Clinical Trials and Studies Winter 2011

Article Highlights:

New and ongoing clinical trials, as of December 2010:

by Quest Staff on January 1, 2011 - 1:50pm

QUEST Vol. 18, No. 1

Tadalafil being tested for skeletal-muscle effects in Becker MD

Researchers at Cedars-Sinai Medical Center in Los Angeles are testing the effects of tadalafil on blood flow in forearm muscles.

Tadalafil (Cialis), a phosphodiesterase 5 inhibitor that may improve blood flow to skeletal muscles, is being tested in an MDA-supported trial in 24 men ages 18-55 with Becker muscular dystrophy (BMD) at Cedars-Sinai Medical Center in Los Angeles. Cialis is approved by the U.S. Food and Drug Administration for treatment of erectile dysfunction. Participants must meet study criteria.

Contact Dominique Durant at (310) 248-8080 or Julie Groth at (310) 248-7641.

Sildenafil being tested for cardiac effects in DMD

Sildenafil (Revatio), a phosphodiesterase 5 inhibitor that may improve blood flow to the heart muscle, is being tested in 30 adolescents and men ages 15-50 with Duchenne muscular dystrophy (DMD) at Johns Hopkins University in Baltimore. Revatio is approved by the U.S. Food and Drug Administration for the treatment of pulmonary arterial high blood pressure. Under the brand name Viagra, sildenafil is approved to treat erectile dysfunction. Participants must meet study criteria.

Contact Genila Bibat at (443) 923-2778 or

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Acceleron testing ACE031 in DMD

Researchers at Johns Hopkins University are testing the cardiac effects of sildenafil in people with DMD.

Acceleron Pharma is testing its experimental drug ACE031 in 76 boys with Duchenne muscular dystrophy (DMD). The drug is designed to interfere with the actions of the naturally occurring protein myostatin, a limiter of muscle growth.

Participants must be at least 4 years old and meet other study criteria. There are five study sites, all in Canada. They’re located in Calgary, Alberta; Vancouver, British Columbia; Hamilton, Ontario; London, Ontario; and Ottawa, Ontario.

Contact Rhiannon Taranik at (519) 685-8441 or, or send e-mail to

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Exon-skipping drug AVI4658 led to dystrophin production with no immune response in DMD

The experimental drug AVI4658, being developed by AVI BioPharma to treat patients with Duchenne muscular dystrophy (DMD) with mutations in the area of exon 51 of the dystrophin gene, was apparently safe and led to substantial production of dystrophin protein in some participants in a trial conducted in the United Kingdom.

AVI BioPharma announced these results in October 2010 at a meeting of the World Muscle Society held in Kumamoto, Japan. Nineteen boys with dystrophin gene mutations in the area of exon 51 received weekly intravenous infusions of AVI4658 for 12 weeks and were followed for an additional 14 weeks. Muscle biopsies were taken before treatment and then at week 14, two weeks after the final infusion.

AVI4658 was well tolerated by all trial participants over the 26 weeks of the study. Three participants showed substantial levels of dystrophin-positive muscle fibers, with no apparent immune response to the newly made dystrophin protein.

AVI plans to continue developing AVI4658 for DMD, including testing it in the United States.

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DMD exon-skipping drug PRO051/GSK2402968 testing moving ahead

In October 2010, the Dutch biotech company Prosensa announced it had received 7.5 million pounds from the pharmaceutical company GlaxoSmithKline as a result of having received a successful safety review for PRO051/GSK2402968, an experimental compound design to skip exon 51 of the dystrophin gene. The drug, like AVI4658 (see previous item), is designed to treat patients with Duchenne muscular dystrophy (DMD) who have mutations in or around exon 51. The safety data are from a study of 12 people with DMD who received weekly subcutaneous injections of the drug in Europe. PRO051/GSK2402968 is now in a phase 2 study in children with DMD in Europe, slated to end in November 2011.

It’s also being tested in a phase 1 study at Nationwide Children’s Hospital in Columbus, Ohio, scheduled to be completed in January 2011. That trial includes 32 nonwalking boys with DMD who are at least 9 years old, have specific dystrophin gene mutations and meet other study criteria. The study coordinator for the Nationwide trial is Xiomara Quintero Rosales, who can be reached at (614) 722-6961 or However, the study is unlikely to be open to new participants in 2011.

