A Trial Investigating Lu AF28996 in Adults With Parkinson's Disease Who Have Motor Fluctuations (DARE2)

Interventional, Randomized, Double-blind, Parallel-group, Placebo-controlled, Flexible-dose Trial of Lu AF28996 in Adults With Parkinson's Disease Experiencing Motor Fluctuations

This trial will evaluate the effects of Lu AF28996 in adults with Parkinson's disease (PD) experiencing motor fluctuations despite optimized non-invasive symptomatic treatment. These are individuals with PD who take medications to control movement symptoms, such as slowness, stiffness, and tremor, but still experience periods of time when their medication does not adequately control their motor symptoms. Some may also experience dyskinesia (other type of involuntary movements) as a side effect of their PD medications. The main goal of the trial is to learn whether adding Lu AF28996 to participants' optimized PD medications will help extending the time they spend with their movement symptoms being well-controlled and without bothersome dyskinesia.

Study Overview

• Status: Not yet recruiting
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Lu AF28996; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Email contact via H. Lundbeck A/S; Phone Number: +45 36301311; Email: HQ_Medinfo@Lundbeck.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• The participant was diagnosed with PD ≥3 years ago, with the diagnosis being established after the age of 30 years and consistent with the Movement Disorders Society (MDS) Clinical Diagnostic Criteria for "clinically established" or "clinically probable" PD.
• The participant has a modified Hoehn and Yahr scale (mH&Y) stage ≤3 in the ON state and ≥2 and ≤4 in the OFF state.
• The participant reports well recognizable, consistent motor fluctuations causing significant disability per investigator's judgement over a period of ≥3 months prior to screening.
• The participants report motor fluctuations each day as measured by OFF-time during awake hours.

Key Exclusion Criteria:

• The participant has previously been dosed with Lu AF28996.
• The participant has participated in a clinical trial <30 days prior to screening.
• The participant is pregnant, breastfeeding, intends to become pregnant, or is of child-bearing potential and not willing to use adequate contraceptive methods.
• The participant has taken any investigational medicinal product (IMP) <3 months or <5 half-lives, whichever is longer, prior to screening.
• The participant has a Montréal Cognitive Assessment (MoCA) score ≤24 (adjusted for education).
• The participant has an atypical, secondary, or drug-induced Parkinsonism (for example, metoclopramide, flunarizine), metabolic identified neurogenetic disorders (for example, Wilson's disease), encephalitis, or Parkinson Plus syndromes or other forms of atypical Parkinsonian syndromes (for example, progressive supranuclear palsy and multiple system atrophy).
• The participant has severe, pervasive, disabling dyskinesia which, in the setting of the present trial, may interfere with his/her safe participation in the trial (for example, threat to falling, aspiration, etc.) as judged by the investigator.
• The participant has unpredictable motor fluctuations as evidenced by an MDS-UPDRS Part IV Item 4.5 score ≥3 at screening and/or experiences wide, unpredictable fluctuations of PD symptoms per investigator's clinical judgement.

Note: Other protocol defined inclusion and exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lu AF28996; Participants will receive Lu AF28996 as add-on to concomitant PD medications for up to Week 23.	Drug: Lu AF28996; Lu AF28996 will be administered orally per schedule specified in the arm description.
Placebo Comparator: Placebo; Participants will receive Lu AF28996 matching placebo as add-on to concomitant PD medications for up to Week 23.	Drug: Placebo; Placebo matching to Lu AF28996 will be administered orally per schedule specified in the arm description.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline to Week 19 in Daily Good ON Time Based on the Participant's Hauser Diary Entries	Baseline, Week 19

