SAD Study in Patients With Parkinson's Disease and Motor Fluctuations

A Randomized, Placebo-Controlled, Single Ascending Dose (SAD) Study to Assess the Safety, Tolerability, and Pharmacokinetics of SER-252 in Patients With Parkinson's Disease and Motor Fluctuations

This is a randomized, placebo-controlled, single ascending dose (SAD) study of SER-252 in participants with Parkinson's Disease (PD) and motor fluctuations.

Study Overview

• Status: Recruiting
• Conditions: Advanced Parkinson's Disease; PARKINSON DISEASE (Disorder)
• Intervention / Treatment: Drug: SER-252 (PEOZ-apomorphine); Device: enFuse

Detailed Description

Participants will be enrolled into five sequential groups. Each group will include eight participants, dosed in a 3:1 ratio (six receiving SER-252 and two receiving placebo). All participants will receive a single dose of study drug. Each successive group will receive a higher dose level of SER-252 than the previous group. Some participants will receive a subcutaneous injection of SER-252, while others will receive placebo.

Single ascending dose (SAD) cohorts will utilize a sentinel dosing approach, with subsequent dosing conducted in a staggered manner if ongoing safety and tolerability assessments allow. In each cohort, the first two participants (one receiving SER-252 and one receiving placebo) will be dosed separately ahead of the remaining participants. These sentinel participants will be observed and evaluated as described in the protocol before dosing proceeds for the rest of the cohort.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Randall Moreadith, MD, PhD; Phone Number: (256) 783-7649; Email: rmoreadith@serinatherapeutics.com

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • CMAX
      • Principal Investigator: Michele de Sciscio, MD
      • Contact: CMAX Clinical Research Group; Phone Number: 61 8 7088 7900; Email: parkinsonsC16625@cmax.com.au
  • Victoria
    • Melbourne, Victoria, Australia, 3170
      • Recruiting
      • Monash
      • Contact: Monash House Research Centre; Phone Number: +61 3 8394 0700; Email: research@monashhouse.com.au
      • Principal Investigator: Purwa Joshi, MD
• United States
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Not yet recruiting
      • Rocky Mountain Clinical Research
      • Contact: Heather Fasczewski; Phone Number: (248) 957-8940; Email: Heather.Fasczewski@questri.com
      • Principal Investigator: Meagan Salinas, MD
  • Florida
    • Hallandale, Florida, United States, 33009
      • Recruiting
      • Velocity Clinical Research
      • Principal Investigator: Beth Safirstein, MD
      • Contact: William Torres; Phone Number: (954) 455-5757; Email: wtorres@velocityclinical.com
    • Maitland, Florida, United States, 32751
      • Recruiting
      • K2 Medical Research LLC
      • Principal Investigator: Sheila Baez-Torres, MD
  • Michigan
    • Farmington Hills, Michigan, United States, 28555
      • Recruiting
      • Quest Research Institute
      • Contact: Heather Fasczewski; Phone Number: (248) 957-8940; Email: Heather.Fasczewski@questri.com
      • Principal Investigator: Aaron Ellenbogan, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria

1. Female or male participants 40-80 years of age, inclusive, at the time of screening
2. Diagnosis of idiopathic Parkinson's disease consistent with UK Brain Bank and MDS Research Criteria; must include bradykinesia with sequence effect, motor asymmetry if no rest tremor, and a reliable, visible response to levodopa
3. On a stable regimen of anti-Parkinsonian medication for at least 4 weeks prior to Screening; MAOBIs must be stable for at least 12 weeks prior to Screening
4. Routine early-morning OFF, corroborated by investigator interview at Screening
5. Presence of a total daily OFF time duration of ≥2 hours during the waking day based on participant self-assessment and Investigator's judgment
6. *Hoehn and Yahr scale ≤ 3 in the ON state during screening (*part of the MDS- UPDRS Part III assessment)
7. Levodopa administration at least 4 times daily (immediate or extended release) or three times daily (Rytary or Crexont)
8. Ability to return to the clinic for blood sampling, clinical and laboratory assessment on scheduled days, based upon cohort
9. Montreal Cognitive Assessment ≥ 24
10. Women of child-bearing potential (WOCBP) who are sexually active with a male partner must use a reliable method of contraception from the time of consent through at least 3 months after the last dose of study medication. Reliable methods of contraception include oral contraceptive or long-term injectable or implantable hormonal contraceptive, or intra-uterine devices when used in combination with male condoms, and must have a negative serum pregnancy test at Screening and negative urine pregnancy test at baseline. Males who are sexually active and whose partners are females of childbearing potential must agree to use male condoms from the time of consent through 3 months after administration of the last dose of study drug, and their partners must be willing to use a highly effective method of contraception from screening through 3 months after administration of the last dose of study drug.
11. Willing and able to comply with all study activities and requirements, including safety follow-up
12. Provide written informed consent
13. Approved by a central Enrollment Authorization Committee (EAC)

