A phase 2 clinical trial to test multiple doses of the experimental drug ISIS-SMNRx in infants with spinal muscular atrophy (SMA) has opened at four trial sites in the United States and Canada. Enrollment is expected to begin soon.
ISIS-SMNRx, developed by Isis Pharmaceuticals in Carlsbad, Calif., with Adrian Krainer at Cold Spring Harbor (N.Y.) Laboratory, is based on antisense technology. Antisense molecules are used to block segments of genetic instructions that create proteins, thereby changing the way these instructions are "read" by cells.
The study, which is expected to enroll eight infants with SMA, is designed to enable investigators to determine the optimal dose for a larger planned phase 2-3 study in infants, and also to provide safety and tolerability data on the experimental drug.
Kathie Bishop, executive director of clinical development at Isis, announced the opening of the trial April 23, 2012, at MDA's Scientific Conference in Washington, D.C.
In the most common form of SMA, genetic mutations in the SMN1 gene lead to a deficiency of SMN ("survival of motor neuron") protein. (Motor neurons are the muscle-controlling nerve cells that are lost in SMA.)
Children and adults with SMA carry one or more copies of a gene called SMN2, which is similar in makeup to SMN1. Usually, SMN protein made from the genetic instructions carried by the SMN2 gene is shorter, relatively nonfunctional and unstable compared to the protein made from SMN1 genes. Sometimes however, natural variations in the cellular protein-building process cause a different "readout" of the SMN2 genetic instructions; the result when this happens is production of full-length, functional SMN protein.
Antisense therapy aims to change the way cells process genetic instructions carried by SMN2, so that the result is always full-length SMN.
Each trial participant will receive multiple doses of ISIS-SMNRx, administered intrathecally three times over the duration of the trial. Investigators will assess safety, tolerability and pharmacokinetics.
In a completed phase 1 study in children with SMA ages 2 years to 14 years, ISIS-SMNRx was well-tolerated at all dose levels, with no safety or tolerability concerns. The injection method also was well-tolerated, and measurements of the drug in cerebral spinal fluid and blood showed that it reached expected levels.
ISIS-SMNRx currently is being tested in a study that is designed to examine the safety and tolerability of multiple doses of the drug given over a longer time period. This study is being conducted in children with SMA ages 2 years to 15 years, and is expected to be completed in 2013. Following that, Isis plans to conduct larger phase 3 studies, beginning in early 2014.
To participate in the trial, infants must be between the ages of 3 weeks and 7 months. In addition, they must:
Study site locations are:
Stanford University Medical Center — currently recruiting
Stanford, California, United States, 94305
Contact: Shirley Paulose, M.B.B.S., M.S.; 650-724-3792; email@example.com
Principal investigator: John Day, M.D.
Nemours Children's Hospital — not yet recruiting
Orlando, Florida, United States, 32827
Contact: Dawn Cook, R.N., M.S.N., C.C.R.C.; 407-650-7156; firstname.lastname@example.org
Principal investigator: Richard Finkel, M.D.
Columbia University Medical Center — not yet recruiting
New York, New York, United States, 10032
Contact: Rosangel Cruz, M.A., B.S.; 212-305-1336; email@example.com
Contact: Jonathan Marra, M.A.; 212-305-2461; firstname.lastname@example.org
Principal investigator: Claudia Chiriboga, M.D.
The Hospital for Sick Children (Sick Kids) — not yet recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Lynn MacMillan, R.N.; 416-813-7355; email@example.com
Principal investigator: Jiri Vajsar, M.D.
For more information
To learn more about the phase 2 trial and ISIS-SMNRx, read:
For additional questions, Isis Pharmaceuticals can be contacted at (800) 679-4747 or firstname.lastname@example.org.
About Clinical Trials
A clinical trial is a test, in humans, of an experimental treatment. Although it's possible that benefit may be derived from participating in a clinical trial, it's also possible that no benefit, or even harm, may occur.
MDA has no ability to influence who is chosen to participate in a clinical trial.
To learn more, see Learn About Clinical Studies and Being a Co-Adventurer, which is about neuromuscular disease clinical trials. To see a continuously updated database of clinical trials, go to ClinicalTrials.gov.