Secondary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline to Week 19 in Daily OFF Time Based on Participant's Hauser Diary Entries	Baseline, Week 19
Change From Baseline to Week 19 in Daily ON Time With Troublesome Dyskinesia Based on Participant's Hauser Diary Entries in Participants Reporting ≥1 Hour of Daily ON Time With Troublesome Dyskinesia at Baseline	Baseline, Week 19
Change From Baseline to Week 19 in Participant's Unified Dyskinesia Rating Scale (UDysRS) Total Score in Participants Reporting ≥1 Hour of Daily ON Time With Troublesome Dyskinesia at Baseline	Baseline, Week 19
Participant's Achievement at Week 19 of a Reduction in Daily OFF Time, Defined as >1.5 Hour/Day Reduction	Week 19
Participant's Achievement at Week 19 of an Increase in Daily Good ON Time >1.5 Hour/Day	Week 19
Participant's Achievement at Week 19 of a Reduction in Both Daily ON Time With Troublesome Dyskinesia AND in OFF time in Participants Reporting ≥1 Hour of Daily ON Time With Troublesome Dyskinesia at Baseline	Week 19
Change From Baseline to Week 19 in Clinical Global Impression - Severity of Illness (CGI-S) Score	Baseline, Week 19
Change From Baseline to Week 19 in Participant's Movement Disorder Society-Unified Parkinson's Disease-Rating Scale (MDS-UPDRS) Part III Score	Baseline, Week 19
Change From Baseline to Week 19 in Participant's Movement Disorders Society Non-Motor Rating Scale (MDS-NMS) Domain Scores and Total Score	Baseline, Week 19
Change From Baseline to Week 19 in Participant's Parkinson's Disease Sleep Scale Version 2 (PDSS-2) Total Score	Baseline, Week 19
Change From Baseline to Week 19 in Participant's MDS-UPDRS Part IV (B) (Questions 4.1, 4.2, 4.3, 4.4 Item Scores), and Part IV Score	Baseline, Week 19
Change From Baseline to Week 19 in Participant's MDS-UPDRS Total Score	Baseline, Week 19
Change From Baseline to Week 19 in Participant's MDS-UPDRS Part I Score	Baseline, Week 19
Change From Baseline to Week 19 in Participant's MDS-UPDRS Part II Score	Baseline, Week 19
Change From Baseline to Week 19 in Participant's Parkinson's Disease Questionnaire-39 (PDQ-39) Score	Baseline, Week 19
Change From Baseline to Week 19 in Participant's EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L) Visual Analogue Scale Score	Baseline, Week 19
Change From Baseline to Week 19 in Daily Oral Levodopa (mg)	Baseline, Week 19
Change From Baseline to Week 19 in Levodopa-equivalent Dose (LED)	Baseline, Week 19
Change From Baseline to Week 19 in Total Levodopa-equivalent Daily Dose (LEDD)	Baseline, Week 19
Patient Global Impression of Change (PGI-C) Score at Week 19	Week 19
Plasma Concentrations of Lu AF28996 and Metabolites	Weeks 7 and 15
Change From Baseline to Week 19 in Daily ON Time With Troublesome Dyskinesia Based on Participant's Hauser Daily Entries	Baseline, Week 19
Change From Baseline to Week 19 in Daily ON Time Without Troublesome Dyskinesia Based on Participant's Hauser Daily Entries	Baseline, Week 19
Change From Baseline to Week 19 in Daily ON Time With Non-troublesome Dyskinesia Based on Participant's Hauser Daily Entries	Baseline, Week 19
Change From Baseline to Week 19 in Participant's UDysRS Total Score and Combined Partial Scores of Part 1 + Part 2, Part 3 + Part 4, and Part 1 + Part 3 + Part 4, in Participants With UDysRS Total Score ≥20 at Baseline	Baseline, Week 19
Number of Participants With Achievement of a Reduction in Daily ON Time With Troublesome Dyskinesia at Week 19	Week 19
Number of Participants With Achievement of No Worsening in Daily ON Time With Troublesome Dyskinesia at Week 19	Week 19

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S
• Investigators: Study Director: Email contact via H. Lundbeck A/S, H. Lundbeck A/S

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: March 31, 2026
• First Submitted That Met QC Criteria: March 31, 2026
• First Posted (Actual): April 7, 2026

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease
• Other Study ID Numbers: 20309A

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No