A 18-month Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Oral UCB0599 in Study Participants With Early-stage Parkinson's Disease (ORCHESTRA)

UCB

Status and phase: Completed; Phase 2

Conditions: Early-stage Parkinson's Disease

Treatments: Drug: UCB0599; Drug: Placebo

Study type: Interventional

Funder types: NETWORK; Industry

Identifiers

NCT04658186

PD0053

2020-003265-19 (EudraCT Number)

Details and patient eligibility

About

The purpose of the study is to assess the safety and tolerability of UCB0599 and to demonstrate the superiority of UCB0599 over placebo with regard to clinical symptoms of disease progression over 12 and 18 months in participants diagnosed with early-stage Parkinson's Disease.

Enrollment: 496 patients

Sex: All

Ages: 40 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Study participant must be 40 to 75 years of age inclusive, at the time of signing the informed consent
• Study participant has Parkinson's Disease (PD), with a diagnosis made by a neurologist according to the 2015 Movement Disorder Society criteria within 2 years of Baseline Visit (including diagnosis during Screening)
• The following diagnostic criteria must be met: bradykinesia AND at least ONE of the following: muscular rigidity, or resting tremor
• A Screening Dopamine Transporter Imaging with Single Photon Emission Computed Tomography (DaT-SPECT), or a historical DaT-SPECT within 3 months of the Screening Visit that has been qualified by the central reader, shows evidence of dopamine transporter deficit per study requirements and as determined by a central reader
• Study participant is in the ≤2.5 modified Hoehn and Yahr stage at Screening
• Study participant has never taken medications for the treatment of motor symptoms of PD and is not expected to require starting symptomatic treatment (ST) with a high likelihood in the next 6 months as far as clinical judgement allows
• Study participant has never taken part in disease-modifying treatment studies directed at neurodegenerative disease (NDD)
• Study participant does not take N-acetyl cysteine or other cysteine donors or glutathione precursors on a regular basis as a food supplement
• Study participant is willing, competent, and able to comply with all aspects of the protocol, including follow-up schedule and biospecimen collection
• Study participant has a body mass index (BMI) of 16 to 34kg/m² (inclusive)
• Contraception i) A male participant must agree to use contraception during the Treatment Period and for at least 90 days after the last dose ofstudy medication and refrain from donating sperm during this period ii) A female participant is eligible to participate if she is not pregnant, not breastfeeding, andat least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) OR A WOCBP who agrees to follow the contraceptive guidance during the Treatment Period and for at least 1 month after the last dose of study medication. The study participant must have a negative serum pregnancy test at Screening, which is to be confirmed negative by urine testing prior to the first dose of study medication at Baseline (Visit 3). If oral contraception is used, an additional barrier method will be required during the study as a study medication related-gastrointestinal upset or a drug interaction by CYP3A4 induction could interfere with efficacy

Exclusion criteria

• Study participant has a known hypersensitivity to any components (and/or its excipients) of the study medication or comparative drugs as stated in the protocol
• Study participant has a brain magnetic resonance imaging (MRI) scan performed during Screening indicative of a clinically significant abnormality or a historical MRI scan during the 6 months before Screening Visit 1 of sufficient quality to show such abnormalities. In case of doubt, the significance is determined on a case-by-case basis in close collaboration with the Medical Monitor and should not include abnormalities like age-appropriate brain atrophy, minor white matter signals, or mild vasculopathy
• Study participant has any contraindication for the brain MRI or Dopamine Transporter Imaging with Single Photon Emission Computed Tomography (DaT-SPECT) imaging
• Study participant has a Montreal Cognitive Assessment (MoCA) score less than 23, indicating mild cognitive impairment or other significant cognitive impairment or clinical dementia at Screening that, in the opinion of the Investigator, would interfere with study evaluation
• Study participant has abnormalities in lumbar spine previously known or determined by a Screening lumbar x-ray (if conducted) that could preclude lumbar puncture, in the opinion of the Investigator. The participant must be excluded from lumbar puncture but not from study participation
• Study participant has clinically significant electrocardiogram (ECG) abnormality at Screening, in the opinion of the Investigator
• Study participant has past history of use of medications for the treatment of motor symptoms of PD. Short (up to 4 weeks) past use of medications for the treatment of motor symptoms is permitted following a sufficient washout period. Medications included are: levodopa (maximum 400mg per day), dopamine agonists, monoamine oxidase B (MAO-B) inhibitors, anticholinergics, or amantadine. A sufficient washout period is at least 3 months prior to the Baseline Visit

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

496 participants in 3 patient groups, including a placebo group

UCB0599 High Dose Arm

Experimental group

Description:

Participants will be randomized to receive a predefined high dosage of UCB0599 during the Treatment Period.

Treatment:

Drug: UCB0599

Placebo Arm

Placebo Comparator group

Description:

Participants will be randomized to receive a predefined dosage of Placebo during the Treatment Period.

Treatment:

Drug: Placebo

UCB0599 Low Dose Arm

Experimental group

Description:

Participants will be randomized to receive a predefined low dosage of UCB0599 during the Treatment Period.

Treatment:

Drug: UCB0599