A Study of Weekly Subcutaneous Injections of SER-214 in Subjects With Parkinson's Disease (PD), to Determine the Safety, Tolerability and Pharmacokinetic (PK) Profile of SER-214

NCT02579473 | Unknown Phase 1 DMC

• 1 other identifier: SER-214 Ia
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 4

Brief Summary

SER-214 is a poly (2-ethyl-2oxazoline)(POZ) polymer conjugate of rotigotine, a potent dopamine agonist that has high affinity for the subclass of dopamine receptors in the brain that mediate dopamine signaling. SER-214 will be administered subcutaneously once a week via a standard 1 mL insulin syringe to determine the safety, tolerability and pharmacokinetic (PK) profile of released rotigotine and POZ-conjugate. Subjects in this study are eligible if they have early, stable or untreated Parkinson's disease and are still experiencing motor fluctuations.

Conditions

Parkinson's Disease

Keywords

Continuous dopaminergic stimulation

Outcome Measures

Primary Outcomes (6)

• Safety - Adverse Events and Serious Adverse Events

  Change from Screening in frequency of adverse events (AEs) and serious adverse events (SAEs) at the Final Safety Visit

  From initial sc dose of SER-214 up to six weeks of follow-up

• Percentage of patients in each cohort who discontinued therapy due to any adverse events {Tolerability}

  Percentage of patients in each cohort who discontinued therapy due to any adverse events will be used as an assessment of tolerability

  From initial sc dose of SER-214 up to six weeks of follow-up

• Safety - Vital Signs

  Change from Screening in assessment of vital signs (pulse, blood pressure) at each study visit and Final Safety Visit

  From initial sc dose of SER-214 up to six weeks of follow-up

• Safety - Abnormal Laboratory Results

  Change from Screening in number of participants with laboratory test values of potential clinical importance

  From initial sc dose of SER-214 up to six weeks of follow-up

• Safety - Treatment-Emergent Adverse Events

  Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to \[study drug\] will be assessed by the investigator (Yes/No).

  From initial sc dose of SER-214 up to six weeks of follow-up

• Safety - ECG Changes

  Change from Screening in assessment of electrocardiogram (ECG) parameters at each injection visit

  From initial sc dose of SER-214 up to six weeks of follow-up

Secondary Outcomes (9)

• Fluctuation index

  On injection days plasma samples will be taken at time 0, 1, 2, 4 and 8 hours

• Maximum plasma concentration [C(max)]

  On injection days plasma samples will be taken at time 0, 1, 2, 4 and 8 hours

• Time to maximum concentration [T(max)]

  On injection days plasma samples will be taken at time 0, 1, 2, 4 and 8 hours

• Dose-adjusted area under the curve (AUC)

  On injection days plasma samples will be taken at time 0, 1, 2, 4 and 8 hours

• Unified Parkinson's Disease Rating Scale

  From Screening up to six weeks of follow-up

Study Arms (4)

Cohort 0

EXPERIMENTAL

Subjects in Cohort 0 will receive a single subcutaneous injection of 20 mg SER-214, followed by a two week wash-out period, to determine safety, tolerability and PK and terminal "wash-out" of rotigotine and pro-drug SER-214.

Drug: SER-214

Cohort 1

EXPERIMENTAL

Subjects in Cohort 1 will receive a single SC injection of 50 mg SER-214 at the beginning of each week for two consecutive weeks, followed by a two week wash-out period, to determine safety, tolerability and PK and terminal "wash-out" of rotigotine and pro-drug SER-214.

Drug: SER-214

Cohort 2

EXPERIMENTAL

Subjects in Cohort 2 will receive a single SC injection of 50 mg SER-214 at the beginning of week one, followed by a weekly SC injection of 100 mg SER-214 for two consecutive weeks, followed by a two week wash-out period, to determine safety, tolerability and PK and terminal "wash-out" of rotigotine and pro-drug SER-214.

Drug: SER-214

Cohort 3

EXPERIMENTAL

Subjects in Cohort 3 will receive a single SC injection of 50 mg SER-214 at the beginning of week one, followed by a single SC injection of 100 mg SER-214 at the beginning of week two, followed by a single SC injection of 200 mg SER-214 for two consecutive weeks, followed by a two week wash-out period, to determine PK and terminal "wash-out" PK of rotigotine and pro-drug SER-214.

