PROSEEK: A Phase 2 Study In Early Parkinson's Disease Patients Evaluating The Safety And Efficacy Of Abl Tyrosine Kinase Inhibition Using K0706

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of K0706 in Subjects With Early Parkinson's Disease

This study consists of 2 parts. Part 1 of the study is conducted to evaluate the efficacy, safety, and tolerability of two doses of K0706 compared to placebo in subjects with early Parkinson's Disease who are not receiving dopaminergic therapy. Part 2 is an optional long term extension study for subjects who have completed week 40 of Part 1

Study Overview

• Status: Terminated
• Conditions: Early Parkinson Disease
• Intervention / Treatment: Drug: K0706; Drug: K0706; Other: placebo

Detailed Description

This study is designed to assess the ability of K0706 to slow the progression of PD. Preclinical animal model data have already demonstrated that K0706 has neuroprotective activity, but further development will require human clinical experience.

This study will also allow determination of safety and tolerability of K0706 over many months in subjects with PD.

• Study Type: Interventional
• Enrollment (Actual): 513
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hungary
  • Buapest
    • Budapest, Buapest, Hungary, 1135
      • Nyiro Gyula Hospital
  • Komarom-Esztergom
    • Tatabánya, Komarom-Esztergom, Hungary, 4032
      • Szent Borbala Korhaz
  • Komárom-Esztergom
    • Esztergom, Komárom-Esztergom, Hungary, 2500
      • VALEOMED Diagnosztikai Központ
  • Pest
    • Kistarcsa, Pest, Hungary, 2143
      • Pest Megyei Flor Ferenc Korhaz
• India
  • Kolkata, India
    • Bangur Institute of Neurosciences & Psychiatry (BINP)
  • New Delhi, India, 110060
    • Sir Ganga Ram Hospital
  • Pune, India, 411004
    • Deenanath Mangeshkar Hospital & Research Center (DMHRC)
  • Hyderabad
    • Panjagutta, Hyderabad, India, 500082
      • Nizam's Institute of Medical Sciences
  • Maharashtra
    • Mumbai, Maharashtra, India, 400026
      • Jaslok Hospital and Research Centre
  • Maharastra
    • Mumbai, Maharastra, India, 400016
      • P.D. Hinduja National Hospital and Medical Care Research Centre
  • New Delhi
    • Vasant Kunj, New Delhi, India, 110070
      • Fortis Flt. Lt. Rajan Dhall Hospital
  • Pune
    • Aundh, Pune, India, 411007
      • Medipoint Hospital
    • Wakad, Pune, India, 411057
      • Lifepoint Multispeciality Hospital Pvt Ltd
  • Punjab
    • Ludhiāna, Punjab, India, 141001
      • Dayanand Medical College & Hospital, Research & Development Centre
  • Telangana
    • Hyderabad, Telangana, India, 500 034
      • Citi neuro centre
  • West Bengal
    • Kolkata, West Bengal, India, 700017
      • Institute of Neurosciences Kolkata
• Poland
  • Warszawa, Poland
    • Mazowiecki Szpital Bródnowski w Warszawie Sp. z o.o.
  • Kujawsko-Pomorskie
    • Toruń, Kujawsko-Pomorskie, Poland, 87-100
      • Nasz Lekarz Przychodnie Medyczne Ośrodek Badań Klinicznych
  • Lodzkie
    • Łódź, Lodzkie, Poland, 90-368
      • SOMED CR
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-097
      • NZOZ Neuromed M. i M. Nastaj Sp. P.
    • Lublin, Lubelskie, Poland, 20-412
      • ETG Lublin
  • Malopolskie
    • Krakow, Malopolskie, Poland, 31-505
      • Krakowska Akademia Neurologii
  • Mazowieckie
    • Sochaczew, Mazowieckie, Poland, 96-500
      • RCMed Oddział w Sochaczewie
    • Warszawa, Mazowieckie, Poland, 00-732
      • SINGUA Sp. Z o.o.
  • Slaskie
    • Katowice, Slaskie, Poland, 40-026
      • C.M. Silmedic Sp. z o.o.
    • Siemianowice Śląskie, Slaskie, Poland, 41-100
      • Neuro-Care - Sp. z o.o. Sp. Komandytowa Ul. Szpitalna 6
  • Wielkopolskie
    • Poznań, Wielkopolskie, Poland, 61-485
      • NZOZ Centrum Medyczne HCP
• Slovakia
  • Banska Bystrica, Slovakia, 974 04
    • MUDr. Beata Dupejova, neurologicka ambulancia s.r.o
  • Spiska Nova Ves
    • Krompachy, Spiska Nova Ves, Slovakia, 5342
      • NEURES, s.r.o.
  • Trencin
    • Dubnica Nad Váhom, Trencin, Slovakia, 018 41
      • Medical Center Konzilium
