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

• Sponsor: Sun Pharma Advanced Research Company Limited (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT03655236
• Collaborator: (none)
• Enrollment: 504
• Locations: 85
• Arms: 3
• Anticipated Duration (Months): 48.4
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Early Parkinson Disease	Drug: K0706; Drug: K0706; Other: placebo	Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 504 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of K0706 in Subjects With Early Parkinson's Disease
• Actual Study Start Date: Feb 18, 2019
• Anticipated Primary Completion Date: Mar 1, 2023
• Anticipated Study Completion Date: Mar 1, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change from Baseline in the sum of MDS-UPDRS Parts 2 and 3 [Week 40]

Secondary Outcome Measures

1. Change in the movement disorder society - unified Parkinson's disease rating scale [Week 40]

2. Time from Baseline to initiation of symptomatic medication [Week 40]

3. Change in health related quality of life as measured by the European quality of life questionnaire 5 level version [Week 40]

4. Change in Clinician global impression severity [Week 40]

5. Change in the scales for outcomes in Parkinson's disease - autonomic questionnaire [Week 40]

6. Level of K0706 [Week 40]

Other Outcome Measures

1. 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]

2. CSF K0706 levels progression or target engagement of K0706. [Week 40]

3. Brain DaT SPECT - an imaging tool that is a marker of dopaminergic cell health. [Week 40]

4. Blood K0706 levels [Week 40]

5. Skin punch biopsy [Week 40]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Xenoscience Inc. - 21st Century Neurology	Phoenix	Arizona	United States	85004
2	University of Arkansas for Medical Sciences (UAMS) - Movement Disorders Clinic	Little Rock	Arkansas	United States	72205
3	Keck Hospital of USC	Los Angeles	California	United States	90033
4	Georgetown University Medical Center Department of Neurology, 7PHC	Washington	District of Columbia	United States	20007
5	JEM Research Institute	Atlantis	Florida	United States	33462
6	Visionary Investigators Network	Aventura	Florida	United States	33180
7	Parkinson's Disease and Movement Disorders Center of Boca Raton, Inc.	Boca Raton	Florida	United States	33486
8	Neurology Associates PA	Maitland	Florida	United States	32751
9	Visionary Investigators Network	Miami	Florida	United States	33176
10	Medsol Clinical Research Center	Port Charlotte	Florida	United States	33952
11	Suncoast Neuroscience Associates, Inc.	Saint Petersburg	Florida	United States	33713
12	Emory University	Atlanta	Georgia	United States	30329
13	Rush University Medical Center	Chicago	Illinois	United States	60612
14	University of Kansas Medical Center (KUMC)	Kansas City	Kansas	United States	66160
15	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan	United States	48322
16	Struthers Parkinson's Center -Park Nicollet	Golden Valley	Minnesota	United States	55427
17	Washington University (WUSTL) School of Medicine	Saint Louis	Missouri	United States	63110
18	Renown Regional Medical Center	Reno	Nevada	United States	89502
19	Dartmouth-Hitchcock Medical Center (DHMC) Neurology Research	Lebanon	New Hampshire	United States	03756
20	Robert Wood Johnson Medical School Department of Neurology, Clinical Academic Building (CAB)	New Brunswick	New Jersey	United States	08901
21	Neurology Specialists of Monmouth County, PA	West Long Branch	New Jersey	United States	07764
22	Weill Cornell Medicine Department of Neurology Parkinson's Disease and Movement Disorders Institute	New York	New York	United States	10021
23	PMG Research of Winston-Salem	Winston-Salem	North Carolina	United States	27103
24	Cleveland Clinic	Cleveland	Ohio	United States	44195
25	The Movement Disorder Clinic of Oklahoma	Tulsa	Oklahoma	United States	74136
26	Oregon Health and Science University	Portland	Oregon	United States	97239
27	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
28	Baylor College of Medicine (BCM)- Parkinson's Disease Center and Movement Disorders Clinic (PDCMDC)	Houston	Texas	United States	77030
29	Houston Methodist Neurological Institute	Houston	Texas	United States	77030
