A Study to Evaluate the Safety, Tolerability and Pharmacodynamics of NIO752 in Primary Tauopathies

NCT07868328 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CNIO752A12201
• Study Type: interventional
• Target: 48
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a phase II study intended to evaluate the safety, tolerability and pharmacodynamics of NIO752 in participants with primary tauopathies. Eligible participants will be randomized to receive either NIO752 or placebo during the double-blind treatment period followed by an Open-label Extension (OLE).

Conditions

Progressive Supranuclear Palsy; Corticobasal Degeneration; Frontotemporal Lobar Degeneration; Tauopathies

Keywords

PSP non-Richardson syndrome (PSP non-RS); Corticobasal syndrome, amyloid-negative (CBS non-AD); MAPT mutation carriers (MAPT-FTLD); NIO752; Antisense Oligonucleotide (ASO); Microtubule Associated Protein Tau (MAPT); Double-blind; Intrathecal

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) in double blind period

  Number of participants with TEAEs including SAEs, AESIs, and AEs leading to treatment interruption/discontinuation or dose reduction.

  From first treatment administration up to week 48

Secondary Outcomes (9)

• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) in open-label extension

  From first treatment administration in OLE period up to week 96

• Change from baseline in clinical laboratory evaluations

  From baseline up to week 96

• Change from baseline in vital signs

  From baseline up to week 96

• Change from baseline in ECG parameters

  From baseline up to week 96

• Suicidality assessment using the C-SSRS

  From baseline up to week 96

Study Arms (6)

NIO752 - Cohort 1 (PSP non-RS)

EXPERIMENTAL

NIO752 solution

Drug: NIO752

Placebo - Cohort 1 (PSP non-RS)

PLACEBO COMPARATOR

Placebo solution

Drug: Placebo

NIO752 - Cohort 2 (CBS non-AD)

EXPERIMENTAL

NIO752 solution

Drug: NIO752

Placebo - Cohort 2 (CBS non-AD)

PLACEBO COMPARATOR

Placebo solution

Drug: Placebo

NIO752 - Cohort 3 (MAPT-FTLD)

EXPERIMENTAL

NIO752 solution

Drug: NIO752

Placebo - Cohort 3 (MAPT-FTLD)

PLACEBO COMPARATOR

Placebo solution

Drug: Placebo

Interventions

NIO752 DRUG

Antisense Oligonucleotide Solution

NIO752 - Cohort 1 (PSP non-RS); NIO752 - Cohort 2 (CBS non-AD); NIO752 - Cohort 3 (MAPT-FTLD)

Placebo DRUG

Placebo solution

Placebo - Cohort 1 (PSP non-RS); Placebo - Cohort 2 (CBS non-AD); Placebo - Cohort 3 (MAPT-FTLD)

Eligibility Criteria

• Age: 41 Years - 81 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Common across all cohorts:
• Signed informed consent must be obtained prior to participation in the study.
• Participants between the ages of ≥41 and ≤81 years.
• Able to walk at least 10 steps with minimal assistance (stabilization of one arm or use of cane/walker).
• Documented symptom (clinical manifestation) onset in the past ≤5 years prior to screening, defined as the first emergence of disease related motor, cognitive, or behavioral symptoms that led to measurable impairment in instrumental or basic activities of daily living (iADLs/ADLs), based on clinical history or reliable informant report.
• Reliable study partner(s) such as spouse, sibling, close friend or partner, family member or caregiver who are able and willing to provide accurate information (including clinical symptoms and medical history) about the participant and to participate in study visits and informant-based assessments for the duration of the study. A reliable study partner is expected to spend sufficient time (near-daily contact) with the study participant
• If participant is receiving symptomatic medication, the dose must have been stable for at least 8 weeks prior to randomization.
• Cohort specific criteria:

You may not qualify if:

• Diagnosis of other significant neurological or psychiatric disorders including (but not limited to) Parkinson's' Disease (which has not subsequently been revised to a diagnosis of PSP); Alzheimer's disease (AD), dementia with Lewy bodies; prion disease; any psychotic disorders; severe Major Depressive Disorder (MDD); history of epilepsy or seizure disorder (excluding febrile seizures in childhood); brain tumor or other space occupying lesion (e.g., brain tumor, subdural hematoma, abscess, or any intracranial mass causing compression or structural distortion) ; history of clinically significant stroke (e.g., stroke with neurological deficit); history of head injury with loss of consciousness for at least 15 minutes within the past 20 years.
• Diagnosis of amyotrophic lateral sclerosis and/or motor neuron disease.
• Diagnosis of cerebellar ataxia, choreoathetosis, and early symptomatic autonomic dysfunction.
• History of or screening brain Magnetic Resonance Imaging (MRI) scan indicative of significant abnormality, including, but not limited to, prior intracerebral hemorrhage or infarct \>1 cm diameter, \>3 lacunar infarcts, cerebral contusion, aneurysm, vascular malformation \>1 cm diameter, subdural hematoma, hydrocephalus, and space-occupying lesion (e.g., abscess or brain tumor).
• Contraindications to undergo MRI procedure, including metal (ferromagnetic) implants and/or a cardiac pacemaker that is not compatible with MRI.
• Medical conditions that would as per Investigator's judgement prevent the participant from undergoing lumbar puncture (LP), including but not limited to:
• History of/ known allergy to local anesthetic
• History of back surgery (except for microdiscectomy or laminectomy at level one)
• Spinal deformities that would interfere with i.t. administration or CSF flow
• Current dermatological infection at the LP site and/or significant skin alterations at the planned LP site:
• Presence of increased or uncontrolled bleeding and/or risk of bleeding that if not managed optimally could increase a participant's likelihood of procedural bleeding. These could include but are not limited to anatomical factors at or near the LP site (e.g., vascular abnormalities, neoplasms) and underlying disorders of coagulation, platelet function or platelet count (e.g., abnormal coagulation parameters, hemophilia, Von Willebrand's disease, liver disease).
• Participants on anticoagulants (e.g., warfarin) or antiplatelets therapies \[except for low dose aspirin (100 mg/day or lower) and low-dose ibuprofen (600 mg/day or lower) which are allowable\], are not eligible to participate, unless temporal suspension of the anticoagulant or antiplatelet therapies for the purpose of the LP is considered safe for the patient, feasible, and guided by a hematologist.
• History of deep brain stimulator surgery other than sham surgery for participation in a deep brain stimulation clinical trial.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

MeSH Terms

Conditions

Supranuclear Palsy, Progressive; Corticobasal Degeneration; Frontotemporal Lobar Degeneration; Tauopathies; Pick Disease of the Brain

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Neurodegenerative Diseases; Paralysis; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Dementia; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders; Mental Disorders; Frontotemporal Dementia

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind for the core treatment period; open-label NIO752 for all participants in the extension; raters blinded to safety data.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel arm basket trial with 3 cohorts for the double blind period

Study Record Dates

• First Submitted: October 5, 2026
• First Posted: October 9, 2026
• Study Start (Estimated): October 23, 2026
• Primary Completion (Estimated): March 26, 2029
• Study Completion (Estimated): May 20, 2030
• Last Updated: October 9, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will share