Safety and Efficacy of DA-9805 for Parkinson’s Disease
This is a phase IIa, first in human, randomized, double-blind, multicenter study to evaluate the safety, tolerability and efficacy of DA-9805 at 45mg, 90mg versus placebo in subjects diagnosed with early Parkinson’s disease.
Parkinson’s disease (PD) is recognized as one of the most common neurologic disorders, affecting approximately 1% of individuals older than 60 years. There are 2 major neuropathologic findings: the loss of pigmented dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of Lewy bodies.
Parkinson’s disease affects an estimated 1.5 million persons in the United States, with over ten million affected worldwide, and these estimates are expected to increase substantially in the next few decades. Despite the increasing prevalence, the approved agents for the early management of Parkinson’s disease have changed little in the past decade; however, there have been advances in drug delivery, dosing, and the use of combination therapy in an attempt to reduce adverse events. The most important, unmet medical need in targeting Parkinson’s disease is developing agents with neuroprotective potential. So far, no drug has been shown to reduce or slow down the progression of PD.
DA-9805 is a botanical drug product composed of three main raw herbal materials. It is expected that DA-9805 will help treat PD by prevention of dopaminergic neurodegeneration via recovery of mitochondrial dysfunction, anti-inflammatory effect and relief from Endoplasmic reticulum (ER) stress and oxidative stress.
Are You a Candidate?
- Male or female subjects who are between 30 and 79 years old inclusive with a clinical diagnosis of Parkinson’s disease as per UK Brain Bank Criteria for two (2) years or less at screening.
- Hoehn and Yahr I or II at screening
- Subjects who are newly diagnosed & currently not on any Parkinson’s disease medication (or) subjects who are on stable doses for at least 4 weeks prior to screening on Amantadine or anticholinergics for treatment of Parkinson’s disease
- Note: Subjects that had anti-parkinsonian medication (including levodopa, dopamine agonists, entacapone and monoamine oxidase-B inhibitors) discontinued at least 60 days prior to screening, e.g., for intolerance, may be considered eligible if all other eligibility requirements are met
- Women of child-bearing potential should use reliable contraception. Acceptable methods of contraception include: surgical sterilization (e.g. bilateral tubal ligation), hormonal contraception (implantable, patch, and oral), and double-barrier methods (condom, diaphragm and spermicide are each considered a barrier). Women of child-bearing potential are defined as women physiologically capable of becoming pregnant, UNLESS they meet the following criteria:
- Post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum Follicle Stimulating Hormone (FSH) levels > 40mIU/m, OR;
- 6 weeks post surgical bilateral oophorectomy with or without hysterectomy
- If a male and heterosexually active with a female of childbearing potential, the subject must agree to use a double barrier method of birth control (or must have been surgically sterilized) and to not donate sperm during the study
- Without clinically significant abnormalities in physical exam, neurological exam and laboratory assessments (urine/blood routine, biochemical tests and ECG) which would exclude the subject from the study in the opinion of the Investigator. For Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) the screening levels should be ≤ 2 times upper limit normal
- Subject is capable of providing informed consent and is willing to sign the ICF prior to study Screening and agrees to comply with the study protocol requirements
- Subject has an atypical parkinsonian syndrome or secondary parkinsonism (e.g., due to drugs, metabolic neurogenetic disorders, encephalitis, cerebrovascular disease or degenerative disease)
- Subjects with history of neurosurgical intervention for Parkinson’s disease
- Subjects who meet the DSM-V criteria at screening for bipolar disorder, major depressive disorder, psychotic disorders, or any other comorbid mental disorders that in the opinion of the Investigator may interfere with study conduct and results interpretation
- Subjects with clinical diagnosis of dementia (MMSE score <24) as determined by the investigator using Mini-Mental State Examination (MMSE)
- Female subjects who are pregnant or breast feeding
- Initiation of any anti-parkinsonian medication (including levodopa, dopamine agonists, entacapone and monoamine oxidase-B inhibitors) for the duration of the trial
- Initiation of Amantadine or anticholinergics for newly diagnosed subjects or change in the dosage of Amantadine or anticholinergics during the trial for subjects who were on stable doses for 4 weeks prior to screening
- Subjects who used investigational drugs or devices within 60 days prior to screening or investigational biologics within the last 6 months prior to screening
- Subjects with a clinically significant or surgical condition, including major surgeries within 28 days prior to enrollment
DSP-7888 Dosing Emulsion in Combination With Bevacizumab in Patients With Recurrent or Progressive Glioblastoma Following Initial Therapy (WIZARD 201G)
This is a randomized, active-controlled, multicenter, open-label, parallel groups, Phase 2 study of DSP-7888 Dosing Emulsion plus Bevacizumab versus Bevacizumab alone in patients with recurrent or progressive glioblastoma multiforme (GBM) following treatment with first line therapy consisting of surgery and radiation with or without chemotherapy.