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DMD exon-skipping drug drug PRO044 being tested in Europe

Prosensa has developed an experimental exon-skipping agent to treat patients with Duchenne muscular dystrophy (DMD) who have the potential to benefit from skipping exon 44 of the dystrophin gene. This study includes 12 people with DMD who have mutations in or around exon 44, are 5-16 years old and meet other study criteria. This study is expected to end in December 2011.

Prosensa is conducting laboratory studies to develop compounds to skip exons 45, 52, 53 and 55 of the dystrophin gene.

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DMD Clinical Research Network studying heart effects in DMD, BMD

The MDA Clinical Research Network for Duchenne muscular dystrophy (DMD), with sites in Boston, Minneapolis, St. Louis, Columbus, Ohio and Sacramento, Calif., is recruiting for two studies.

One study is to determine the “natural history” of cardiac disease in DMD and Becker muscular dystrophy (BMD), both of which result from deficiencies of the dystrophin protein; to compare the cardiac and skeletal-muscle effects of dystrophin deficiency over time; and to correlate the cardiac effects with specific dystrophin gene mutations. The investigators hope to recruit 800 participants with DMD or BMD with a documented mutation of the dystrophin gene who can cooperate with cardiac and skeletal-muscle testing. The study will end in July 2012.

Another study will compare two cardiac drugs, losartan (Cozaar) and lisinopril (Prinivil, Zestril), for their effects on cardiac and skeletal muscle in DMD. Both drugs, now on the market to treat certain types of cardiac problems, interfere with the actions of angiotensin, a protein that causes blood vessels to constrict. In this double-blinded study, the investigators seek to enroll 150 participants with DMD who have a mutation in the dystrophin gene that does not allow any dystrophin production or who have a muscle biopsy showing less than 5 percent of the normal dystrophin level; who have a cardiac “ejection fraction” of less than 55 percent; who can cooperate for study testing; and who are not taking any heart medication at the start of the study. Participants will be seen every four months for one year.

For information about either study, contact Laurence Viollet at Nationwide Children’s Hospital in Columbus, Ohio, at (614) 355-2695 or

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Access to ataluren provided to US trial participants

The experimental drug ataluren developed by PTC Therapeutics has shown some promise at the lower of two doses tested in boys with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) whose disease results from a premature stop codon mutation (also called a “nonsense” mutation) in the dystrophin gene. (See Stop codon read-through: Less may be more with ataluren, Quest Research Updates, July-September 2010.)

Ataluren (formerly called PTC124) is designed to coax the cell machinery to “read through” premature molecular stop signals that would otherwise stop protein synthesis for dystrophin, the muscle protein missing in DMD. The goal is for functional dystrophin protein to be produced.

Final analysis of data from PTC Therapeutics’ phase 2b clinical trial showed that ataluren slowed the loss of walking ability in patients with nonsense-mutation DMD and BMD at the lower of two doses tested, although not at the higher dose. In a test of how far participants could walk in six minutes, those treated with the lower dose of ataluren walked approximately 30 meters (97 feet) further than those treated with a placebo.

In December 2010, PTC said it is “committed to addressing requests for access to ataluren for previous clinical trial patients.”

After holding discussions with the U.S. Food and Drug Administration, PTC is providing access to ataluren through a program similar to an open-label safety study, in that everyone will receive ataluren (no one will receive a placebo), and safety data will be collected.

Only former trial participants from PTC’s DMD/BMD trials at U.S. sites are eligible for the program. For details, contact Diane Goetz, PTC’s director of patient and professional advocacy at

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Researchers encouraged by LGMD gene therapy trial results

An MDA-supported, phase 1 study of gene therapy for the type 2D form of limb-girdle muscular dystrophy (LGMD2D) showed sustained production of the needed alpha-sarcoglycan protein from transferred alpha-sarcoglycan genes in two out of three trial participants six months after injection of the genes into a foot muscle.

The new results follow earlier findings from 2009 which showed alpha-sarcoglycan protein production from transferred genes in the first three participants in this trial at either six weeks or three months after the gene transfer.

A cautionary note is that one of the three participants whose foot muscle was examined at six months post-injection showed evidence of an immune response against the viral vehicle used to deliver the gene. The researchers say a previous viral infection may have caused this unwanted response.