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08195
    • Hospital Universitari General de Catalunya
  • Barcelona, Spain, 08907
    • Hospital Universitari de Bellvitge (IDIBELL)
  • Girona, Spain, 17190
    • Hospital Universitari de Girona Doctor Josep Trueta
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de las Nieves
  • Madrid, Spain, 28006
    • Hospital Universitario de la Princesa
  • Madrid, Spain, 28040
    • Hospital Quiron Salud
  • Madrid, Spain, 28049
    • Hospital Universitario Ramon y Cajal
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46017
    • Hospital Universitario Dr. Peset
  • Bilbao
    • Barakaldo, Bilbao, Spain, 48903
      • Plaza de Cruces, S/N
  • San Sebastián
    • San Sebastian, San Sebastián, Spain, 20014
      • Policlinica Gipuzkoa
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Xenoscience Inc. - 21st Century Neurology
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences (UAMS) - Movement Disorders Clinic
  • California
    • Los Angeles, California, United States, 90033
      • Keck Hospital of USC
    • Santa Monica, California, United States, 90404
      • Pacific Movement Disorders Center Pacific Neuroscience Institute Providence Saint John's Health Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center Department of Neurology, 7PHC
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research Institute
    • Aventura, Florida, United States, 33180
      • Visionary Investigators Network
    • Boca Raton, Florida, United States, 33486
      • Parkinson's Disease and Movement Disorders Center of Boca Raton, Inc.
    • Maitland, Florida, United States, 32751
      • Neurology Associates PA
    • Miami, Florida, United States, 33176
      • Visionary Investigators Network
    • Port Charlotte, Florida, United States, 33952
      • Medsol Clinical Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center (KUMC)
  • Michigan
    • West Bloomfield, Michigan, United States, 48322
      • Henry Ford West Bloomfield Hospital
  • Minnesota
    • Golden Valley, Minnesota, United States, 55427
      • Struthers Parkinson's Center -Park Nicollet
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University (WUSTL) School of Medicine
  • Nevada
    • Reno, Nevada, United States, 89502
      • Renown Regional Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center (DHMC) Neurology Research
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Robert Wood Johnson Medical School Department of Neurology, Clinical Academic Building (CAB)
    • West Long Branch, New Jersey, United States, 07764
      • Neurology Specialists of Monmouth County, PA
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurologic Institute - Amherst
    • New York, New York, United States, 10021
      • Weill Cornell Medicine Department of Neurology Parkinson's Disease and Movement Disorders Institute
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • The Movement Disorder Clinic of Oklahoma
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Texas
    • El Paso, Texas, United States, 79912
      • Advanced Neurology Epilepsy and Sleep Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Neurological Institute
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine (BCM)- Parkinson's Disease Center and Movement Disorders Clinic (PDCMDC)
    • Round Rock, Texas, United States, 78681
      • Central Texas Neurology Consultants (CTNC)
  • Washington
    • Kirkland, Washington, United States, 98034
      • Evergreen Health
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Part 1:

Inclusion criteria:

1. Males or females aged ≥ 50 years;
2. Body mass index (BMI) greater than 18.5 kg/m2 and less than 45 kg/m2;
3. Diagnosed with "Clinically Probable PD" according to the MDS clinical diagnostic criteria, with documented diagnosis of PD per treating physician's records within three years of the Screening visit. Disease severity according to modified Hoehn & Yahr stage ≤ 2;
4. Projected to not required to start dopaminergic therapy within 9 months from Baseline;

Exclusion criteria:

