This study evaluates the safety and tolerability of treatment with K0706 in Dementia with Lewy Bodies (DLB).
The hypothesis is that K0706 will be safe and tolerable and that this drug will alter CSF and plasma biomarkers in DLB. Clinical assessments of cognitive, behavioral and motor functioning will also be evaluated. A total of 45 participants will be randomized 1:1:1 into 3 groups (n=15/per group) to be treated with oral daily doses of 96 mg K0706 (group 1), 192mg K0706 (group 2) or matching placebo (group 3) for 12 weeks, followed by 4-week wash-out period.
Condition or disease | Intervention/treatment | Phase |
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Dementia With Lewy Bodies | Drug: Placebo oral capsule Drug: 96 mg of K0706 Drug: 192 mg K0706 | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 45 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | The effects of 92mg of K0706 versus 196mg of K0706 versus matching placebo taken daily by mouth for 12 weeks, followed by a 4 week wash-out period in individuals diagnosed with DLB will be evaluated. |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Masking Description: | Participants will be randomized by a Biostatistician by an internet based randomization module into three groups. The researchers include : Primary investigator , Sub-Investigators ,Clinical Coordinators, Nurse Practitioners, and Clinical Research unit (CRU) staff. The investigators will be blinded to the dosage. Medications for any patient will be labeled by the CRU with a package medical identification number (Med. Id). A patient specific patient identification number (Pat. Id.) will be assigned to each patient. The investigator will have to note the Pat.Id on the designated medication package number after randomization. |
Primary Purpose: | Treatment |
Official Title: | A Randomized, Double Blind, Placebo-controlled Study to Evaluate the Impact of K0706 on Safety, Tolerability, Pharmacokinetics and Pharmacodynamics and Clinical Outcomes in Dementia With Lewy Bodies (DLB) |
Actual Study Start Date : | September 5, 2019 |
Estimated Primary Completion Date : | January 2021 |
Estimated Study Completion Date : | August 2021 |
Arm | Intervention/treatment |
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Placebo Comparator: Placebo
Forty five (45) participants will be recruited and randomized into 3 arms (1:1:1). Fifteen (15) patients in arm 1 (group 1) will receive the matching placebo (8 x Placebo capsules) ("sugar pill") orally once daily for 12 weeks (90 days).
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Drug: Placebo oral capsule
Fifteen (15) patients in group 1 will receive the matching placebo ("sugar pill") eight (8) capsule orally daily for 12 weeks (90 days) without food.
Other Name: Placebo
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Active Comparator: 96 mg of K0706
Forty five (45) participants will be recruited and randomized into 3 arms (1:1:1) .Fifteen (15) patients in arm 2 (group 2) will receive the 96 mg of K0706 (4 x 24 mg K0706 and 4 Placebo capsules) orally once daily for 12 weeks (90 days).
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Drug: 96 mg of K0706
Fifteen (15) patients in group 2 will receive the 96 mg of K0706 (4 x 24 mg of K0706) orally and four placebo capsules daily for 12 weeks (90 days) without food.
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Active Comparator: 192 mg of K0706
Forty five (45) participants will be recruited and randomized into 3 arms (1:1:1) .Fifteen (15) patients in arm 3 (group 3) will receive 192 mg of K0706 (8 x 24 mg K0706 capsules) orally once daily for 12 weeks(90 days).
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Drug: 192 mg K0706
Fifteen (15) patients in group 3 will receive the 192 mg of K0706 (8 x 24 mg of K0706) orally daily for 12 weeks (90 days) without food.
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Ages Eligible for Study: | 25 Years to 90 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Myrna Joy J Arellano, RN | (202)-444-7273 | mja6@gunet.georgetown.edu | |
Contact: Sara Matar, BS | 202-687-7581 | sm3469@georgetown.edu |
United States, District of Columbia | |
MedStar Georgetown University Hospital | Recruiting |
Washington, District of Columbia, United States, 20007 | |
Contact: Fernando L Pagan, MD 202-444-8525 fpogan01@gunet.georgetown.edu | |
Contact: Sara Matar, BS 202-687-7581 sm3469@georgetown.edu | |
Principal Investigator: Fernando L Pagan, MD | |
Sub-Investigator: Charbel E Moussa, MD,PhD |
Principal Investigator: | Fernando L Pagan, MD | Georgetown University |
Tracking Information | |||||||||
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First Submitted Date ICMJE | June 13, 2019 | ||||||||
First Posted Date ICMJE | June 24, 2019 | ||||||||
Last Update Posted Date | September 24, 2020 | ||||||||
Actual Study Start Date ICMJE | September 5, 2019 | ||||||||
Estimated Primary Completion Date | January 2021 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
Evidence of treatment-emergent adverse effects (safety and tolerability) [ Time Frame: 12 weeks ] The investigators will determine safety and tolerability by using the occurrence of adverse events (AEs) of interest, including myelosuppression, urinary, pancreatic and hepatic disorders, gastrointestinal (GI), kidney disorders, Corrected QT-interval (QTc)prolongation as per SPARC Ltd Investigator Brochure (IB).