Drug: SER-214

Interventions

SER-214 DRUG

SER-214 is a poly(2-ethyl-oxazoline) (POZ) polymer conjugate of the potent dopamine agonist rotigotine that is designed to provide continuous drug delivery following a single weekly injection

Also known as: POZ-rotigotine

Cohort 0; Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male subjects 40-80 years of age inclusive
• A diagnosis of idiopathic Parkinson's disease (PD) consistent with UK brain bank criteria
• De novo PD patients and those on a stable regimen of anti-Parkinson's drugs for at least 4weeks prior to screening including anticholingerics, amantadine, MAO-B inhibitors, COMT inhibitors or levodopa, but not dopamine agonists
• Free of clinically significant motor complications as determined by the investigator
• Ability to complete up to four weeks of dosing once per week with two weeks of terminal "wash-out" PK
• Ability to return to the clinic for blood sampling, clinical and laboratory assessment on scheduled days, based upon cohort
• Mini Mental State Exam (MMSE) \> 26
• Women of child-bearing potential (WOCBP) must use a reliable method of contraception (e.g., oral contraceptive or long-term injectable or implantable hormonal contraceptive, double-barrier methods \[such as condom plus diaphragm, condom plus spermicidal foam, condom plus sponge\], or intra-uterine devices), and must have a negative serum pregnancy test at Screening and negative urine pregnancy test at baseline
• Willing and able to comply with the study requirements including follow-up
• Provide written informed consent
• Cognitively intact sufficient to understand and provide informed consent
• Approved by a central Eligibility Monitoring Committee (EMC) confirmed by EMC signature on the Enrollment Authorization Form (EAF)

You may not qualify if:

• Subject has previously participated in this study.
• Myocardial infarction within the past six months from screening
• Ischemic stroke or transient ischemic event within the past two years from screening
• Known sensitivity to dopamine agonists including nausea/vomiting, orthostatic hypotension, excessive sleep or impulse control disorder
• Any major organ disease that substantially impairs life expectancy
• History of cancer, other than basal cell carcinoma, within the past 10 years or subjects with any laboratory or physical exam or diagnostic procedure finding suggestive of current malignancy
• Subjects who are known to be immunosuppressed or are receiving chronic treatment with immunosuppressive drugs
• Subject with an atypical or secondary Parkinsonian (e.g., due to drugs, metabolic neurogenetic disorders, encephalitis, cerebrovascular disease or degenerative disease)
• Any clinically significant medical, surgical, or psychiatric condition, laboratory value, or concomitant medication which, in the opinion of the Investigator, makes the subject unsuitable for study entry or potentially unable to complete all aspects of the study.
• Subject has moderate renal impairment (creatine \> 2.5)
• Subject has moderate (Child-Pugh categorization B, score 7-9) or severe (Child-Pugh categorization C, score 10-15) hepatic impairment.
• Subject has a lifetime history of suicide attempt (including an active attempt, interrupted attempt or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response ('Yes') to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (CSSRS) at Screening
• Subject has known hypersensitivity to rotigotine or to any components or excipients of the study drug
• Subject has a history of psychosis or hallucinations within the previous 12 months
• Subject has received an investigational drug within 30 days of screening or is currently participating in an investigational drug or investigational device trial

Sponsors & Collaborators

• Serina Therapeutics: lead

Study Sites (4)

University of Alabama Birmingham

Birmingham, Alabama, 35233, United States

Location

MD Clinical

Hallandale, Florida, 33009, United States

Location

Georgia Regents University

Augusta, Georgia, 30912, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Eskow Jaunarajs KL, Standaert DG, Viegas TX, Bentley MD, Fang Z, Dizman B, Yoon K, Weimer R, Ravenscroft P, Johnston TH, Hill MP, Brotchie JM, Moreadith RW. Rotigotine polyoxazoline conjugate SER-214 provides robust and sustained antiparkinsonian benefit. Mov Disord. 2013 Oct;28(12):1675-82. doi: 10.1002/mds.25625. Epub 2013 Sep 3.

  PMID: 24014074 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• David G Standaert, MD, PhD

  Univeristy of Alabama-Birmingham School of Medicine, Division of Neurology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2015
• First Posted: October 19, 2015
• Study Start: January 1, 2016
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: April 11, 2023

Record last verified: 2022-10

Locations

US (4)