Clinical trial NCT06809400: A Study of LY4006896 in Healthy Participants and Participants With Parkinson's Disease
Official title: A Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY4006896 in Healthy Participants and Participants With Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Parkinson Disease
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2025-02-05
Enrollment: 127
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to generate evidence of the safety, tolerability, and pharmacokinetics/pharmacodynamics of IV LY4006896 compared with placebo in healthy participants and participants with Parkinson's disease.

Detailed description: The screening period will be up to 120 days for participants with Parkinson's disease who receive 4 doses, and up to 35 days for healthy participants who receive 1 dose. The treatment and follow-up duration will be up to 61 weeks for participants with Parkinson's disease, and 48 weeks for healthy participants. The total study duration will be up to 78 weeks for participants with Parkinson's disease, and 53 weeks for healthy participants.

Eligibility criteria: Inclusion Criteria:

Part A Single Ascending Dose (SAD) and B Multiple Ascending Dose (MAD)

* Have a body mass index within the range of 18 to 34 kilogram/square meter (kg/m²) (inclusive).
* For Japanese participants: To qualify as a participant of first-generation Japanese origin, the participant, the participant's biological parents, and all of the participant's biological grandparents must be of exclusive Japanese descent and born in Japan.
* Have venous access sufficient to allow for blood sampling or administration of study intervention for IV administration, or both.

Part A (SAD) Only

* Are overtly healthy
* For Chinese participants: To qualify as Chinese for this study, all 4 of the participant's biological grandparents must be exclusive Chinese descent and born in China.

Part B (MAD) Only

* Diagnosis of Parkinson's disease per United Kingdom (UK) Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria.
* If presently untreated for Parkinson's disease, clinical status is not expected to require changes in symptomatic treatment within 52 weeks from baseline.
* If presently being treated for Parkinson's disease, receiving a stable dose of symptomatic dopaminergic therapy, including monoamine oxidase-B inhibitor, levodopa/carbidopa or dopamine agonist for at least 90 days prior to baseline and not expected to change within 52 weeks.
* Have a Montreal Cognitive Assessment (MoCA) score of greater than or equal to (≥) 26.

Exclusion Criteria:

Part A (SAD) and B (MAD)

* Have significant neurological disease affecting the central nervous system (CNS) (other than Parkinson's disease in Part B cohorts) that may affect the participant's ability to complete the study.
* Have a history or presence of serious or unstable illnesses or conditions that, in the investigator's opinion, could interfere with the analyses in this study, or increase risk for study intervention administration, or result in a participant's life expectancy of less than 24 months.
* Have known allergies to LY4006896, related compounds, or any components of the formulation, or history of allergic reactions to any transferrin receptor antibodies.
* Have significant allergies to humanize monoclonal antibodies.
* Have clinically significant multiple or severe drug allergies (including, but not limited to, erythema multiforme major, linear immunoglobulin A dermatosis, toxic epidermal necrolysis, or exfoliative dermatitis); or intolerance to topical corticosteroids, or severe posttreatment hypersensitivity reactions.
* Have history or presence of uncontrolled asthma, significant autoimmune disease, hereditary angioedema, or known history of common variable immune deficiency.
* Evidence of clinically significant anemia.

Part A (SAD) Only

* Have an abnormal blood pressure or pulse rate, or both, as determined by the investigator, or a preexisting history of hypertension.

Part B (MAD) Only

* Have an abnormal blood pressure or pulse rate, or both, as determined by the investigator, or have uncontrolled hypertension, defined as a systolic blood pressure \>150 mm Hg or a diastolic blood pressure \>95 mm Hg at Screening or Treatment Visits.

Primary outcomes:
measure: Number of Participants with One or More Serious Adverse Event(s) (SAEs) Part A
timeFrame: Baseline to Week 48
measure: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Part A
timeFrame: Baseline to Week 48
measure: Number of Participants with One or More Serious Adverse Event(s) (SAEs) Part B
timeFrame: Baseline to Week 61
measure: Number of Participants with TEAEs Part B
timeFrame: Baseline to Week 61
Secondary outcomes:
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY4006896 Part A
timeFrame: Baseline to Week 48
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY4006896 Part B
timeFrame: Baseline to Week 61
measure: PK: Area Under the Concentration versus Time Curve (AUC) of LY4006896 Antibody-Small Interfering RNA (siRNA) Conjugate (ARC)-associated antisense Part A
timeFrame: Baseline to Week 48
measure: PK: AUC of LY4006896 ARC-Associated Antisense Part B
timeFrame: Baseline to Week 61
Other outcomes:
Locations:
city: Los Alamitos
country: United States
facility: Collaborative Neuroscience Network - CNS
state: California
city: Los Alamitos
country: United States
facility: Collaborative Neuroscience Network - CNS
state: California
city: Maitland
country: United States
facility: K2 Medical Research, LLC
state: Florida
city: Naples
country: United States
facility: Aqualane Clinical Research
state: Florida
city: Orlando
country: United States
facility: Charter Research
state: Florida
city: The Villages
country: United States
facility: K2 Summit Research
state: Florida
city: The Villages
country: United States
facility: Charter Research
state: Florida
city: Decatur
country: United States
facility: Accel Research Sites - NeuroStudies Clinical Research Unit
state: Georgia
city: Farmington Hills
country: United States
facility: QUEST Research Institute
state: Michigan
city: Austin
country: United States
facility: PPD Development, LP
state: Texas
city: Kirkland
country: United States
facility: Evergreen Health Research
state: Washington
city: Yufu
country: Japan
facility: Oita University Hospital
state: Oita
city: Hachioji
country: Japan
facility: P-One Clinic
state: Tokyo
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: