controlled part) and up to 507 days (OLE part)

• Concentration of NIO752 in cerebrospinal fluid (CSF)

  Cohorts 1 & 2: Pre-dose, Days 57, 85, 170 (placebo-controlled part) and Days 252, 420, and 588 (OLE part), Cohort 3: Pre-dose, day 1, 57, 85, 169 (placebo-controlled part) and Days 388 and 506 (OLE part)

• Cmax, Ctrough in plasma

  Cohorts 1, 2 & 3: Pre-dose, 0.5, 1, 2, 3 4, 5, 6, 24 hours post first dose. Cohort 1 & 2: Days 14, 57, 85 and 170 (pbo-controlled part) and 252, 253, 420, 421, and 588 (OLE) Cohort 3: Days 14, 57, 85 and 169 (pbo-controlled part) and 338 and 506 (OLE)

• Tmax in blood plasma

  Cohorts 1, 2 & 3: Pre-dose, 0.5, 1, 2, 3 4, 5, 6, 24 hours post first dose. Cohort 1 & 2: Days 14, 57, 85 and 170 (pbo-controlled part) and 252, 253, 420, 421, and 588 (OLE) Cohort 3: Days 14, 57, 85 and 169 (pbo-controlled part) and 338 and 506 (OLE)

• AUC-last in blood plasma

  Cohorts 1, 2 & 3: Pre-dose, 0.5, 1, 2, 3 4, 5, 6, 24 hours post first dose. Cohort 1 & 2: Days 14, 57, 85 and 170 (pbo-controlled part) and 252, 253, 420, 421, and 588 (OLE) Cohort 3: Days 14, 57, 85 and 169 (pbo-controlled part) and 338 and 506 (OLE)

Study Arms (8)

NIO752 - Dose A - Cohort 1

EXPERIMENTAL

A single intrathecal injection of Dose A

Drug: NIO752

Matching placebo - Cohort 1

PLACEBO COMPARATOR

A single intrathecal injection of artificial cerebrospinal fluid (CSF)

Drug: Matching placebo

NIO752 Dose B - Cohort 2

EXPERIMENTAL

A single intrathecal injection of Dose B

Drug: NIO752

Matching placebo - Cohort 2

PLACEBO COMPARATOR

A single intrathecal injection of artificial cerebrospinal fluid (CSF)

Drug: Matching placebo

NIO752 OLE - Cohorts 1 and 2

EXPERIMENTAL

Multiple intrathecal injections of Dose A

Drug: NIO752

NIO752 - Dose C - Cohort 3

EXPERIMENTAL

Two intrathecal injections of Dose C

Drug: NIO752

Matching Placebo - Cohort 3

PLACEBO COMPARATOR

Two intrathecal injections of artificial cerebrospinal fluid (CSF)

Drug: Matching placebo

NIO752 OLE - Cohort 3

EXPERIMENTAL

Single intrathecal injection of Dose C

Drug: NIO752

Interventions

NIO752 DRUG

A single intrathecal (cerebrospinal) injection of NIO752 of Dose A

NIO752 - Dose A - Cohort 1

Matching placebo DRUG

A single intrathecal injection of matching placebo

Matching placebo - Cohort 1; Matching placebo - Cohort 2

Eligibility Criteria

• Age: 30 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.
• 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.
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (10)

Novartis Investigative Site

Kuopio, 70210, Finland

COMPLETED

Novartis Investigative Site

Turku, 20520, Finland

COMPLETED

Novartis Investigative Site

Lille, 59037, France

RECRUITING

Novartis Investigative Site

Paris, 75013, France

RECRUITING

Novartis Investigative Site

Toulouse, 31059, France

RECRUITING

Novartis Investigative Site

Valencia, Valencia, 46017, Spain

RECRUITING

Novartis Investigative Site

Barcelona, 08036, Spain

RECRUITING

Novartis Investigative Site

Barcelona, 08041, Spain

RECRUITING

Novartis Investigative Site

Malmo, 221 85, Sweden

COMPLETED

Novartis Investigative Site

Stockholm, 141 86, Sweden

COMPLETED

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Memory Disorders

Condition Hierarchy (Ancestors)

Mental Disorders; Cognition Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Madhav Thambisetty, MD PhD

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1b

Study Record Dates

• First Submitted: July 11, 2022
• First Posted: July 21, 2022
• Study Start: February 23, 2023
• Primary Completion (Estimated): September 11, 2026
• Study Completion (Estimated): January 2, 2028
• Last Updated: August 28, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2); FI (2); FR (3); ES (3)