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Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
Current Other Pre-specified Outcome Measures |
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Original Other Pre-specified Outcome Measures | Same as current | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | K0706 for Patients Diagnosed With Dementia With Lewy Bodies | ||||||||
Official Title ICMJE | A Randomized, Double Blind, Placebo-controlled Study to Evaluate the Impact of K0706 on Safety, Tolerability, Pharmacokinetics and Pharmacodynamics and Clinical Outcomes in Dementia With Lewy Bodies (DLB) | ||||||||
Brief Summary |
This study evaluates the safety and tolerability of treatment with K0706 in Dementia with Lewy Bodies (DLB). The hypothesis is that K0706 will be safe and tolerable and that this drug will alter CSF and plasma biomarkers in DLB. Clinical assessments of cognitive, behavioral and motor functioning will also be evaluated. A total of 45 participants will be randomized 1:1:1 into 3 groups (n=15/per group) to be treated with oral daily doses of 96 mg K0706 (group 1), 192mg K0706 (group 2) or matching placebo (group 3) for 12 weeks, followed by 4-week wash-out period. |
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Detailed Description | Dementia with Lewy Bodies (DLB) is an alpha-synucleinopathy and the second most common form of dementia in the elderly. DLB shares striking neuropathological and clinical similarities with both Parkinson's disease (PD) and Alzheimer's disease (AD). DLB and PD are characterized by death of dopaminergic (DA) neurons in the nigro-striatal system and formation of intra-neuronal alpha-synuclein inclusions known as Lewy bodies (LBs). Misfolded alpha-synuclein aggregates within LBs and apha-synuclein (SYN) is the highest genetic risk factor for PD and DLB followed by the microtubule associated protein tau (MAPT) . At autopsy alpha-synuclein, hyper-phosphorylated tau (p-tau) and amyloid plaques are all detected in the brains of individuals with DLB. Therefore, the neuropathology of DLB overlaps with both PD and AD, and includes alpha-synuclein accumulation in LBs, p-tau and beta-amyloid deposition . Potential cerebrospinal fluid (CSF) biomarkers, including alpha-synuclein, dopamine metabolites homovanillic acid (HVA) and 3,4-Dihydroxyphenylacetic acid (DOPAC) , total tau and p-tau and amyloid beta peptides (Abeta 40/42) may be commonly shared in AD, PD and DLB. The core clinical features of DLB, include dementia and Parkinsonism in addition to hallucinations, cognitive fluctuations and rapid eye movement (REM) sleep behavior disorders (RBD) . L-Dopa replacement therapies and acetylcholinesterase inhibitors may partially control motor and cognitive symptoms, respectively in DLB. Selective Serotonin Re-uptake Inhibitors (SSRIs) and antipsychotics manage the behavioral but worsen motor symptoms in DLB. There is a major unmet medical need for further research into DLB to identify potential therapies for this disease and provide significant insights into the treatment of other Parkinsonian and memory disorders. A major challenge facing DLB is to develop a therapy that can halt neuronal death and alleviate cognitive, motor and behavioral symptoms. No therapeutic approach exists to alter the levels of neurotoxic proteins such as alpha-synuclein and halt DA and other neuronal death in DLB. One mechanism to degrade neurotoxic proteins is autophagy , which is a process by which the cell can degrade its own contents. There is evidence that autophagy is impaired in neurodegeneration , leading to failure of degradation of protein aggregates, including misfolded alpha-synuclein. Importantly, autophagy is exploited therapeutically in several diseases, including adult chronic myeloid leukemia (CML). Tyrosine kinase inhibitors (TKIs) induce autophagy, leading to destruction of rapidly dividing tumor cells in CML and degradation of neurotoxic proteins, including alpha-synuclein, beta-amyloid and p-tau in PD and AD models. Sun Pharma Advanced Research Company Limited (SPARC Ltd.) is developing K0706, for the treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) that is resistant or intolerant to prior TKI therapy or Philadelphia positive acute lymphoblastic leukemia (Ph+ ALL) that is resistant or intolerant to prior TKI therapy; and its ability to slow down progression of PD. Using allometric scaling and an average human body weight of 70kg an oral dose of 15-30mg/kg once daily in mice corresponds to an oral human equivalent dose (HED) of 85-160 mg which is within the tolerated dose in both CML and PD. Therefore, the effects of 96 mg K0706 and 192 mg K0706 versus matching placebo taken daily by mouth for 12 weeks, followed by a 4 week wash-out period will be evaluated in individuals diagnosed with DLB. The data obtained from this study will serve as a proof of concept for future placebo-controlled, double-blind studies in patients diagnosed with DLB, AD, or PD. | ||||||||
Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 2 | ||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: The effects of 92mg of K0706 versus 196mg of K0706 versus matching placebo taken daily by mouth for 12 weeks, followed by a 4 week wash-out period in individuals diagnosed with DLB will be evaluated. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Masking Description: Participants will be randomized by a Biostatistician by an internet based randomization module into three groups. The researchers include : Primary investigator , Sub-Investigators ,Clinical Coordinators, Nurse Practitioners, and Clinical Research unit (CRU) staff. The investigators will be blinded to the dosage. Medications for any patient will be labeled by the CRU with a package medical identification number (Med. Id). A patient specific patient identification number (Pat. Id.) will be assigned to each patient. The investigator will have to note the Pat.Id on the designated medication package number after randomization. |
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Condition ICMJE | Dementia With Lewy Bodies | ||||||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
45 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | August 2021 | ||||||||
Estimated Primary Completion Date | January 2021 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 25 Years to 90 Years (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT03996460 | ||||||||
Other Study ID Numbers ICMJE | STUDY00000266 | ||||||||
Has Data Monitoring Committee | Yes | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Fernando Pagan MD, Georgetown University | ||||||||
Study Sponsor ICMJE | Georgetown University | ||||||||
Collaborators ICMJE | Sun Pharma Advanced Research Company Limited | ||||||||
Investigators ICMJE |
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PRS Account | Georgetown University | ||||||||
Verification Date | September 2020 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |