Clinical trial NCT03655236: PROSEEK: A Phase 2 Study In Early Parkinson's Disease Patients Evaluating The Safety And Efficacy Of Abl Tyrosine Kinase Inhibition Using K0706
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of K0706 in Subjects With Early Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Early Parkinson Disease
Lead sponsor: Sun Pharma Advanced Research Company Limited
Sponsor class: INDUSTRY
First posted: 2018-08-31
Enrollment: 513
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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., prochlorperizine, 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

Primary outcomes:
measure: Change from baseline to Week 40 in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III total score.
timeFrame: Week 40
measure: Incidence of treatment-emergent adverse events
timeFrame: Week 80
Secondary outcomes:
measure: Part 1: Change from baseline to Week 40 in the sum of the MDS-UPDRS Parts II and III total scores Part 2: Change from Week 40 to Week 76 in the sum of the MDS-UPDRS Part III scores
timeFrame: Part 1: Week 40 and Part 2: Week 76
measure: Time from first dose in Part 1 to initiation of symptomatic PD medications
timeFrame: Part 1: Week 40 and Part 2: Week 80
measure: Change in health related quality of life as measured by the European quality of life questionnaire 5 level version
timeFrame: Week 40
measure: Change in Clinician global impression severity
timeFrame: Week 40
measure: Change in the scales for outcomes in Parkinson's disease - autonomic questionnaire
timeFrame: Week 40
measure: Level of K0706
timeFrame: Week 40
Other outcomes:
measure: 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
timeFrame: Week 40
measure: CSF K0706 levels progression or target engagement of K0706.
timeFrame: Week 40
measure: Brain DaT SPECT - an imaging tool that is a marker of dopaminergic cell health.
timeFrame: Week 40
measure: Blood K0706 levels
timeFrame: Week 40
measure: Skin punch biopsy
timeFrame: Week 40
Locations:
city: Phoenix
country: United States
facility: Xenoscience Inc. - 21st Century Neurology
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences (UAMS) - Movement Disorders Clinic
state: Arkansas
city: Los Angeles
country: United States
facility: Keck Hospital of USC
state: California
city: Santa Monica
country: United States
facility: Pacific Movement Disorders Center Pacific Neuroscience Institute Providence Saint John's Health Center
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center Department of Neurology, 7PHC
state: District of Columbia
city: Atlantis
country: United States
facility: JEM Research Institute
state: Florida
city: Aventura
country: United States
facility: Visionary Investigators Network
state: Florida
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Boca Raton, Inc.
state: Florida
city: Maitland
country: United States
facility: Neurology Associates PA
state: Florida
city: Miami
country: United States
facility: Visionary Investigators Network
state: Florida
city: Port Charlotte
country: United States
facility: Medsol Clinical Research Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center (KUMC)
state: Kansas
city: West Bloomfield
country: United States
facility: Henry Ford West Bloomfield Hospital
state: Michigan
city: Golden Valley
country: United States
facility: Struthers Parkinson's Center -Park Nicollet
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University (WUSTL) School of Medicine
state: Missouri
city: Reno
country: United States
facility: Renown Regional Medical Center
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center (DHMC) Neurology Research
state: New Hampshire
city: New Brunswick
country: United States
facility: Robert Wood Johnson Medical School Department of Neurology, Clinical Academic Building (CAB)
state: New Jersey
city: West Long Branch
country: United States
facility: Neurology Specialists of Monmouth County, PA
state: New Jersey
city: Amherst
country: United States
facility: Dent Neurologic Institute - Amherst
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine Department of Neurology Parkinson's Disease and Movement Disorders Institute
