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.
The CENTAUR trial will be a 2:1 (active:placebo) randomized, double-blind, placebo-controlled Phase II trial to evaluate the safety and efficacy of AMX0035 for the treatment of ALS.
AMX0035 is a combination therapy designed to reduce neuronal death through blockade of key cellular death pathways originating in the mitochondria and endoplasmic reticulum (ER). This clinical trial is designed to demonstrate that treatment is safe, tolerable, and able to slow decline in function as measured by the ALSFRS-R.
The trial will also assess the effects of AMX0035 on muscle strength, vital capacity, and biomarkers of ALS including markers of neuronal death and neuroinflammation.
Are You a Candidate?
- Male or female, aged 18-80 years of age
- Sporadic or familial ALS diagnosed as definite as defined by the World Federation of Neurology revised El Escorial criteria
- Less than or equal to 18 months since ALS symptom onset
- Capable of providing informed consent and following trial procedures
- Slow Vital Capacity (SVC) >60% of predicted value for gender, height, and age at the Screening Visit
- Subjects must either not take riluzole or be on a stable dose of riluzole for at least 30 days prior to the Screening Visit. Riluzole-naïve subjects are permitted in the study
- Women of child bearing potential (e.g. not post-menopausal for at least one year or surgically sterile) must agree to use adequate birth control for the duration of the study and 3 months after last dose of study drug. Women must not be planning to become pregnant for the duration of the study and 3 months after last dose of study drug
- Men must agree to practice contraception for the duration of the study and 3 months after last dose of study drug. Men must not plan to father a child or provide for sperm donation for the duration of the study and 3 months after last dose of study drug
- Presence of tracheostomy
- Exposure to PB, TUDCA or UDCA within 3 months prior to the Screening Visit or planning to use these medications during the course of the study
- History of known allergy to PB or bile salts
- Abnormal liver function defined as AST and/or ALT > 3 times the upper limit of the normal
- Renal insufficiency as defined by a serum creatinine > 1.5 times the upper limit of normal
- Poorly controlled arterial hypertension (SBP>160mmHg or DBP>100mmHg) at the Screening Visit
- Pregnant women or women currently breastfeeding
- History of cholecystectomy
- Biliary disease which impedes biliary flow including active cholecystitis, primary biliary cirrhosis, sclerosing cholangitis, gallbladder cancer, gallbladder polyps, gangrene of the gallbladder, abscess of the gallbladder
- History of Class III/IV heart failure (per New York Heart Association – NYHA)
- Severe pancreatic or intestinal disorders that may alter the enterohepatic circulation and absorption of TUDCA including biliary infections, pancreatitis and ileal resection
- The presence of unstable psychiatric disease, cognitive impairment, dementia or substance abuse that would impair ability of the subject to provide informed consent, according to Site Investigator judgment
- Clinically significant unstable medical condition (other than ALS) that would pose a risk to the subject if they were to participate in the study
- Active participation in an ALS clinical trial evaluating a small molecule within 30 days of the screening visit
- Exposure at any time to any biologic under investigation for the treatment of subjects with ALS (off-label use or investigational) including cell therapies, gene therapies, and monoclonal antibodies
- Implantation of Diaphragm Pacing System (DPS)
Transsphenoidal Extent of Resection Study (TRANSSPHER)
The treatment of choice for most patients with symptomatic nonfunctioning pituitary adenomas is transsphenoidal surgery to improve vision by decompression of the optic chiasm, to prevent the development of endocrine dysfunction, and to treat neurological symptoms such as headache or cranial neuropathies caused by the tumor. The most widely accepted surgical technique is microscopic transsphenoidal surgery, in which an operating microscope is used by the surgeon to provide surgical visualization and a nasal speculum is used to maintain the operative corridor. [1-4] Recently, fully endoscopic transsphenoidal surgery, in which surgical visualization is achieved using an endoscope, has been adopted by many pituitary surgeons because the technique offers superior panoramic and angled visualization of the surgical target and may permit greater tumor resection. [5-10] There is a vigorous debate in the neurosurgical community about the relative merits of the microscopic and endoscopic techniques. Proponents of the endoscopic technique argue that the superior visualization permits more aggressive tumor resection and better preservation of the normal pituitary gland. Proponents of the microscopic technique argue that it permits shorter operative times, results in similar surgical outcomes, and has a lower complication rate.
Despite the adoption of fully endoscopic surgery by many surgeons, no prospective studies have compared the extent of tumor resection (EOR) between microscopic and endoscopic approaches. Numerous retrospective studies have established the efficacy of each approach, but only a few studies present comparative data.[11-13] Recently, McLaughlin et al. noted that the addition of endoscopy to microscopic pituitary surgery enhances tumor removal, particularly in patients with tumors greater than 20 mm in diameter.  This study raises the intriguing possibility that certain subgroups of patients (e.g. patients with larger tumors) may benefit from endoscopic surgery. In patients with smaller tumors with no cavernous sinus invasion, others have shown that the techniques achieve similar EOR.  That endoscopy may permit more complete tumor resections is a testable hypothesis.