1. Current, or within 60 days of Screening, use of any prescription, investigational, or over the counter medication for the symptomatic treatment of PD or to slow the progression of PD. Treatment with Monoamine Oxidase B (MAOB) inhibitors will be allowed if the dose is stable for at least 30 days prior to Screening and subjects agree to remain on it for the duration of the study;
2. Prior use of dopaminergic therapy (e.g., levodopa, dopamine agonist, amantadine) for 30 or more days any time in the past;
3. A diagnosis of a significant central or peripheral nervous system disease affecting the subject's cognition or motor function at any time, such as another neurodegenerative disorder, multiple sclerosis or stroke. This does not include transient neurological deficits such as transient ischemic attacks or migraine aura;
4. A diagnosis of a medical condition that could interfere with interpretation of the MDS-UPDRS during the trial (e.g., musculoskeletal disorders);
5. Contraindications to receiving an MRI;
6. Contraindications to receiving a DaT SPECT scan (e.g., hypersensitivity to the active substance, any of the excipients, or iodine) if a new DaT SPECT scan is required for the study;
7. Most recent DaT SPECT scan not compatible with PD (i.e., Scans Without Evidence of Dopaminergic Deficit [SWEDD]) based on a central reading by a study physician;
8. MRI of the brain performed after onset of PD suggestive of secondary Parkinsonism (e.g., subdural hematoma, normal pressure hydrocephalus, or infarcts of the basal ganglia);
9. Severe tremors as defined by a score of "severe" on any of the MDS-UPDRS Parts 2 or 3 tremor severity (not constancy) items;
10. Montreal cognitive assessment score < 25
11. History of any surgery on the brain itself including deep brain stimulation for PD (note this does not include surgeries on the skull that do not affect the brain, e.g., small meningioma removal);
12. History of hypersensitivity (e.g., bronchospasm, anaphylaxis, serious drug rash) to contents of the study drug or other tyrosine kinase inhibitors;
13. Recent use of medications that can cause Parkinsonism and suspicion of the investigator that it could have worsened the subject's Parkinsonism. This includes neuroleptics (e.g., olanzapine, risperidone, haloperidol), some anti-nausea medications (e.g., prochlorperazine, metoclopramide) and others (e.g., flunarizine, methyldopa)
14. Use of medications that affect the dopaminergic system within 60 days of Screening. This includes stimulants (e.g., methylphenidate, amphetamine derivatives, modafinil) and Monoamine Oxidase A (MAOA) inhibitors (e.g., phenelzine, and tranylcypromine). Note that antidepressants are acceptable as long as the subject has remained on them at a stable dose for over 60 days prior to Screening and plans to remain on them through the study;
15. Any malignant disease (other than basal cell carcinoma of the skin) with evidence of disease within the past 5 years and with the potential for recurrence

Part 2:

Inclusion criteria:

1. Subject has completed part 1 of the study.
2. Subject projected not to need dopaminergic treatment except for treatment with Monoamine Oxidase B (MAOB) inhibitors. MAOB inhibitors will be allowed if the patient was already taking the same during part 1 of the study.
3. Subject has received K0706/placebo, as appropriate, within 4 weeks prior to end of part 1 of the study.
4. Male subjects enrolled in the study should not father a child and are advised to prevent the passage of semen to their sexual partner during intercourse using an effective method, as judged by the Investigator, for the duration of the study and for 3 months after the last dose of study drug

Exclusion criteria:

1. Clinically significant or unstable psychiatric or medical condition, vital sign, or laboratory abnormality that in the opinion of the investigator interferes with participation in the study
2. Any condition that in the opinion of the Investigator represents an obstacle for study conduct and/or represents a potential unacceptable risk for the subject.
3. Subject has any concurrent medical condition or uncontrolled, clinically significant systemic disease (e.g., renal failure, heart failure, hypertension, liver disease, diabetes, or anemia) that, in the opinion of the Investigator, could cause continued treatment to be detrimental to the subject

