Safety, Tolerability, and Pharmacokinetics of Exidavnemab in Patients with Parkinson's Disease

Phase 2

Recruiting

• Conditions: Parkinson Disease
• Interventions: Drug: exidavnemab; Drug: Placebo Comparator

• Registration Number: NCT06671938
• Lead Sponsor: BioArctic AB

Brief Summary

The primary objective of this study is to assess the safety and tolerability of exidavnemab after multiple dosing versus placebo.

Detailed Description

This Phase 2a, randomized, double-blind, placebo-controlled, multicenter, multinational, multiple ascending dose (MAD) trial is designed to investigate the safety, tolerability, and pharmacokinetics (PK) of exidavnemab in participants with mild to moderate Parkinson's Disease (PD) on stable symptomatic PD medication. The trial will evaluate two dose cohorts versus placebo. Participants in each cohort will be randomly allocated in a 2:1 ratio to receive either exidavnemab or placebo. There will be 12 evaluable participants in each cohort, and approximately 24 participants randomized in total.

Study Timeline

• Study First Submitted: 2024-09-19
• Study Start: 2024-10-24
• Study First Submitted QC: 2024-11-01
• Study First Posted: 2024-11-04
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-09
• Last Update Posted: 2024-12-12
• Primary Completion: 2026-03-16
• Study Completion: 2026-03-16

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Male and female participants 40 to 85 years of age.
2. Body weight more than or equal to 50 kg and less than or equal to 120 kg.
3. Have Idiopathic PD (i.e., not induced by drugs or other diseases) as defined by bradykinesia combined with at least 1 of resting tremor and rigidity, as per the Movement Disorder Society Criteria for PD (Postuma, et al. 2015).
4. Classified as Stage 1 to 2.5 on the modified Hoehn and Yahr scale for the staging of PD severity.
5. Participants must have cognition inconsistent with dementia as confirmed by a score of more than or equal to 22 on the MoCA.
6. Stable and optimized symptomatic PD medication, defined as the same list of medications for at least 3 months prior to the Screening Visit with no change in the dose for at least 1 month prior to the Baseline Visit, and no planned changes in dose-regimen during trial participation.
7. Prior (any time; i.e., no time limit) or current DaT-SPECT or DaT-PET consistent with dopamine transporter deficit, as per the Movement Disorder Society Criteria for PD(Postuma, et al. 2015). For participants who have not undergone DaT-SPECT or DaT-PET prior to Screening, or who have previously undergone DaT-SPECT or DaT-PET scan(s) but without results consistent with dopamine transporter deficit, DaT-SPECT or DaT-PET should be performed and read locally as part of the Screening procedures.
8. Positive smell test showing hyposmia, as defined by UPSIT scores of around or below the 15% percentile for their relevant sex and age group. Cut-off scores are provided below for reference (Table 5.1; based on Brumm, et al. 2023) Ability to use a tablet device to measure cognitive function, as per Investigator judgment.

Exclusion Criteria

1. Known hypersensitivity to trial medication, the infusion solution, or excipients.
2. More than 5 years of symptomatic treatment for PD.
3. History of neurosurgical intervention for PD including implantation of brain stimulation.
4. Diagnosis of PD dementia or another dementia.
5. Any psychiatric diagnosis or symptoms (e.g., hallucinations, major depression, or delusions) that could interfere with trial procedures.
6. Freezing episodes occurring on a weekly basis or more frequently.
7. Motor fluctuations occurring on a weekly basis or more frequently.
8. Levodopa-induced troublesome dyskinesia of a severity that would significantly interfere with the participant's ability to participate or perform trial procedures as determined by the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Subscale IV.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
exidavnemab	exidavnemab	exidavnemab (cohort 1 - dose 1; cohort 2 - dose 2)
Placebo	Placebo Comparator	-

Primary Outcome Measures

Name	Time	Method
Number of participants with adverse events (AEs), serious adverse events (SAEs) and withdrawals due to AEs.	From first dose to Day 176	Number of participants with adverse events (AEs), serious adverse events (SAEs) and withdrawals due to AEs.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic (Plasma): Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (Clast)	Day 1 and Day 85	PK parameters (AUClast) following single dose, as calculated by the linear trapezoidal method
Establishment of an appropriate dose range for proof-of-concept trial	From first dose to Day 176	The recommended maximal dose will be defined by the safety and tolerability profile and PK data
Assessment of systemic immunogenicity effects of exidavnemab	From first dose to Day 176	Determination of ADAs in serum by using a tier-based approach followed by determination of NAbs if relevant.

Trial Locations

Locations (6)

Hospital Universitari General de Catalunya; 🇪🇸 Sant Cugat del Valles, Barcelona, Spain

Centrum Medyczyne Neuromed Sp. z o.o.; 🇵🇱 Bydgoszcz, Poland

Specjalistyczne Gabinety Sp. z o.o.; 🇵🇱 Krakow, Poland

Krakowska Akademia Neurologii Sp. Z o.o; 🇵🇱 Krakow, Poland

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

Policlínica Gipuzkoa; 🇪🇸 San Sebastián, Spain