Neurologist Jerry Mendell at Nationwide Children’s Hospital in Columbus, Ohio, coordinated the study team, which published its findings online Oct. 28, 2010, in Annals of Neurology. Mendell, who received MDA support for this study, directs the MDA clinic and the Center for Gene Therapy at Nationwide.

The investigators say a trial involving whole-limb delivery of alpha-sarcoglycan genes to patients with LGMD2D is on the drawing board.

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Valproic acid, carnitine not helpful in nonwalking young children with SMA

Six months of treatment with valproic acid and carnitine failed to benefit nonwalking children ages 2 to 8 with spinal muscular atrophy (SMA) in a 61-person trial. Excessive weight gain was the most frequent treatment-related adverse event.

Kathryn Swoboda at the University of Utah School of Medicine in Salt Lake City, with colleagues there and at several other institutions, published their results online Aug. 19, 2010, in PLoS One.

A valproic acid and carnitine combination treatment is being studied in infants with SMA, and valproic acid alone is being tested in walking adults with SMA. Neither of these trials is recruiting new participants.

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New $1.4 million MDA grant propels experimental SMA drug toward human trials

MDA has awarded a $1.4 million grant to Repligen Corp. aimed at advancing the company’s experimental drug RG3039 to human clinical trials for treatment of spinal muscular atrophy (SMA). The new grant was awarded through MDA’s translational research program, which works to move promising drugs from the laboratory to the clinic.

In completed studies, RG3039 increased cellular levels of the SMN protein, deficient in SMA, in mouse models of the disease and in cells taken from SMA-affected individuals. It’s expected that such increased SMN protein production will provide therapeutic benefits for people with SMA.

Repligen was completing the nonhuman studies necessary for the U.S. Food and Drug Association (FDA) to consider approving testing of RG3039 in humans. Once it receives FDA approval, the company plans to conduct two phase 1 clinical trials designed to test RG3039’s safety, tolerability and pharmacokinetics (the way the drug behaves in the body).

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Survey on reproductive choices in families with SMA open until mid-January

Investigators at Indiana University are seeking to understand factors that influence parents’ reproductive decisions after they have had a child with spinal muscular atrophy (SMA). The online survey, which is designed to be completed in about 10 minutes, is available to biological parents of a child with SMA until Jan. 15, 2011.

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Leuprorelin does not improve swallowing in SBMA

Reducing testosterone levels with the drug leuprorelin in a large-scale trial in men with spinal-bulbar muscular atrophy (SBMA), also called Kennedy disease, did not significantly affect swallowing function, despite earlier indications that it might improve this aspect of the disease. Gen Sobue at Nagoya (Japan) University, and colleagues, published the findings online in Lancet Neurology Aug. 4, 2010.

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Two-drug combo helpful in FA

Results from a clinical trial conducted in Spain involving 20 people with Friedreich’s ataxia (FA) showed a combination therapy using the drugs idebenone and deferiprone stabilized neurological function and reduced abnormal heart-muscle enlargement when taken for 11 months.

Idebenone is an antioxidant and is thought to help cells increase energy production. 

Deferiprone reduces iron levels in the body.

Daniel Velasco-Sanchez at the University of Barcelona (Spain), and colleagues, published their results online Sept. 24, 2010, in the journal Cerebellum.

Study seeks people with unclassified muscle diseases

Investigators at New York University are seeking people who are at least 18 years old 

and have a form of muscular dystrophy or myopathy (muscle disease) that has been difficult to classify. The investigators speculate that some undiagnosed muscle problems may be late-onset Pompe disease (acid maltase deficiency), which can be treated with enzyme replacement therapy.

The investigators will arrange a telephone discussion with each prospective participant, after which they may request further information before making a final decision on eligibility for enrollment. Those who do enroll in the study will be asked to provide a blood sample to evaluate acid maltase enzyme levels. Each participant will receive a kit to expedite the sample collection (which can be done locally) and shipping of the sample. Participants will be asked to fill out a questionnaire, and medical records will be requested. No travel is required. All costs are covered by the study.

Contact Edward Nunziato at New York University School of Medicine at

Editor's note 7/15/11: The study of unclassified muscle diseases closed to enrollment of new participants July 15, 2011.

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