A Randomized, Double-Blind, Placebo-Controlled Trial of IkT-148009 in Untreated Parkinson's Disease

Parkinson Disease Clinical Trial

Official title:

A Phase 2 Study of IkT-148009 in Untreated Parkinson's Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05424276
• Other study ID #: IkT-148009-201
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 15, 2023
• Est. completion date: January 1, 2025

Study information

• Verified date: November 2023
• Source: Inhibikase Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study investigates the safety and tolerability of drug IkT-148009 in untreated Parkinson's disease volunteers (30 to 80 years old). It also looks at the pharmacokinetics of IkT-148009 in the body and evaluates the effect of IkT-148009 on motor and non-motor features of the disease. This 12 week study is designed to be 3:1 randomized across 3 doses of IkT-148009 or placebo. Each participant will self-administer one of 3 doses or placebo of IkT-148009 once daily (QD) with food for 12 weeks. For more information, visit our website: www.the201trial.com

Description:

This is a 12-Week, randomized, double-blind, multi-center, placebo-controlled dose-ranging clinical trial of three IkT 148009 doses in patients with untreated PD designed to assess safety, tolerability, and pharmacokinetics of IkT-148009, an oral, once daily c-Abl tyrosine kinase inhibitor. Secondary and exploratory assessments will evaluate the effect of IkT-148009 on motor and non-motor features of the disease. 120 participants are anticipated to be enrolled at up to 34 sites across the US.

Participants will undergo screening to evaluate their eligibility to participate in the study to include evaluation of Parkinson's diagnosis, vital signs, blood chemistry, hematology and urinalysis and complete listing of concomitant medications. An Enrollment Authorization Committee (EAC) will be responsible for reviewing screening data and confirming the eligibility and suitability of participants. Those selected will be enrolled and randomized to one of three active IkT-148009 arms (50/100/200 mg) or a placebo arm (1:1:1:1). All clinical staff, study investigators, and participants will be blinded to study assignments throughout the trial.

A Data Safety Monitoring Committee (DSMB) will evaluate all available safety, tolerability, and PK and Parkinson's disease-related data for each cohort on a monthly to quarterly basis. Adverse event reporting will be evaluated in real-time.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: January 1, 2025
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

Inclusion Criteria

1. Participants who are diagnosed with PD consistent with UK Brain Bank criteria and MDS Research Criteria; must include bradykinesia with sequence effect and motor asymmetry.

2. Receiving no anti-parkinsonian therapy

3. Modified Hoehn/Yahr Stage < 3.0

4. Montreal Cognitive Assessment = 24

5. Patient expected to be able to participate in trial without need for additional anti-parkinsonian therapy

Sex and Contraceptive/Barrier Requirements:

1. Male participants must agree to practice an acceptable method of highly effective birth control from the screening visit, while on study and for 30 days after receiving the last dose of study drug. Highly effective methods of birth control include sexual abstinence, vasectomy, or a condom with spermicide (men) in combination with their partner's highly effective method.

2. Female participants of childbearing potential and male participants with female partners of childbearing potential must agree to either remain abstinent or use adequate and reliable contraception throughout the study and at least 30 days after the last dose of study drug has been taken.

Informed Consent:

1. Capable of giving signed ICF as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Other Inclusions:

1. Approved as an appropriate and suitable candidate by the EAC.

Exclusion Criteria

1. Diagnosis/suspicion of secondary or atypical parkinsonism

2. Previous procedure or surgery for PD, or anticipation of these during the study

3. High likelihood of needing anti-parkinsonian treatment over the study period, in the opinion of the investigator

4. Clinically significant orthostatic hypotension

5. Clinically significant hallucinations requiring antipsychotic use in the 12 months prior to Screening

6. Clinically significant medical, surgical, psychiatric, or laboratory abnormalities in the judgement of the treating investigator or the EAC

Prior/Concomitant Therapy:

1. Past treatment with levodopa, dopaminergic agonists, monoamine oxidase-B inhibitors, supplements containing levodopa (i.e. Mucana pruriens), or A2A antagonists for more than 28 days, or treatment with any of these medications or supplements within 28 days prior to screening

2. Past treatment with irreversible monoamine oxidase-B inhibitors (e.g., selegiline) for more than 28 days; must be discontinued for at least 90 days before screening

3. Currently receiving moderate or strong Cytochrome P450 (CYP) 3A4/5 inducers or CYP3A4/5 inhibitors (except for topical administration)

4. Currently receiving any antipsychotic, metoclopramide, reserpine, or amphetamine.

Prior/Concurrent Clinical Study Experience:

1. Current participation in another investigational clinical trial and/or receipt of any investigational medication within 90 days prior to screening

2. Previous randomization into this or another IkT-148009 study

Diagnostic Assessments:

1. Active suicidal ideation within one year prior to screening visit, as determined by the Columbia Suicide Rating Scale (answer of "yes" on question 4 or 5)

2. Current diagnosis or history of substance abuse (excluding nicotine or caffeine) by Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria

3. Medical or recreational use of marijuana in the 3 months prior to the screening visit

4. Any social or behavioral reason that would preclude completion of the study, in the judgement of the investigator

5. Any skin condition that would interfere with obtaining adequate samples

6. Evidence of advanced, age-related macular degeneration (neovascular or geographic atrophy) or intermediate macular degeneration as defined by Beckman classification (Large drusen > 125 um and/or any AMD pigmentary abnormalities). Evidence of retina/choroid neovascularization from any cause. Evidence of central serous retinopathy.

7. Abnormal amylase and/or lipase at screening (may be repeated during screening period)

8. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 2.5 times the upper limit of normal (ULN)

9. Significant renal impairment as determined by the following criteria:

• Creatinine clearance (CrCL) less than or equal to 60 mL/min for subjects < 65 years of age

• Creatine clearance (CrCL) greater than or equal to 55 mL/min and the absence of proteinuria or hematuria for subjects = 65 years of age

10. Currently lactating, pregnant or planning on becoming pregnant during the study

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• IkT-148009
Oral administration gelatin capsule
• Placebo
Oral administration gelatin capsule

Locations

Country	Name	City	State
United States	Neurologist	Boca Raton	Florida
United States	Neurology	Columbus	Ohio
United States	Neurology	Durham	North Carolina
United States	Neurology	Farmington Hills	Michigan
United States	Neurology	Foxboro	Massachusetts
United States	Neurology	Frisco	Texas
United States	Neurology	Golden Valley	Minnesota
United States	Neurology	Houston	Texas
United States	Neurology	Kirkland	Washington
United States	Neurology	Little Rock	Arkansas
United States	Neurology	Madison	Wisconsin
United States	Neurology	Memphis	Tennessee
United States	Neurology	Miami	Florida
United States	Neurology	Milwaukee	Wisconsin
United States	Neurology	Naples	Florida
United States	Neurology	Nashville	Tennessee
United States	Neurology	Port Royal	South Carolina
United States	Neurology	Portland	Oregon
United States	Neurology	Raleigh	North Carolina
United States	Neurology	Reseda	California
United States	Neurology	Round Rock	Texas
United States	Neurology	Scottsdale	Arizona
United States	Neurology	South Dartmouth	Massachusetts
United States	Neurology	Stamford	Connecticut
United States	Neurology	Tampa	Florida
United States	Neurology	Tampa	Florida
United States	Neurology	Tulsa	Oklahoma
United States	Neurology	West Long Branch	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Inhibikase Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Phosphorylated alpha-synuclein in cerebrospinal fluid (CSF)	Detection of the presence or absence of phosphorylated alpha-synuclein in CSF	Change from Baseline to Week 12
Other	Phosphorylated alpha-synuclein in skin	Detection of the presence or absence of phosphorylated alpha-synuclein in peripheral nerve biopsy in skin	Change from Baseline to Week 12
Primary	Incidence and temporal profile of treatment-emergent adverse events (TEAEs) evaluated by type/nature, severity/intensity, seriousness, and relationship to study intervention		Day 1 through week 16
Primary	Proportion of those randomized in each dosing cohort who discontinued the assigned regimen		Day 1 through week 12
Secondary	Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II + III	Higher scores mean worse outcome from 0 to 52	Change from Baseline to Week 12
Secondary	Patient Global Impression-Severity (PGI-S)	Scale varies from None to Very Severe	Change from Baseline to Week 12
Secondary	Clinician Global Impression of Severity (CGI-S)	Higher scores mean worse outcome between 1 and 7.	Change from Baseline to Week 12
Secondary	Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I	Higher scores mean worse outcome from 0 to 52.	Change from Baseline to Week 12
Secondary	Non-Motor Symptom Scale (NMSS)	Higher scores mean worse outcome from 0 to 360.	Change from Baseline to Week 12
Secondary	Complete Spontaneous Bowel Movement (CSBM)	A value < 3 implies constipation	Change from Baseline to Week 12
Secondary	Epworth Sleepiness Scale (ESS)	Higher score means worse outcome from 0 to 24.	Change from Baseline to Week 12
Secondary	Schwab and England Activities of Daily Living (SE-ADL) Scale	Higher score means worse outcome from 0% to 100%	Change from Baseline to Week 12
Secondary	Parkinson's Disease Questionnaire (PDQ-39)	Higher scores mean worse outcome from 0 to 100.	Change from Baseline to Week 12
Secondary	Patient Assessment of Upper Gastrointestinal Disorders Severity Index (PAGI-SYM)	Higher score means worse outcome from 0 to 100.	Change from Baseline to Week 12
Secondary	Patient Assessment of Constipation Quality of Life (PAC-QOL)	Higher score means worse outcome from 0 to 150.	Change from Baseline to Week 12
Secondary	Patient Assessment of Gastrointestinal Disorders Severity Quality of Life (PAGI- QOL)	Higher score means worse outcome from 0 to 150.	Change from Baseline to Week 12