30	Central Texas Neurology Consultants (CTNC)	Round Rock	Texas	United States	78681
31	Evergreen Health	Kirkland	Washington	United States	98034
32	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
33	Pecsi Tudomanyegyetem Általános Orvostudományi Kar	Pécs	Baranya	Hungary	7623
34	Nyiro Gyula Hospital	Budapest	Buapest	Hungary	1135
35	Szegedi Tudományegyetem; I.Belgyógyászati Klinika	Szeged	Csongrad	Hungary	6725
36	Petz Aladár Megyei Oktató Kórház	Győr	Gyor-Sopron	Hungary	9023
37	Clinexpert Gyogycentrum	Budapest	Komarom-Esztergom	Hungary	1031
38	Szent Borbála Kórház	Tatabánya	Komarom-Esztergom	Hungary	4032
39	Valeomed Diagnosztikai Kozpont	Esztergom	Komárom-Esztergom	Hungary	2500
40	Pest Megyei Flór Ferenc Kórház	Kistarcsa	Pest	Hungary	2143
41	Magyar Honvédség Egészségügyi Központ	Budapest		Hungary	1134
42	Semmelweis Egyetem- Altalanos Orvostudomanyi Kar- Pulmonologiai Klinika	Budapest		Hungary	1145
43	Medanta - The Medicity	Gurgaon	Haryana	India	122001
44	Nizam's Institute of Medical Sciences	Panjagutta	Hyderabad	India	500082
45	Parkinson's & Ageing Research Foundation	Bangalore	Karnataka	India	560092
46	Parkinson's & Ageing Research Foundation	Bengaluru	Karnataka	India	560095
47	Jaslok Hospital and Research centre	Mumbai	Maharashtra	India	400026
48	P.D. Hinduja National Hospital and Medical Care Research Centre	Mumbai	Maharastra	India	400016
49	Fortis Flt. Lt. Rajan Dhall Hospital	Vasant Kunj	New Delhi	India	110070
50	Medipoint Hospital	Aundh	Pune	India	411007
51	Lifepoint Multispeciality Hospital Pvt Ltd	Wakad	Pune	India	411057
52	Dayanand Medical College & Hospital, Research & Development Centre	Ludhiāna	Punjab	India	141001
53	Citi Neuro Centre	Hyderabad	Telangana	India	500 034
54	Institute of Neurosciences Kolkata	Kolkata	West Bengal	India	700017
55	Sir Ganga Ram Hospital	New Delhi		India	110060
56	Nasz Lekarz Osrodek Badan Klinicznych - Bydgoszcz	Bydgoszcz	Kujawsko-Pomorskie	Poland	85-065
57	Nasz Lekarz Przychodnie Medyczne Ośrodek Badań Klinicznych	Toruń	Kujawsko-Pomorskie	Poland	87-100
58	Lodzkie Centrum Osteoporozy SOMED	Lodz	Lodzkie	Poland	90-368
59	NZOZ Neuromed M. i M. Nastaj Sp. P.	Lublin	Lubelskie	Poland	20-097
60	ETG Lublin	Lublin	Lubelskie	Poland	20-412
61	Krakowska Akademia Neurologii	Krakow	Malopolskie	Poland	31-505
62	RCMed Oddział w Sochaczewie	Sochaczew	Mazowieckie	Poland	96-500
63	SINGUA Sp. Z o.o.	Warszawa	Mazowieckie	Poland	00-732
64	Altermed	Katowice	Slaskie	Poland	40-026
65	Neuro-Care - Sp. z o.o. Sp. Komandytowa Ul. Szpitalna 6	Siemianowice Śląskie	Slaskie	Poland	41-100
66	NZOZ Centrum Medyczne HCP	Poznań	Wielkopolskie	Poland	61-485
67	Mazowiecki Szpital Brodnowski w Warszawie Sp. z o.o.	Warszawa		Poland
68	NEURES, s.r.o.	Krompachy	Spiska Nova Ves	Slovakia	5342
69	Medical Center Konzilium	Dubnica Nad Váhom	Trencin	Slovakia	018 41
70	MUDr. Beata Dupejova, neurologicka ambulancia s.r.o	Banska Bystrica		Slovakia	974 04
71	University Hospital Bratislava	Bratislava		Slovakia	83101
72	Plaza de Cruces, S/N	Barakaldo	Bilbao	Spain	48903
73	Policlínica Gipuzkoa	San Sebastian	San Sebastián	Spain	20014
74	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08025
75	Hospital Universitario Vall d'Hebron	Barcelona		Spain	08035
76	Hospital Universitari General de Catalunya	Barcelona		Spain	08195
77	Hospital Universitari de Bellvitge (IDIBELL)	Barcelona		Spain	08907
78	Hospital Universitari de Girona Doctor Josep Trueta	Girona		Spain	17190
79	Hospital Universitario Virgen de las Nieves	Granada		Spain	18014
80	Hospital Universitario de la Princesa	Madrid		Spain	28006
81	Hospital Quiron Salud	Madrid		Spain	28040
82	Hospital Universitario Ramón y Caja	Madrid		Spain	28049
83	Clínica Universidad de Navarra	Pamplona		Spain	31008
84	Hospital Universitario Virgen del Rocío	Sevilla		Spain	41013
85	Hospital Universitario Dr. Peset	Valencia		Spain	46017

Sponsors and Collaborators

• Sun Pharma Advanced Research Company Limited

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sun Pharma Advanced Research Company Limited
• ClinicalTrials.gov Identifier: NCT03655236
• Other Study ID Numbers: CLR_18_06
• First Posted: Aug 31, 2018
• Last Update Posted: Aug 12, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Parkinson Disease

Study Results

No Results Posted as of Aug 12, 2022