A Study to Evaluate the Efficacy of NIO752 in Participants With Progressive Supranuclear Palsy

Official title

A Phase III, Randomized, Placebo-controlled, Parallel Group, Double-blind Study to Evaluate the Efficacy and Safety of NIO752 in Participants With Progressive Supranuclear Palsy Followed by an Open Label Extension

Overview

This Phase III study is intended to evaluate the efficacy and safety of NIO752 in participants with Progressive Supranuclear Palsy (PSP). Eligible participants will be randomized to receive either NIO752 or placebo followed by an open-label extension.

Detailed description

This is a randomized, double-blind, placebo-controlled, parallel group, study to evaluate the efficacy of NIO752 in participants with Progressive Supranuclear Palsy followed by an open-label extension (OLE).

The participants with or without symptomatic therapy will be randomly allocated to either NIO752 or placebo treatment in a 2:1 randomization ratio.

Upon completion of the core double-blind treatment period, participants will be offered to continue with NIO752 treatment in the OLE.

Interventions

• Other NIO752
  Solution of antisense oligonucleotide.
• Drug Placebo
  Placebo solution

Primary outcome measures

• Change from baseline in the mPSPRS-10 score [Time frame: Baseline, Week 72]

Secondary outcome measures (11)

• Change from baseline in the PSPRS-28 items score [Time frame: Baseline, Week 72]
• Changes from baseline in activities of daily living on the Cortical Basal ganglia Functional Scale (CBFS) [Time frame: From baseline up to week 72]
• Change from baseline on the PSP-ShoQoL [Time frame: From baseline up to week 72]
• Change from baseline in Category (or Semantic) Fluency test over time [Time frame: From baseline up to week 72]
• Change from baseline in Letter (or Phonemic) Fluency test over time [Time frame: From baseline up to week 72]
• Change from baseline in Symbol Digit Modality Test (SDMT) over time [Time frame: From baseline up to week 72]
• Change from baseline in Letter-Number Sequencing task (LNS) over time [Time frame: From baseline up to week 72]
• Ratio to baseline of NfL (CSF) [Time frame: From baseline up to week 72]
• Ratio to baseline of CSF phospho-Tau-181 and CSF Total-Tau [Time frame: From baseline up to week 72]
• Changes from baseline in volumes of brain structures as measured by MRI [Time frame: From baseline up to week 72]
• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: From first treatment administration up to 72 weeks]

Eligibility criteria

Inclusion criteria

• Signed informed consent must be obtained prior to participation in the study.
• Male or female participants, age between 41-81 yrs inclusive.
• Diagnosis of mild-moderate, probable/possible PSP Richardson syndrome as per MDS-PSP 2017 criteria with symptoms onset < 5 years.
• PSPRS total score less than 40 at Baseline.
• Reliable study partner such as spouse, sibling, close friend, or caregiver 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 enough time (at least 5 hours per week) with the study participant.
• Participant is able to ambulate defined as the ability to take at least 10 steps independently or with minimal assistance (stabilization of one arm to minimize fall risk).
• Mini Mental State Examination (MMSE) score ≥ 20 at Screening.

Exclusion criteria

• Diagnosis of other significant neurological or psychiatric disorders including (but not limited to) Parkinsons' 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; seizure; brain tumor or other space-occupying lesion; history of clinically significant stroke (e.g., stroke with permanent 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 or other motor neuron diseases.
• Diagnosis of cerebellar ataxia, choreoathetosis, and early symptomatic autonomic dysfunction.
• History of or screening brain MRI scan indicative of significant abnormality, including, but not limited to, prior hemorrhage or infarct >1 cm3, >3 lacunar infarcts, cerebral contusion, aneurysm, vascular malformation >1 cm3, 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, including but not limited to:

• Known allergy to local anesthetic
• History of back surgery (with the exception of microdiscectomy or laminectomy over 1 level)
• Spinal deformities
• Current dermatological infection at the lumbar puncture spot and/or significant skin alterations at the planned puncture place
• Risk of increased or uncontrolled bleeding and/or risk of bleeding that if not managed optimally, could place a participant at an increased risk for 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).
• History of deep brain stimulator surgery other than sham surgery for participation in a deep brain stimulation clinical trial.

Other protocol-defined inclusion/exclusion criteria may apply

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Germany · 11 centers

• Novartis Investigative Site — Munich
• Novartis Investigative Site — Würzburg
• Novartis Investigative Site — Bonn
• Novartis Investigative Site — Düsseldorf
• Novartis Investigative Site — Dresden
• Novartis Investigative Site — Leipzig
• Novartis Investigative Site — Beelitz
• Novartis Investigative Site — Berlin
• … and 3 more centers

France · 8 centers

• Novartis Investigative Site — Caen
• Novartis Investigative Site — Créteil
• Novartis Investigative Site — Lille
• Novartis Investigative Site — Marseille
• Novartis Investigative Site — Nantes
• Novartis Investigative Site — Paris
• Novartis Investigative Site — Rennes
• Novartis Investigative Site — Toulouse

Spain · 8 centers

• Novartis Investigative Site — Pozuelo de Alarcón
• Novartis Investigative Site — Barcelona
• Novartis Investigative Site — Barcelona
• Novartis Investigative Site — Las Palmas GC
• Novartis Investigative Site — Madrid
• Novartis Investigative Site — Madrid
• Novartis Investigative Site — Madrid
• Novartis Investigative Site — Seville

United States · 5 centers

• Mayo Clinic Arizona — Scottsdale
• Univ of California San Francisco — San Francisco
• CenExcel Rocky Mtn Clin Research — Englewood
• Mayo Jacksonville — Jacksonville
• Mayo Clinic — Rochester

Australia · 2 centers

• Novartis Investigative Site — Westmead
• Novartis Investigative Site — Melbourne

China · 2 centers

• Novartis Investigative Site — Shanghai
• Novartis Investigative Site — Suzhou

Italy · 2 centers

• Novartis Investigative Site — Milan
• Novartis Investigative Site — Roma

Netherlands · 2 centers

• Novartis Investigative Site — Rotterdam
• Novartis Investigative Site — Nijmegen

Japan · 1 center

• Novartis Investigative Site — Kodaira

South Korea · 1 center

• Novartis Investigative Site — Seoul

Identifiers

NCT: NCT07498426 · CNIO752A12301

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