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

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

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

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Placebo; Drug: IkT-148009 (risvodetinib)

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Neurology
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Neurology
  • California
    • Reseda, California, United States, 91335
      • Neurology
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • Neurology
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Neurologist
    • Miami, Florida, United States, 33136
      • Neurology
    • Naples, Florida, United States, 34105
      • Neurology
    • Tampa, Florida, United States, 33609
      • Neurology
    • Tampa, Florida, United States, 33613
      • Neurology
  • Massachusetts
    • Foxborough, Massachusetts, United States, 02035
      • Neurology
    • South Dartmouth, Massachusetts, United States, 02747
      • Neurology
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Neurology
  • Minnesota
    • Golden Valley, Minnesota, United States, 55427
      • Neurology
  • New Jersey
    • West Long Branch, New Jersey, United States, 07764
      • Neurology
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Neurology
    • Raleigh, North Carolina, United States, 27607
      • Neurology
  • Ohio
    • Columbus, Ohio, United States, 43221
      • Neurology
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Neurology
  • Oregon
    • Portland, Oregon, United States, 97239
      • Neurology
  • South Carolina
    • Port Royal, South Carolina, United States, 29935
      • Neurology
  • Tennessee
    • Memphis, Tennessee, United States, 38137
      • Neurology
    • Nashville, Tennessee, United States, 37232
      • Neurology
  • Texas
    • Frisco, Texas, United States, 75035
      • Neurology
    • Houston, Texas, United States, 77030
      • Neurology
    • Round Rock, Texas, United States, 78681
      • Neurology
  • Washington
    • Kirkland, Washington, United States, 98034
      • Neurology
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Neurology
    • Milwaukee, Wisconsin, United States, 53226
      • Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 50mg IkT-148009 (risvodetinib); This arm consisted of participants treated with the 50mg dose of risvodetinib.	Drug: IkT-148009 (risvodetinib); Oral administration gelatin capsule
Experimental: 100mg IkT-148009 (risvodetinib); This arm consisted of participants treated with the 100mg dose of risvodetinib.	Drug: IkT-148009 (risvodetinib); Oral administration gelatin capsule
Experimental: 200mg IkT-148009 (risvodetinib); This arm consisted of participants treated with the 200mg dose of risvodetinib.	Drug: IkT-148009 (risvodetinib); Oral administration gelatin capsule
Placebo Comparator: Placebo; This arm consisted of participants treated with placebo.	Drug: Placebo; Oral administration gelatin capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Treatment-emergent Adverse Events (TEAEs)	Baseline to 12 weeks
Proportion of Those Randomized in Each Dosing Cohort Who Discontinued the Assigned Regimen Due to an Adverse Event	Baseline to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LS Mean of Change From Baseline in MDS-UPDRS Part II+III From a Mixed Model for Repeated Measures	Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Parts II and III reflect assessments covering activites of daily living as reported by the participant (Part II) as well as a clinicians assessment of motor abilities (Part III). Part II consists of 13 items with total scores ranging from 0 to 52 while Part III consists of 18 items with total scores range from 0 to 132. Each item is scored 0 (normal) to 4 (severe). The sum of Parts 2 and 3 have a score range of 0 to 184 (31 total items). An increase in sum of Parts 2 and 3 relative to baseline represents a worsening of the participant's Parkinson's disease	Baseline to Week 12
LS Mean of Change From Baseline in PDQ-39 From a Mixed Model for Repeated Measures	Parkinson's Disease Questionnaire (PDQ) consists of 39 questions evaluating activities of daily living. Participants rate each question on a 5 point scale (0 to 4), . The PDQ-39 score ranges from 0 to 100 with higher score representing more advanced disease.	Change from Baseline to Week 12
LS Mean of Change From Baseline in PGI-S From a Mixed Model for Repeated Measures	Patient Global Impression - Severity (PGI-S) is participant reported assessment designed to evaluate the severity of their Parkinson's Disease. Scores range from 1 to 4 with 1 considered Normal and 4 considered Severe.	Change from Baseline to Week 12
LS Mean of Change From Baseline in CGI-S From a Mixed Model for Repeated Measures	Clinician Global Impression - Severity (CGI-S) is clinician reported assessment designed to evaluate the severity of a participants Parkinson's disease. Scores range from 1 to 7 with 1 considered "Normal" and 7 considered "Among the most extremely ill patients".	Change from Baseline to Week 12
LS Mean of Change From Baseline in MDS-UPDRS Part II From a Mixed Model for Repeated Measures	Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Part II assesses activities of daily living as reported by the participant. Part II consists of 13 items with a total score ranging from 0 to 52. Each item is scored 0 (normal) to 4 (severe). Higher scores reflect increased severity of disease.	Baseline to 12 weeks