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: placebo; placebo, orally, once-daily
Experimental: K0706, low dose	Drug: K0706; low dose, orally, once-daily; Drug: K0706; high dose, orally, once-daily
Experimental: K0706, high dose	Drug: K0706; low dose, orally, once-daily; Drug: K0706; high dose, orally, once-daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 40 in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Total Score.	Part III: Motor examination: 18 items. Score range: 0-132, 32 and below is mild, 59 and above is severe.	Week 40
Number of Participants With Treatment-emergent Adverse Events		Part 2 (Week 40 to 80)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Change From Baseline to Week 40 in the Sum of the MDS-UPDRS Part II and Part III Total Scores and Part 2: Change From Week 40 to Week 76 in the MDS-UPDRS Part III Total Score.	The Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II assesses the motor aspects of experiences of daily living based on patient self-report. It comprises 13 items, each rated on a 5-point scale ranging from 0 (normal) to 4 (severe impairment). The total score for Part II ranges from 0 to 52, calculated as the sum of the individual item scores. The MDS-UPDRS Part III assesses the motor symptoms of Parkinson's disease. This part consists of 18 items, which are assessed across various body regions, resulting in 33 individual scores. Each item is rated on a 5-point scale from 0 (normal) to 4 (severe impairment), with higher scores indicating greater motor dysfunction. The total score for Part III ranges from 0 to 132, which is the sum of the individual item scores. The sum of the MDS-UPDRS Part II and Part III total scores ranges from 0 to 184, with high scores indicating greater clinical impairment.	Part 1: Week 40 and Part 2: Week 76
To Determine if K0706 Delays the Initiation of Symptomatic Medications in Participants		Part 1: Week 40 and Part 2: Week 80 (Part 2 is applicable to the subjects who complete the EoT visit of part 1 (V11/Week 40) and who confirm their willingness to participate in part 2 of the study.
Change in Health Related Quality of Life as Measured by the European Quality of Life Questionnaire 5 Level Version	Health-Related quality of life (HRQoL) will be measured using the European Quality of Life Questionnaire 5 level version (EQ-5D-5L). This scale is numbered from 0 to 100. 100 means the best health you can imagine. 0 means the worst health you can imagine.	Week 40
Change in Clinician Global Impression Severity	The Clinician Global Impression Severity (CGIS) is a tool used to measure overall disease severity, assessed as follows: Normal; Borderline; Mild; Moderate; Marked; Severe; Among the Most Extremely Ill Patient	Week 40
Change in the Scales for Outcomes in Parkinson's Disease - Autonomic Questionnaire	The Scales for Outcome in Parkinson's disease - Autonomic (SCOPA-AUT) sum score is a sum of rating scores over 23 items. The SCOPA-AUT sum score ranges from 0 to 69. A higher score means a more severe autonomic dysfunction (i.e., a worse outcome). For each of the 23 items, the score ranges from 0 to 3. The rating scale is the follows: 0= Never experiencing the symptom; Sometimes experiencing the symptom;; Regularly experiencing the symptom;; Often experiencing the symptom	Week 40
Serum Concentration Level of K0706	Plasma pharmacokinetic (PK) samples were collected Week 28, per the Schedule of Assessment of the study protocol. There was no PK samples collected after Week 28 per the study protocol.	Week 28

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Outcome: Effect of K0706 on Dopamine Cell Health in Parkinson's Disease as Detected Via Dopamine Transporter Single Photon Emission Computed Tomography (DaT SPECT) Brain Imaging	Not available: The results of the exploratory analyses, including examination of CSF using the α-synuclein aggregation assay and measurement of neurofilament light, were not intended for interpretation of efficacy.	Week 40
CSF K0706 Levels Progression or Target Engagement of K0706.	Not available: The results of the exploratory analyses, including examination of CSF using the α-synuclein aggregation assay and measurement of neurofilament light, were not intended for interpretation of efficacy.	Week 40
Brain DaT SPECT - an Imaging Tool That is a Marker of Dopaminergic Cell Health.	Not available: The results of the exploratory analyses, including examination of CSF using the α-synuclein aggregation assay and measurement of neurofilament light, were not intended for interpretation of efficacy.	Week 40
Blood K0706 Levels	Not available: The results of the exploratory analyses, including examination of CSF using the α-synuclein aggregation assay and measurement of neurofilament light, were not intended for interpretation of efficacy.	Week 40
Skin Punch Biopsy	Not available: The results of the exploratory analyses, including examination of CSF using the α-synuclein aggregation assay and measurement of neurofilament light, were not intended for interpretation of efficacy.	Week 40

Collaborators and Investigators

• Sponsor: Sun Pharma Advanced Research Company Limited

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2019
• Primary Completion (Actual): April 8, 2024
• Study Completion (Actual): June 6, 2024

Study Registration Dates

• First Submitted: August 18, 2018
• First Submitted That Met QC Criteria: August 29, 2018
• First Posted (Actual): August 31, 2018

Study Record Updates

• Last Update Posted (Actual): July 25, 2025
• Last Update Submitted That Met QC Criteria: July 24, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• 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: CLR_18_06

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