Exclusion criteria

1. Diagnosis of secondary or atypical parkinsonism
2. Any previous procedure or therapy designed to provide continuous levodopa or stimulation of dopaminergic tone (i.e., Duopa, apomorphine), surgery for PD (i.e., DBS), or anticipation of these during the study
3. History of exclusively diphasic, OFF state, myoclonic or dystonic dyskinesias without peak-dose choreiform dyskinesia
4. Clinically debilitating motor complications as determined by the principal investigator or delegate (severe, disabling dyskinesias or severe OFF)
5. Participant inability to differentiate motor states (OFF/ON/ON with mild/moderate/severe dyskinesias) after training
6. Clinically significant orthostatic hypotension (consistently symptomatic or requires medication)
7. Clinically significant hallucinations requiring antipsychotic use
8. Clinically significant medical, surgical, psychiatric, or laboratory abnormalities that in the judgment of the principal investigator or delegate would preclude adequate participation or completion of the study
9. Clinically significant ECG abnormalities at Screening
10. Prolonged Fridericia-corrected QT (QTcF) interval on ECG at Screening (defined as a QTcF interval of >450 msec for males and 470 for females)

11. Clinically significant heart disease within 2 years of Screening, defined as follows:

    A. Significant cardiac event within 12 weeks prior to Screening (e.g., admission for myocardial infarction, unstable angina, or decompensated heart failure), angina pectoris or episode of congestive heart failure with symptoms > grade 2 New York Heart Association classification, or presence of cardiac disease that in the opinion of the investigator increases the risk of ventricular arrhythmia B. History of complex arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia) that was symptomatic or required treatment (Common Terminology Criteria for Adverse Events grade 3) C. Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia D. Symptomatic bradycardia, sick sinus syndrome or atrioventricular block greater than first degree in the absence of a pacemaker E. Unexplained syncope F. Brugada syndrome G. Hypertrophic cardiomyopathy

12. Active major depressive disorder or history of clinically significant impulse control disorder, in the opinion of the Principal Investigator or delegate, or EAC.

    Note: Participants receiving treatment for depression with antidepressants may be enrolled if they have been on a stable daily dose of the antidepressant for at least 8 weeks prior to Screening.

13. Has active suicidal ideation within one year prior to Screening as determined by the C-SSRS (answer of "yes" on questions 4 or 5) or attempted suicide within the last 5 years
14. Has been diagnosed with or history of a substance-related disorder (excluding nicotine and caffeine), including alcohol-related disorder by DSM-V criteria, during the 12 months prior to Screening
15. Tests positive at Screening for drugs of abuse (amphetamines (AMP), barbiturates (BAR), benzodiazepines (BZO), cocaine (COC), opiates (OPI), methamphetamines (MET), methadone (MTD), Phencyclidine (PCP), tetrahydrocannabinol (THC), tricyclic antidepressants (TCA)) Note: does not exclude patients on physician-prescribed medications.
16. Has ALT or AST levels greater than 2.5 times the ULN or bilirubin > 2.0 mg/dL, or > 34.2 µmol/L
17. Significant renal impairment as determined by eGFR, using Cockcroft-Gault method, less than or equal to 55 ml/min or serum creatinine >2.0 mg/dL or >177 µmol/L
18. Has a positive test result for HBsAg, HCV antibody, or HIV infection at Screening
19. Currently lactating or pregnant or planning to become pregnant during the study.
20. Previous intolerance of apomorphine
21. Currently participating in or has participated in another investigational study within the last 30 days or 5 half-lives, or 90 days for biologics