Are You a Candidate?
- Patients or their legal representatives must be able to provide written informed consent
- Histologically confirmed diagnosis of supratentorial GBM (Grade 4 astrocytoma)
- Radiographic evidence of first recurrence or progression of GBM following primary therapy consisting of surgery (biopsy or resection) and chemoradiation; patients may have undergone a second debulking surgery following initial recurrence or progression. Patients whose tumors are O6 methyl guanyl-methyl-transferase (MGMT) methylated-promoter negative need not have received chemotherapy in the past to be eligible
- Human leukocyte antigen type HLA-A*02:01, HLA-A*02:06, or HLA-A*24:02
- Age ≥18
- KPS score of ≥60
- Serum creatinine value <2X the upper limit of normal (ULN) for the reference laboratory
- Alanine aminotransferase/aspartate aminotransferase <3X the ULN and total bilirubin <2× the ULN for the reference laboratory
- Patients must have recovered from the effect of all prior therapy to Grade 2 or less
- Patients must be at least 28 days from any major surgery, and any surgery incisions or wounds must be completely healed
- Patients must be at least 12 weeks from the completion of prior radiation therapy (RT) in order to discriminate pseudo progression of disease from progression
- Patients must be at least 4 weeks from the completion of prior systemic or intracranial chemotherapy
- For patients who are not receiving therapeutic anticoagulation treatment, an international normalized ratio (INR) and a PTT ≤ 1.5 × the ULN; patients who are receiving anticoagulation treatment should be on a stable dose
- Prior therapy with Bev
- Any anti-neoplastic therapy, including RT, for first relapse or recurrence
- Evidence of leptomeningeal spread of tumor or any history, presence, or suspicion of metastatic disease extracranially
- Evidence of impending herniation on imaging
- Patients with infections that have required treatment with systemic antibiotics within 7 days of first dose of protocol therapy
- The need for systemic glucocorticoids in doses in excess of 4 mg/day of dexamethasone or in comparable doses with other glucocorticoids
- Treatment with any investigational agents within 5 half-lives of the agent in question or, if the half life is unknown, within 28 days of enrollment
- Pregnant or lactating females
- Prior history of malignancy within 3 years of enrollment other than basal or squamous cell carcinoma of the skin, cervical intra-epithelial neoplasia, in situ carcinoma of the breast, or prostate cancer treated with surgery or RT with a prostate specific antigen of <0.01 ng/mL
- Patients with active autoimmune diseases within 2 years of enrollment into the study including, but not limited to, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren’s syndrome, Wegener’s granulomatosis, ulcerative colitis, Crohn’s disease, myasthenia gravis, Graves’ disease, or uveitis except for psoriasis not requiring systemic therapy, vitiligo or alopecia areata, or hypothyroidism; if an autoimmune condition has been clinically silent for 12 months or greater, the patient may be eligible for enrollment
- Patients on immunosuppressive therapies; the use of topical, inhalational, ophthalmologic or intra articular glucocorticoids, or the use of physiologic replacement doses of glucocorticoids are permitted
- Patients with primary immunodeficiency diseases
- Patients with significant bleeding in the preceding 6 months or with known coagulopathies
- History of abdominal fistula, intestinal perforation, or intra-abdominal abscess in the preceding 12 months
- Known history of human immunodeficiency virus (HIV) infection, active hepatitis B, or untreated hepatitis C; patients who have completed a course of anti-viral treatment for hepatitis C are eligible
- Significant cardiovascular disease, including New York Hospital Association Class III or IV congestive heart failure, myocardial infarction within 6 months of enrollment, unstable angina, poorly controlled cardiac arrhythmias, or stroke within the preceding 6 months
- Any other uncontrolled inter current medical condition, including systemic fungal, bacterial, or viral infection; uncontrolled hypertension; diabetes mellitus; or chronic obstructive pulmonary disease requiring 2 or more hospitalizations in the preceding 12 months
- Known sensitivity to Bev or any of the components of DSP-7888 Dosing Emulsion
Alzheimer’s Disease Neuroimaging Initiative 3 (ADNI3) Protocol
Since its launch in 2004, the overarching aim of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) has been realized in informing the design of therapeutic trials in AD. ADNI3 continues the previously funded ADNI-1, ADNI-GO, and ADNI-2 studies that have been combined public/private collaborations between academia and industry to determine the relationships between the clinical, cognitive, imaging, genetic and biochemical biomarker characteristics of the entire spectrum of Alzheimer’s disease (AD). The overall goal of the study is to continue to discover, optimize, standardize, and validate clinical trial measures and biomarkers used in AD research.
The overall goal of ADNI3 is to determine the relationships among the clinical, cognitive, imaging, genetic and biochemical biomarker characteristics of the entire spectrum of Alzheimer’s disease (AD), as the pathology evolves from normal aging through very mild symptoms, to mild cognitive impairment (MCI), to dementia. ADNI3 continues the previously funded AD Neuroimaging Initiative (ADNI1, ADNI-GO, and ADNI-2), and remains a public/private collaboration between academia and industry to study biomarkers of AD. ADNI will continue to inform the neuroscience of AD, identify diagnostic and prognostic markers, identify outcome measures that can be used in clinical trials, and help develop the most effective clinical trial scenarios.
This is multi-center, a non-randomized, natural history, non-treatment study. 1,070-2,000 total participants will be enrolled across three cohorts: cognitively normal* (CN), mild cognitive impairment (MCI) and mild Alzheimer’s Disease (AD) dementia. Participants between the ages of 55-90 (inclusive) will be enrolled at 59 sites in the United States and Canada. Approximately, 700 – 800 will be rollover participants from previous ADNI studies, and 370 – 1200 will be newly enrolled. Clinical/cognitive, imaging, biomarker, and genetic characteristics will be assessed across the three cohorts.
Participants will undergo longitudinal clinical and cognitive assessments, computerized cognitive batteries, biomarker and genetic tests, PET (FDG, amyloid and tau) and MRI scans and cerebral spinal fluid (CSF) collection for up to 5 years.
*currently recruiting non-Caucasian participants only for the cognitively normal cohort.
Efficacy, Safety and Tolerability of CK-2127107 in Patients With ALS (FORTITUDE-ALS)
The purpose of this study is to assess the effect of CK-2127107 versus placebo on respiratory function and other measures of skeletal muscle function in patients with ALS.
Are You a Candidate?
- Diagnosis of familial or sporadic ALS ≤ 24 months prior to screening
- Upright Slow Vital Capacity (SVC) ≥ 60% of predicted for age, height, and sex at screening
- Able to swallow tablets
- A caregiver (if one is needed)
- Able to perform reproducible pulmonary function tests
- Pre-study clinical laboratory findings within the normal range or, if outside the normal range, deemed not clinically significant by the Investigator
- Male patients who have not had a vasectomy and confirmed zero sperm count must agree after receiving the first dose of study drug until 10 weeks after the last dose to either use acceptable methods of contraception or abstain from sex
- Female patients must be post-menopausal or sterilized or must not be breastfeeding, have a negative pregnancy test, have no intention to become pregnant during the study and use acceptable methods of contraception or abstain from heterosexual intercourse from Screening until 10 weeks after last dose of study drug
- Patients must be either on riluzole for at least 30 days prior to screening or have not taken riluzole for at least 30 days prior to screening and not planning to start riluzole during the course of the study.
- At the time of screening, any use of non-invasive ventilation (NIV), e.g. continuous positive airway pressure [CPAP], noninvasive bi-level positive airway pressure [NPPV] or noninvasive volume ventilation [NVV]for any portion of the day, or mechanical ventilation via tracheostomy, or on any form of oxygen supplementation
- Neurological impairment due to a condition other than ALS
- Presence at screening of any medically significant cardiac, pulmonary, GI, musculoskeletal, or psychiatric illness that might interfere with the patient’s ability to comply with study procedures or that might confound the interpretation of clinical safety or efficacy data
- Has taken any investigational study drug within 30 days or five half-lives of the prior agent, whichever is longer, prior to dosing
- Known to have received CK-2127107 or tirasemtiv in any previous clinical trial
- Has received or is considering receiving during the course of the study any form of stem cell therapy for the treatment of ALS
- Has received or is considering receiving during the course of the study any form of gene therapy for the treatment of ALS
- Has received or is considering obtaining during the course of the study a diaphragmatic pacing system
- History of substance abuse within the past 2 years
- Use of certain medications