PROSEEK: A Phase 2 Study In Early Parkinsons Disease Patients Evaluating The Safety And Efficacy Of Abl Tyrosine Kinase Inhibition Using K0706.
Phase 2
Active, not recruiting
- Conditions
- Parkinsons disease,
- Registration Number
- CTRI/2019/10/021792
- Lead Sponsor
- Sun Pharma Advanced Research Company Limited
- Brief Summary
This study consists of 2 parts. Part 1 of thestudy is conducted to evaluate the efficacy, safety, and tolerability of twodoses of K0706 compared to placebo in subjects with early Parkinson’s Diseasewho are not receiving dopaminergic therapy. Part 2 is an optional long termextension study for subjects who have completed week 40 of Part 1. Patients canchoose to participate in Part 2 of the study. The extension study was designedto evaluate the safety and efficacy of the study drug at 76 weeks.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- All
- Target Recruitment
- 506
Inclusion Criteria
- The subject has given written informed consent and is willing to participate in the study; 2.
- Subject is able to understand and comply with all study procedures (requires literacy in available language of all patient-reported outcome measures); 3.
- Males or females aged ≥ 50 years; 4.
- Body mass index (BMI) greater than 18.5 kg/m2 and less than 45 kg/m2; 5.
- 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; 6.
- Projected to not require to start dopaminergic therapy within 9 months from Baseline; 7.
- Female subjects must be not of childbearing potential, e.g., documented evidence that they are surgically sterile (e.g., hysterectomy, partial hysterectomy, bilateral oophorectomy, bilateral tubal ligation), or post-menopausal (at least 12 months since last menses) prior to Screening.
- Male subjects enrolled in the study should not father a child and are advised to prevent 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; 9.
- Willingness to undergo lumbar puncture and skin biopsy for future testing of substances related to PD or K0706 target engagement.
- PART 2: Subject has completed the part 1 of the study.
- 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.
- Subject has received K0706/placebo, as appropriate, within 4 weeks prior to end of part 1 of the study.
Exclusion Criteria
- 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 (e.g., hypersensitivity to the active substance, any of the excipients, or iodine) if a new DaT SPECT 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 central reading by a study physician; 8.
- MRI scan 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.
- 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; 14.
- Any clinically significant cardiac abnormality in the opinion of the investigator.
- This would include myocardial infarction in the six months prior to screening, or significant ECG abnormality, including heart-rate corrected interval QT (QTc) based on Fridericia’s correction formula > 450 milliseconds for males and > 470 milliseconds for females; 15.
- History or presence of any gastrointestinal disorder or malabsorption syndrome, which might affect absorption of study drug; 16.
- History of surgery within 4 weeks prior to Screening visit or is expected to undergo a planned surgical procedure or invasive diagnostic procedure during the course of the study; 19.
- Participation in other investigational drug trials within 30 days prior to Screening; 20.
- This includes neuroleptics (e.g., olanzapine, risperidone, haloperidol), some anti-nausea medications (e.g., prochlorperizine, metoclopramide) and others (e.g., flunarizine, methyldopa); 22.
- Use of medications that affect the dopaminergic system though do not cause or treat PD, 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; 23.
- 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; 24.
- Female subjects presently lactating; Exclusion criteria specific for the Biomarker substudy: 25.
- Contraindications to undergoing a skin biopsy (e.g., allergy to the anesthetic used, use of anticoagulants or dual anti-platelet agents, history of impaired wound healing, history of keloid formation); 26.
- Contraindications for performing lumbar puncture such as coagulation disorders, back surgery that might interfere with the procedure, anticoagulants, etc.
- PART 2Exclusion 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.
- 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 & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Change from baseline to Week 40 in the Movement Disorder Society - Unified Parkinsons Disease Rating Scale (MDS-UPDRS) Part III total score. Part 1: Baseline to Week 40 | Part 2- Week 40 to Week 80 Incidence of treatment-emergent adverse events Part 1: Baseline to Week 40 | Part 2- Week 40 to Week 80
- Secondary Outcome Measures
Name Time Method Part 1: Evaluation of slopes of mean MDS-UPDRS part II & III scores over time during part 1 by treatment group Part 1 Change in MDS-UPDRS grand total score (sum of Parts I, II, & III) from the baseline Part 2: Change from Week 40 (Baseline for part 2) through week 76 in MDS-UPDRS Part IA, Part IB, Part I total, Part II total & Part III subscores. Time from the first dose in Part 1 to initiation of symptomatic PD medication. Part 1: Baseline to Week 40 Proportion of patients starting symptomatic treatment. Part 1: Baseline to Week 40 Time from Baseline to initiation of symptomatic medication Part 1: Baseline to Week 40 Change in HRQoL using the EQ-5D-5L from Baseline to Week 40 Part 1: Baseline to Week 40 Change in CGIS from Baseline to Week 40 Part 1: Baseline to Week 40 The Proportion of patients starting symptomatic PD treatment. Part 2 : Week 40 to Week 80 Change in the mean total MDS-UPDRS Parts I, II & III scores between the early-start & delayed-start groups at 76 weeks Part 2 : Week 40 to Week 76 Time from Week 40 (Baseline for Part 2) to initiation of symptomatic PD medication in the long term extension study Part 2: Week 40 to Week 80 Other Outcomes Measures - Part 1 CSF K0706 levels progression or target engagement of K0706 Change in the SCOPA-AUT from Baseline to Week 40 Part 1: Baseline to Week 40 Pharmacokinetics – Plasma & CSF levels of K0706 & any relevant metabolites Part 1: Baseline to Week 40
Trial Locations
- Locations (13)
Aster CMI Hospital
🇮🇳Bangalore, KARNATAKA, India
Bangur Institute of Neurosciences and Institute of Post Graduate Medical Education and Research
🇮🇳Kolkata, WEST BENGAL, India
Citi Neuro Centre
🇮🇳Hyderabad, TELANGANA, India
Dayanand Medical College & Hospital, Research & Development Centre,
🇮🇳Ludhiana, PUNJAB, India
Deenanath Mangeshkar Hospital & Research Center (DMHRC)
🇮🇳Pune, MAHARASHTRA, India
Fortis Flt. Lt .Rajan Dhall Hospital
🇮🇳Delhi, DELHI, India
Institute of Neurosciences Kolkata
🇮🇳Kolkata, WEST BENGAL, India
Jaslok Hospital and Research centre
🇮🇳Mumbai, MAHARASHTRA, India
Lifepoint Multispecialty Hospital
🇮🇳Pune, MAHARASHTRA, India
Medipoint Hospitals Pvt.Ltd.
🇮🇳Pune, MAHARASHTRA, India
Scroll for more (3 remaining)Aster CMI Hospital🇮🇳Bangalore, KARNATAKA, IndiaDr Sirnivasa RPrincipal investigator918022183125drrsrinivasa@hotmail.com