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SER-252 (PEOZ-apomorphine); SER-252 (PEOZ-apomorphine) Single subcutaneous dose delivered by enFuse® on body device; weight-based apomorphine equivalents/kg by cohort: 0.48, 0.60, 0.75, 0.90, 1.0 mg-eq/kg. SER-252 drug product consists of 20mg lyophilized apomorphine equivalent in SER-252 drug substance in a sterile vial for reconstitution with a diluent product containing 15mM acetate buffer at pH 6.0 and 7% trehalose to maintain final pH and isotonicity in the reconstituted product.	Drug: SER-252 (PEOZ-apomorphine); SER-252 drug product consists of 20mg lyophilized apomorphine equivalent in SER-252 drug substance in a sterile vial for reconstitution with a diluent product containing 15mM acetate buffer at pH 6.0 and 7% trehalose to maintain final pH and isotonicity in the reconstituted product.; Device: enFuse; The enFuse® device is a sterile, non-pyrogenic, user-filled, single-use, fixed-dose subcutaneous dose delivery system.
Placebo Comparator: Diluent Product; The SER-252 Diluent Product, 12 ml size will be used as the placebo formulation. The appearance of the diluent product is clear and colorless. Matching subcutaneous administration by the same device.	Device: enFuse; The enFuse® device is a sterile, non-pyrogenic, user-filled, single-use, fixed-dose subcutaneous dose delivery system.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Temporal Profile of Treatment-Emergent Adverse Events (TEAEs)	Proportion of participants with TEAEs (new onset or worsening) and temporal profile post-dose; TEAEs summarized by type/nature, severity/intensity, seriousness, and relationship to study treatment per protocol.	From first dose through Day 21 (7 days after the Day 14 end-of-participation visit).
Incidence of Moderate or Severe TEAEs Related to Study Intervention	Proportion of participants experiencing moderate or severe TEAEs related to study intervention (including possibly and probably related).	From first dose through Day 21 (7 days after the Day 14 end-of-participation visit).
Incidence of Serious Adverse Events (SAEs), including suicidality by Columbia-Suicide Severity Rating Scale (C-SSRS)	Proportion of participants with SAEs (ICH-GCP), including suicidality identified via C-SSRS	From first dose through Day 44 (30 days after the Day 14 end-of-participation visit).
Change from Baseline in Vital Signs	Mean change from baseline in systolic and diastolic blood pressure, heart rate, respiratory rate, and temperature.	Baseline to Day 8 (with Day 14 follow-up vitals also collected)
Area under the concentration-time curve (AUC0-24, AUC0-96, AUC0-∞)	AUC from time zero to infinity hours post-dose, calculated using noncompartmental methods (ng·h/mL)	Day 1 through Day 8 (0-168 hours post-dose)
Change from Baseline in Corrected QT Interval (QTcF)	Mean change from baseline in Fridericia-corrected QT interval (QTcF) from 12-lead ECGs. (millisecond (ms))	Baseline to Day 8 (with Day 14 safety follow-up ECGs).
Time to Maximum Plasma Concentration (Tmax)	Observed time to reach Cmax (first occurrence), based on the protocol-defined sampling schedule. (hours)	Day 1 through Day 8 (0-168 hours post-dose).
Change from Baseline in Clinical Laboratory Parameters	Mean change from baseline in hematology and serum chemistry panels.	Baseline to Day 8 (laboratories at safety follow-up only if needed to follow up abnormalities).
Fluctuation Index (FI)	FI calculated as (Cmax - Cmin) / Cavg over 0-168 hours.	Day 1 through Day 8 (0-168 hours)
Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale (QUIP-RS)	Incidence and severity of impulsive-compulsive behaviors assessed by QUIP-RS. The QUIP-RS total score ranges 0-112, with higher scores indicating more severe symptoms.	Screening/Day -1 and Day 8.
Trough Concentration (Ctrough)	Observed plasma concentrations at nominal trough timepoints: 24, 48, 72, 96, 120, 144, and 168 hours post-dose. (ng/mL)	Days 2-8 (24-168 hours post-dose).
Coefficient of Variation (CV%) for Exposure	Between-participant variability in key PK parameters (e.g., Cmax, AUC), calculated as 100 × (SD / mean).	Day 1 through Day 8 (0-168 hours).
Distributional Half-Life (h)	Distributional half-life estimated from the distribution phase of the concentration-time profile, when model assumptions permit. (hours)	Day 1 through Day 8
Maximum Plasma Concentration (Cmax)	Cmax of SER-252-derived apomorphine following a single subcutaneous dose, derived from plasma concentrations collected at: pre-dose (0), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12 hours on Day 1; and 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, and 168 hours post-dose.(ng/mL)	Day 1 through Day 8 (0-168 hours post-dose)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Efficacy Endpoint: Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II	MDS-UPDRS Part II Change from baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II score. The MDS-UPDRS Part II assesses motor aspects of daily living on a scale from 0 to 52, with higher scores indicating greater impairment.	Change from Baseline at Day 8
Exploratory Efficacy Endpoint: Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III - Change from Baseline at 4 Hours	Change from baseline in the MDS-UPDRS Part III (motor examination) total score at 4 hours post-dose. The MDS-UPDRS Part III ranges from 0 to 132, with higher scores indicating greater motor impairment. Time Frame: Baseline to 4 hours post-dose.	Baseline to 4 hours post dose
Exploratory Efficacy Endpoint: Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III - Maximum Daily Change from Baseline	Maximum (most extreme) change from baseline in MDS-UPDRS Part III total score observed across the following post-dose timepoints: 1, 2, 3, 4, 6, 9, and 12 hours. Scale range: 0-132, higher scores = worse.	Baseline to 12 hours post-dose
Exploratory Efficacy Endpoint: Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III - Area Under the Curve (AUC)	AUC of change from baseline in MDS-UPDRS Part III total score over the following timepoints: baseline and 1, 2, 3, 4, 6, 9, and 12 hours post-dose. Positive AUC values indicate net worsening; negative values indicate net improvement over time. Scale range: 0-132, higher scores = worse. Time Frame: Baseline to 12 hours post-dose.	Baseline to 12 hours post-dose

Collaborators and Investigators

• Sponsor: Serina Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2026
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2027

Study Registration Dates

• First Submitted: February 5, 2026
• First Submitted That Met QC Criteria: February 12, 2026
• First Posted (Actual): February 20, 2026

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: advanced Parkinson's Disease
• 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: SER-252-1b

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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