Study of Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of NIO752 in Early Alzheimer's Disease Participants
- Conditions
- Alzheimer’s Disease
- Interventions
- Drug: Matching placebo
- Registration Number
- 2024-514004-14-00
- Lead Sponsor
- Novartis Pharma AG
- 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 36 patients with early AD will be enrolled in one of three cohorts.
Cohorts 1 \& 2 will receive a single intrathecal (IT) dose of NIO752 or placebo in the placebo-controlled part of the study, and multiple administrations of NIO752 in the open-label extension (OLE) part of the study.
Cohort 3 will receive two single IT doses of NIO752 or placebo in the placebo-controlled part of the study, and a single administration of NIO752 in the OLE part of the study.
Each cohort will enroll 12 participants, and they will be randomized into receiving NIO752 or placebo in 2:1 ratio. Participants in cohorts 1\& 2 will remain in this study for approximately \~19 months, including \~18 in-clinic follow up visits during that period of time. In cohort 3, participants will remain in this study for a follow up period of approximately \~18 months including \~10 in-clinic follow up visits.
Cohorts will be enrolled sequentially.
Participants who complete the placebo-controlled part of the study will be eligible to continue in an OLE part of the study regardless of randomization assignment in the placebo-controlled part. All OLE participants will receive either two (cohorts 1 \& 2) or one (cohort 3) dose of NIO752.
Study assessments will include physical and neurological examinations, ECGs, vital signs, standard clinical laboratory evaluations (hematology, blood chemistry, and urinalysis), routine laboratory evaluation of CSF collected through lumbar puncture, adverse event, and serious adverse event monitoring. Cohort 3 participation will also require 3 MRI scans and 3 PET scans throughout the 18 months of the study.
Recruitment & Eligibility
- Status
- Ongoing, recruitment ended
- Sex
- All
- Target Recruitment
- 37
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description NIO752 - Dose A - Cohort 1 NIO752 A single intrathecal injection of Dose A Matching placebo - Cohort 1 Matching placebo A single intrathecal injection of artificial cerebrospinal fluid (CSF) NIO752 Dose B - Cohort 2 NIO752 A single intrathecal injection of Dose B Matching placebo - Cohort 2 Matching placebo A single intrathecal injection of artificial cerebrospinal fluid (CSF) NIO752 OLE - Cohorts 1 and 2 NIO752 Multiple intrathecal injections of Dose A NIO752 - Dose C - Cohort 3 NIO752 Two intrathecal injections of Dose C Matching Placebo - Cohort 3 Matching placebo Two intrathecal injections of artificial cerebrospinal fluid (CSF) NIO752 OLE - Cohort 3 NIO752 Single intrathecal injection of Dose C
- Primary Outcome Measures
Name Time Method Change in cerebrospinal total tau from baseline to Day 85 Baseline, Day 85 Total tau protein levels in cerebrospinal fluid. More frequent timepoints might be added as deemed necessary per the site Investigator's judgment.
- Secondary Outcome Measures
Name Time Method 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) Adverse events are assessed at each clinic visit. Laboratory values and other safety assessment values considered clinically significant by the investigator and meet the definition of adverse event will be reported.
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) Concentration of NIO752 in CSF
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) Maximum and trough level concentrations of NIO752 in plasma
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) Time of Cmax in plasma post-IT injection
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) Area under curve (AUC) from time zero to the last measurable concentration sampling time (t-last) (mass x time x volume-1)
AUC-inf 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) The AUC from time zero to infinity (mass x time x volume-1)
Change in CSF total Tau 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) Evaluating the ability of NIO752 to lower CSF total tau in participants with early AD when administered as multiple doses
Trial Locations
- Locations (10)
Assistance Publique Hopitaux De Paris
🇫🇷Paris Cedex 13, France
Centre Hospitalier Universitaire De Lille
🇫🇷Lille Cedex, France
Centre Hospitalier Universitaire De Toulouse
🇫🇷Toulouse, France
Clinical Research Services Turku CRST Oy
🇫🇮Turku, Finland
University Of Eastern Finland
🇫🇮Kuopio, Finland
Region Skane Skanes Universitetssjukhus
🇸🇪Malmo, Sweden
Karolinska University Hospital
🇸🇪Huddinge, Sweden
Hospital De La Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Dr Peset Aleixandre
🇪🇸Valencia, Spain
Hospital Clinic De Barcelona
🇪🇸Barcelona, Spain
Assistance Publique Hopitaux De Paris🇫🇷Paris Cedex 13, FranceNicolas VILLAINSite contact+33142167502nicolas.villain@aphp.fr