LS Mean of Change From Baseline in MDS-UPDRS Part III From a Mixed Model for Repeated Measures	Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Part III is completed by clinician and assesses a participants motor function. Part III consists of 18 items with a total score ranging from 0 to 132. Each item is scored 0 (normal) to 4 (severe). Higher scores reflect increased severity of disease.	Baseline to 12 weeks
LS Mean of Change From Baseline in MDS-UPDRS Part I From a Mixed Model for Repeated Measures	Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Part I assesses non-motor experiences of daily living. Part I is made up of two section with one rated by the investigator and another completed by the participant. Part I consists of 13 items with a total score ranging from 0 to 52. Each item is scored 0 (normal) to 4 (severe). Higher scores reflect increased severity of disease.	Change from Baseline to Week 12
LS Mean of Change From Baseline in NMSS From a Mixed Model for Repeated Measures	Non-Motor Symptom Score (NMSS) is a 30 question assessment completed by the clinician designed to evaluate the non-motor symptoms of Parkinson's disease. Scores range from 0 to 360 with higher scores reflect increasing severity of disease	Change from Baseline to Week 12
LS Mean of Change From Baseline in CSBM Score From a Mixed Model for Repeated Measures	The Complete Spontaneous Bowel Movement (CSBM) Diary is a participant-completed paper diary used to record bowel movement activity over a 7-day period. Each entry captures the date and time of the bowel movement, stool consistency (Bristol Stool Form Scale), and whether the bowel movement was spontaneous (no laxative or rescue medication within the previous 24 hours) and complete (a sensation of full evacuation). The weekly CSBM score is calculated as the total number of complete and spontaneous bowel movements recorded during the 7-day period. Rome IV criteria defines constipation as having less than 3 CSBMs per 7 day period. A decrease in CSBM score represents a decrease in bowel function.	Change from Baseline to Week 12
LS Mean of Change From Baseline in ESS From a Mixed Model for Repeated Measures	The Epworth Sleepiness Scale is a self-administered questionnaire that measures a participant's general level of daytime sleepiness. Participants rate their likelihood of dozing off or falling asleep in eight common situations using a 4-point scale from 0 = would never doze to 3 = high chance of dozing. The total ESS score ranges from 0 to 24, with higher scores indicating greater daytime sleepiness.	Change from Baseline to Week 12
LS Mean of Change From Baseline in SE-ADL From a Mixed Model for Repeated Measures	Schwab and England Activies of Daily Living (SE-ADL) is a clinician administered assessment whereby participants assess their ability to complete routine daily activities on a scale from 0 to 100. The score is reported in increments of 10 with 100 representing normal ability to complete daily activities.	Change from Baseline to Week 12
LS Mean of Change From Baseline in PAGI-SYM From a Mixed Model for Repeated Measures	The Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) is a participant-reported questionnaire designed to assess the severity of upper gastrointestinal symptoms over the previous two weeks. The instrument includes 20 items. Each item is rated on a 6-point Likert scale from 0 = none to 5 = very severe, with higher scores indicating greater symptom severity. A total score is calculated as the mean of non-missing item responses.	Change from Baseline to Week 12
LS Mean of Change From Baseline in PAC-QoL From a Mixed Model for Repeated Measures	The Patient Assessment of Constipation Quality of Life (PAC-QOL) is a participant-reported questionnaire that evaluates the impact of constipation and its treatment on quality of life over the previous two weeks. It consists of 28 items. Each item is rated on a 5-point Likert scale from 0 = not at all / very satisfied to 4 = extremely / very dissatisfied, depending on item phrasing. Scores are calculated as the mean of all non-missing items, with higher scores indicating greater negative impact on quality of life.	Change from Baseline to Week 12
LS Mean of Change From Baseline in PAGI-QoL From a Mixed Model for Repeated Measures	The Patient Assessment of Upper Gastrointestinal Disorders Quality of Life (PAGI-QOL) is a validated, participant-reported questionnaire that assesses the impact of upper gastrointestinal symptoms on quality of life over the previous two weeks. The instrument includes 30 items. Each item is rated on a 6-point Likert scale from 0 = none of the time to 5 = all of the time. Scores are calculated as the mean of all non-missing items, with lower scores represent a greater negative impact on a participant's quality of life.	Change from Baseline to Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: ABLi Therapeutics, Inc.
• Investigators: Principal Investigator: Milton Werner, PhD, ABLi Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2023
• Primary Completion (Actual): October 25, 2024
• Study Completion (Actual): September 13, 2025

Study Registration Dates

• First Submitted: June 10, 2022
• First Submitted That Met QC Criteria: June 14, 2022
• First Posted (Actual): June 21, 2022

Study Record Updates

• Last Update Posted (Estimated): November 19, 2025
• Last Update Submitted That Met QC Criteria: November 6, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Untreated Parkinsons 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: IkT-148009-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: End of study
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No