Study to Assess PDM608 in Healthy Adult Subjects

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, tolerability and pharmacokinetics of PDM608 in healthy adult subjects.

Detailed Description
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This is a 2-part, single-center, first-in-human study of single ascending doses (SAD; Part 1) and multiple ascending doses (MAD; Part 2) of PDM608 in healthy adult subjects. Part 1 is a double-blind, randomized, placebo-controlled assessment of subcutaneous (SC) SAD administrations of PDM608 across 5 cohorts of subjects. All SAD cohorts will follow a sentinel design. Following completion of each cohort, safety and tolerability data through 96 hours post-dose will be reviewed to determine whether to progress to the next dose level and the dose level for the next cohort. Part 2 is a double-blind, randomized, placebo-controlled assessment of SC MAD administrations (once weekly for 4 weeks) of PDM608 across up to 4 cohorts of subjects. Following completion of each cohort the safety and tolerability data 96 hours post last dose will be reviewed to determine whether to progress to the next dose level and the dose level to be administered.

Official Title
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A Two-Part Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of PDM608 in Healthy Adult Subjects

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: PDM608
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men, or women of non-childbearing potential Must agree to use an adequate method of contraception Body mass index (BMI) of 18.0 to 33.0 kg/m2 as measured at screening Exclusion Criteria: Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients Significant allergy requiring treatment History of clinically significant autoimmune, cardiovascular, renal, hepatic, chronic respiratory or GI disease (except cholecystectomy), neurological or psychiatric disorder, illness/infection/hospitalization or surgical procedure within 30 days prior to first dose of study drug or any uncontrolled medical illness as judged by the investigator Have poor venous access that limits phlebotomy Evidence of current SARS-CoV-2 infection or exposure to confirmed infection within 10 days prior to the first dose of study drug Clinically significant abnormal clinical chemistry, hematology or urinalysis Hepatitis B, Hepatitis C, HIV, TB Renal impairment Pregnant or lactating women or men with pregnant or lactating partners Received any IMP in a clinical research study within 5 half-lives or within 30 days prior to first dose (whichever is longer) Taking any prescribed or over-the-counter drug or herbal remedies (other than up to 4 g per day acetaminophen and HRT) in the 14 days or 5 half-lives (whichever is longer) before IMP administration COVID-19 vaccine within 14 days prior to first dose or have a COVID-19 vaccine scheduled between their first dose of IMP and last dose of IMP. Drug or alcohol abuse in the past 2 years Regular alcohol consumption in men >21 units per week and women >14 units per week (1 unit = 12 oz 1 bottle/can of beer, 1 oz 40% spirit or 5 oz glass of wine) Positive alcohol urine test at screening or first admission Current and within the last six months-smokers, e-cigarettes and nicotine replacement users Donation of blood within 2 months or donation of plasma within 7 days prior to first dose of study medication Subjects who are, or are immediate family members of, a study site or Sponsor employee

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Part 1 Cohorts 1-5 will assess single ascending doses (SAD) of subcutaneous administration PDM608. Part 2 will assess multiple ascending doses (MAD) administrations given once weekly for 4 weeks in up to 4 cohorts of participants. The parts of the study are not required to be conducted entirely sequentially, provided that this is justified by PK and safety data obtained from completed cohorts. The first MAD cohort will not start until data are available from SAD Cohort 3 and dosing for each MAD cohort will not exceed the a dose level previously deemed safe in a SAD cohort.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 SAD SC PDM608<br>Single ascending dose, subcutaneous administration of PDM608 | Drug: PDM608<br>* PDM608 subcutaneous at single or multiple dose(s) assigned by cohort<br>|
| Placebo Comparator: Part 1 SAD SC Placebo<br>Single ascending dose, subcutaneous administration of matching placebo | Drug: Placebo<br>* Placebo subcutaneous at single or multiple dose(s) to match PDM608 administration.<br>|
| Experimental: Part 2 MAD SC PDM608<br>Multiple ascending dose, subcutaneous administration of PDM608 once weekly for 4 weeks. | Drug: PDM608<br>* PDM608 subcutaneous at single or multiple dose(s) assigned by cohort<br>|
| Placebo Comparator: Part 2 MAD SC Placebo<br>Multiple ascending dose, subcutaneous administration of placebo once weekly for 4 weeks. | Drug: Placebo<br>* Placebo subcutaneous at single or multiple dose(s) to match PDM608 administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | Adverse events will be analyzed for severity and potential relationship to PDM608 to determine safety and tolerability of PDM608 | Part 1: Day 1 through Day 5; Part 2: Day 1 through Day 26 | 
| Number of participants with clinically significant abnormal laboratory test results | Results outside of laboratory defined normal ranges will be analyzed for clinical significance and used to determine safety and tolerability of PDM608 | Part 1: Day 1 through Day 5; Part 2: Day 1 through Day 26 | 
| Number of participants with abnormal electrocardiogram readings: QTcF | Abnormal QTcF interval | Part 1: Day 1 through Day 5; Part 2: Day 1 through Day 26 | 
| Number of participants with abnormal electrocardiogram readings: VR | Abnormal ventricular rate | Part 1: Day 1 through Day 5; Part 2: Day 1 through Day 26 | 
| Number of participants with abnormal electrocardiogram readings: PR interval | Abnormal PR interval | Part 1: Day 1 through Day 5; Part 2: Day 1 through Day 26 | 
| Number of participants with abnormal electrocardiogram readings: QRS duration | Abnormal QRS duration | Part 1: Day 1 through Day 5; Part 2: Day 1 through Day 26 | 
| Number of participants with abnormal electrocardiogram readings: QRS axis | Abnormal QRS axis | Part 1: Day 1 through Day 5; Part 2: Day 1 through Day 26 | 
| Number of participants with abnormal vital signs: BP | Abnormal systolic and/or diastolic pressure (mmHg) | Part 1: Day 1 through Day 5; Part 2: Day 1 through Day 26 | 
| Number of participants with abnormal vital signs: HR | Abnormal heart rate (beats/minute) | Part 1: Day 1 through Day 5; Part 2: Day 1 through Day 26 | 
| Number of participants with abnormal vital signs: Temp | Abnormal body temperature (Celsius) | Part 1: Day 1 through Day 5; Part 2: Day 1 through Day 26 | 
| Number of participants with abnormal vital signs: RR | Abnormal respiratory rate (breaths/minute) | Part 1: Day 1 through Day 5; Part 2: Day 1 through Day 26 | 
| Number of participants with abnormal physical exams | Physical exams will include evaluation of general appearance, head, neck, thyroid, eyes, ears, nose and throat, respiratory, cardiovascular, abdomen, dermatological, genitourinary, musculoskeletal and neurological systems | Part 1: Day 1 through Day 5; Part 2: Day 1 through Day 26 | 
| Assess PK parameters for single (Part 1) and multiple (Part 2) SC doses of PDM608 in healthy volunteers. | Analysis of PDM608 plasma concentration data will be performed using PK parameters. | Part 1: Day 1 through Day 5; Part 2: Day 1 through Day 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess immunogenicity following single and multiple doses of PDM608 | Incidence of ADA in blood | Part 1: Day 1 through Day 22; Part 2: Day 1 through Day 60 |