Rare Disease Report

Cytokinetics Begins Enrollment for Spinal Muscular Atrophy Clinical Trial

JANUARY 05, 2016
Rebekah Harrison
Open enrollment has begun for a phase 2 clinical trial testing Intercept’s CK-2127108, novel skeletal muscle troponin activator, in patients with spinal muscular atrophy (SMA). The clinical trial is designed to assess the effect of CK-2127107 on multiple measures of muscle function in both ambulatory and non-ambulatory patients with SMA.
Troponin activators increase muscle strength by amplifying the response of muscle when neural input is otherwise diminished. It slows the rate of calcium release from troponin C and sensitizes muscle to calcium.

What is Spinal Muscular Atrophy?

Spinal muscular atrophy (SMA) is a genetic disorder that affects the control of muscle movement. It is caused by the loss of motor neurons in the spinal cord. There are 4 types of SMA. Type 1 spinal muscular atrophy (also called Werdnig-Hoffman disease) is a severe form of the disorder that is evident at birth. Type 2 is characterized by muscle weakness that develops in children between ages 6 and 12 months. Children with type 2 can sit without support, although they may need help getting to a seated position. Individuals with this type of spinal muscular atrophy cannot stand or walk unaided. Type 3 spinal muscular atrophy (also called Kugelberg-Welander disease or juvenile type) has milder features that typically develop between early childhood and adolescence. Individuals with type 3 can stand and walk unaided but walking and climbing stairs may become increasingly difficult. Many affected individuals will require wheelchair assistance later in life. The signs and symptoms of type 4 spinal muscular atrophy often occur after age 30. Affected individuals usually experience mild to moderate muscle weakness, tremor, twitching, or mild breathing problems. Typically, only proximal muscles, such as the upper arms and legs, are affected.
Estimated incidence of SMA is 1 in 6,000 to 1 in 10,000 live births.
In collaboration with Astellas, Cytokinetics is developing CK-2127107 as a potential treatment for people living with SMA and certain other debilitating neuromuscular and non-neuromuscular diseases and conditions associated with skeletal muscle weakness and/or fatigue.

The Study

The primary objective of the double-blind, randomized, placebo-controlled clinical trial is to determine the potential biochemical and physiological effects of a suspension formulation of CK-2127107 following multiple oral doses in patients with Type 2, Type 3, or Type 4 SMA. Secondary objectives are to evaluate the safety, tolerability and pharmacokinetics of CK-2127107. The trial will enroll 72 patients in 2 sequential, ascending dose cohorts. Each cohort will be stratified by ambulatory versus non-ambulatory status to receive CK-2127107 dosed twice daily for 8 weeks. The second cohort of patients will receive 450 mg of CK-2127107 dosed twice daily or a lower dose, depending on the data from the first cohort. At the conclusion of the trial, approximately 24 patients will have been randomized to placebo, approximately 24 patients to 150 mg of CK-2127107 twice daily and approximately 24 patients to 450 mg of CK-2127107 twice daily (or a lower dose, pending the review of data from the first cohort). Multiple assessments of skeletal muscle function and fatigability will be performed including respiratory assessments, upper limb strength and functionality for non-ambulatory patients, as well as six-minute walk and timed-up-and-go for ambulatory patients.
“Initiating this first Phase 2 trial of CK-2127107 represents a major step forward given our interests to serve the many adolescents and adults who are living with SMA, a disorder with few treatment options,” said Robert I Blum, president and CEO of Cytokinetics. “We look forward to working closely with the investigators and clinical trial sites to evaluate the effects of our next-generation skeletal muscle activator, which we believe holds promise for the potential treatment of patients battling this devastating disease.”


Cytokinetics Announces Start of Phase 2 Clinical Trial of CK-2127107 in Patients with Spinal Muscular Atrophy [new release]. San Francisco, CA; Cytokinetics: January 4, 2016. http://www.nasdaq.com/press-release/cytokinetics-announces-start-of-phase-2-clinical-trial-of-ck2127107-in-patients-with-spinal-20160104-00182

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