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

Early Parkinson Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03655236
• Other study ID #: CLR_18_06
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 18, 2019
• Est. completion date: March 2024

Study information

• Verified date: November 2023
• Source: Sun Pharma Advanced Research Company Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 506
• Est. completion date: March 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Early Parkinson Disease
• Parkinson Disease

Intervention

Drug:
• K0706
low dose, orally, once-daily
• K0706
high dose, orally, once-daily

Other:
• placebo
placebo, orally, once-daily

Locations

Country	Name	City	State
Hungary	Nyiro Gyula Hospital	Budapest	Buapest
Hungary	Valeomed Diagnosztikai Kozpont	Esztergom	Komárom-Esztergom
Hungary	Pest Megyei Flór Ferenc Kórház	Kistarcsa	Pest
Hungary	Szent Borbála Kórház	Tatabánya	Komarom-Esztergom
India	Medipoint Hospital	Aundh	Pune
India	Citi Neuro Centre	Hyderabad	Telangana
India	Bangur Institute of Neurosciences & Psychiatry (BINP)	Kolkata
India	Institute of Neurosciences Kolkata	Kolkata	West Bengal
India	Dayanand Medical College & Hospital, Research & Development Centre	Ludhiana	Punjab
India	Jaslok Hospital and Research centre	Mumbai	Maharashtra
India	P.D. Hinduja National Hospital and Medical Care Research Centre	Mumbai	Maharastra
India	Sir Ganga Ram Hospital	New Delhi
India	Nizam's Institute of Medical Sciences	Panjagutta	Hyderabad
India	Deenanath Mangeshkar Hospital & Research Center (DMHRC)	Pune
India	Fortis Flt. Lt. Rajan Dhall Hospital	Vasant Kunj	New Delhi
India	Lifepoint Multispeciality Hospital Pvt Ltd	Wakad	Pune
Poland	C.M. Silmedic Sp. z o.o.	Katowice	Slaskie
Poland	Krakowska Akademia Neurologii	Krakow	Malopolskie
Poland	SOMED CR	Lódz	Lodzkie
Poland	ETG Lublin	Lublin	Lubelskie
Poland	NZOZ Neuromed M. i M. Nastaj Sp. P.	Lublin	Lubelskie
Poland	NZOZ Centrum Medyczne HCP	Poznan	Wielkopolskie
Poland	Neuro-Care - Sp. z o.o. Sp. Komandytowa Ul. Szpitalna 6	Siemianowice Slaskie	Slaskie
Poland	RCMed Oddzial w Sochaczewie	Sochaczew	Mazowieckie
Poland	Nasz Lekarz Przychodnie Medyczne Osrodek Badan Klinicznych	Torun	Kujawsko-Pomorskie
Poland	Mazowiecki Szpital Brodnowski w Warszawie Sp. z o.o.	Warszawa
Poland	SINGUA Sp. Z o.o.	Warszawa	Mazowieckie
Slovakia	MUDr. Beata Dupejova, neurologicka ambulancia s.r.o	Banska Bystrica
Slovakia	Medical Center Konzilium	Dubnica Nad Váhom	Trencin
Slovakia	NEURES, s.r.o.	Krompachy	Spiska Nova Ves
Spain	Plaza de Cruces, S/N	Barakaldo	Bilbao
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari de Bellvitge (IDIBELL)	Barcelona
Spain	Hospital Universitari General de Catalunya	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitari de Girona Doctor Josep Trueta	Girona
Spain	Hospital Universitario Virgen de las Nieves	Granada
Spain	Hospital Quiron Salud	Madrid
Spain	Hospital Universitario de la Princesa	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Clínica Universidad de Navarra	Pamplona
Spain	Policlínica Gipuzkoa	San Sebastian	San Sebastián
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Universitario Dr. Peset	Valencia
United States	Dent Neurologic Institute - Amherst	Amherst	New York
United States	Emory University	Atlanta	Georgia
United States	JEM Research Institute	Atlantis	Florida
United States	Visionary Investigators Network	Aventura	Florida
United States	Parkinson's Disease and Movement Disorders Center of Boca Raton, Inc.	Boca Raton	Florida
United States	Rush University Medical Center	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Advanced Neurology Epilepsy and Sleep Center	El Paso	Texas
United States	Struthers Parkinson's Center -Park Nicollet	Golden Valley	Minnesota
United States	Baylor College of Medicine (BCM)- Parkinson's Disease Center and Movement Disorders Clinic (PDCMDC)	Houston	Texas
United States	Houston Methodist Neurological Institute	Houston	Texas
United States	University of Kansas Medical Center (KUMC)	Kansas City	Kansas
United States	Evergreen Health	Kirkland	Washington
United States	Dartmouth-Hitchcock Medical Center (DHMC) Neurology Research	Lebanon	New Hampshire
United States	University of Arkansas for Medical Sciences (UAMS) - Movement Disorders Clinic	Little Rock	Arkansas
United States	Keck Hospital of USC	Los Angeles	California
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Neurology Associates PA	Maitland	Florida
United States	Visionary Investigators Network	Miami	Florida
United States	Robert Wood Johnson Medical School Department of Neurology, Clinical Academic Building (CAB)	New Brunswick	New Jersey
United States	Weill Cornell Medicine Department of Neurology Parkinson's Disease and Movement Disorders Institute	New York	New York
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Xenoscience Inc. - 21st Century Neurology	Phoenix	Arizona
United States	Medsol Clinical Research Center	Port Charlotte	Florida
United States	Oregon Health and Science University	Portland	Oregon
United States	Renown Regional Medical Center	Reno	Nevada
United States	Central Texas Neurology Consultants (CTNC)	Round Rock	Texas
United States	Washington University (WUSTL) School of Medicine	Saint Louis	Missouri
United States	Pacific Movement Disorders Center Pacific Neuroscience Institute Providence Saint John's Health Center	Santa Monica	California
United States	The Movement Disorder Clinic of Oklahoma	Tulsa	Oklahoma
United States	Georgetown University Medical Center Department of Neurology, 7PHC	Washington	District of Columbia
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	Neurology Specialists of Monmouth County, PA	West Long Branch	New Jersey
United States	PMG Research of Winston-Salem	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sun Pharma Advanced Research Company Limited

Countries where clinical trial is conducted

United States,  Hungary,  India,  Poland,  Slovakia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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		Week 40
Other	CSF K0706 levels progression or target engagement of K0706.		Week 40
Other	Brain DaT SPECT - an imaging tool that is a marker of dopaminergic cell health.		Week 40
Other	Blood K0706 levels		Week 40
Other	Skin punch biopsy		Week 40
Primary	Change from Baseline in the sum of MDS-UPDRS Parts 2 and 3		Week 40
Secondary	Change in the movement disorder society - unified Parkinson's disease rating scale		Week 40
Secondary	Time from Baseline to initiation of symptomatic medication		Week 40
Secondary	Change in health related quality of life as measured by the European quality of life questionnaire 5 level version		Week 40
Secondary	Change in Clinician global impression severity		Week 40
Secondary	Change in the scales for outcomes in Parkinson's disease - autonomic questionnaire		Week 40
Secondary	Level of K0706		Week 40