state: New York
city: Winston-Salem
country: United States
facility: PMG Research of Winston-Salem
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Tulsa
country: United States
facility: The Movement Disorder Clinic of Oklahoma
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: El Paso
country: United States
facility: Advanced Neurology Epilepsy and Sleep Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine (BCM)- Parkinson's Disease Center and Movement Disorders Clinic (PDCMDC)
state: Texas
city: Houston
country: United States
facility: Houston Methodist Neurological Institute
state: Texas
city: Round Rock
country: United States
facility: Central Texas Neurology Consultants (CTNC)
state: Texas
city: Kirkland
country: United States
facility: Evergreen Health
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Budapest
country: Hungary
facility: Nyiro Gyula Hospital
state: Buapest
city: Tatabánya
country: Hungary
facility: Szent Borbála Kórház
state: Komarom-Esztergom
city: Esztergom
country: Hungary
facility: Valeomed Diagnosztikai Kozpont
state: Komárom-Esztergom
city: Kistarcsa
country: Hungary
facility: Pest Megyei Flór Ferenc Kórház
state: Pest
city: Panjagutta
country: India
facility: Nizam's Institute of Medical Sciences
state: Hyderabad
city: Mumbai
country: India
facility: Jaslok Hospital and Research centre
state: Maharashtra
city: Mumbai
country: India
facility: P.D. Hinduja National Hospital and Medical Care Research Centre
state: Maharastra
city: Vasant Kunj
country: India
facility: Fortis Flt. Lt. Rajan Dhall Hospital
state: New Delhi
city: Aundh
country: India
facility: Medipoint Hospital
state: Pune
city: Wakad
country: India
facility: Lifepoint Multispeciality Hospital Pvt Ltd
state: Pune
city: Ludhiāna
country: India
facility: Dayanand Medical College & Hospital, Research & Development Centre
state: Punjab
city: Hyderabad
country: India
facility: Citi Neuro Centre
state: Telangana
city: Kolkata
country: India
facility: Institute of Neurosciences Kolkata
state: West Bengal
city: Kolkata
country: India
facility: Bangur Institute of Neurosciences & Psychiatry (BINP)
city: New Delhi
country: India
facility: Sir Ganga Ram Hospital
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital & Research Center (DMHRC)
city: Toruń
country: Poland
facility: Nasz Lekarz Przychodnie Medyczne Ośrodek Badań Klinicznych
state: Kujawsko-Pomorskie
city: Łódź
country: Poland
facility: SOMED CR
state: Lodzkie
city: Lublin
country: Poland
facility: NZOZ Neuromed M. i M. Nastaj Sp. P.
state: Lubelskie
city: Lublin
country: Poland
facility: ETG Lublin
state: Lubelskie
city: Krakow
country: Poland
facility: Krakowska Akademia Neurologii
state: Malopolskie
city: Sochaczew
country: Poland
facility: RCMed Oddział w Sochaczewie
state: Mazowieckie
city: Warszawa
country: Poland
facility: SINGUA Sp. Z o.o.
state: Mazowieckie
city: Katowice
country: Poland
facility: C.M. Silmedic Sp. z o.o.
state: Slaskie
city: Siemianowice Śląskie
country: Poland
facility: Neuro-Care - Sp. z o.o. Sp. Komandytowa Ul. Szpitalna 6
state: Slaskie
city: Poznań
country: Poland
facility: NZOZ Centrum Medyczne HCP
state: Wielkopolskie
city: Warszawa
country: Poland
facility: Mazowiecki Szpital Brodnowski w Warszawie Sp. z o.o.
city: Krompachy
country: Slovakia
facility: NEURES, s.r.o.
state: Spiska Nova Ves
city: Dubnica Nad Váhom
country: Slovakia
facility: Medical Center Konzilium
state: Trencin
city: Banska Bystrica
country: Slovakia
facility: MUDr. Beata Dupejova, neurologicka ambulancia s.r.o
city: Barakaldo
country: Spain
facility: Plaza de Cruces, S/N
state: Bilbao
city: San Sebastian
country: Spain
facility: Policlínica Gipuzkoa
state: San Sebastián
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Universitari General de Catalunya
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge (IDIBELL)
city: Girona
country: Spain
facility: Hospital Universitari de Girona Doctor Josep Trueta
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
city: Madrid
country: Spain
facility: Hospital Quiron Salud
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset
Study officials:
References: