Clinical Trial Descriptions
GENE THERAPY
Because a faulty gene causes cystic fibrosis (CF), adding normal copies of the gene to cells should correct these cells and ultimately cure the disease.
Compacted DNA (Copernicus Therapeutics) – Non-viral compacted DNA (PLASmin™) is being used to introduce normal copies of the gene into CF airways. A Phase 1a trial demonstrated chloride current changes in the noses of CF patients, but no evidence of gene expression. The gene therapy product is being reformulated prior to additional clinical trials in an attempt to improve the amount and duration of gene expression.
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PROTEIN ASSIST/REPAIR
This therapy is designed to correct the function of the defective CFTR protein made by the CF gene to allow chloride and sodium (salt) to move properly in cells lining the lungs and other organs.
- PTC 124 (PTC Therapeutics) – PTC 124 is a novel, small molecule compound, that promotes the read-through of premature truncation codons in the CFTR mRNA. It has been demonstrated to be safe, orally available and well-tolerated in a Phase 1 single-dose trial in healthy volunteers. A Phase 2 trial in CF patients conducted in the U.S. and Israel demonstrated safety and encouraging biological results.
- VX-770 (Vertex Pharmaceuticals) – VX-770 is a new compound called a "potentiator" that may act upon the CFTR protein and help to open the chloride channel in CF cells. Phase 1 dosing has been completed in patients. Researchers are evaluating results and a Phase 2 trial has begun in CF patients.
- Curcumin (Seer Pharmaceuticals) – Curcumin is seeking to correct the abnormal processing of CFTR in the cell. It appears to work in some strains of CF mice but not all. A previous Phase 1 trial in CF patients did not show correction of CFTR. A follow-on study at a higher dose is ongoing to confirm these findings.
- GSNO (Nitrox, LLC) – S-Nitrosoglutathione (GSNO) levels are low in the lungs of CF patients. GSNO has been shown to promote trafficking of the Delta-F508 CFTR in some, but not all, tests on cultured cells. Nitrox LLC is developing inhaled GSNO for CF and is presently carrying out required preclinical safety studies, as well as formulation studies.
- VX-809 (Vertex Pharmaceuticals) – VX-809 is a "corrector" that helps to move the defective CFTR protein to the proper place in the airway cell membrane and to improve its function as a chloride channel. A Phase 1 dosing trial has begun in healthy volunteers.
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RESTORE SALT TRANSPORT
The goal of this approach is to hydrate thick CF mucus in the lungs by correcting the amount of salt (sodium & chloride) along the cell surface.
Denufosol (Inspire Pharmaceuticals, Inc.) – Denufosol is being usedd to correct the ion transport defect in CF. A recently completed Phase 2 trial to determine the effect of drug on pulmonary function in CF patients demonstrated efficacy. The first of two FDA-mandated Phase 3 trials has completed enrollment. The second Phase 3 trial will be a multi-national one and is scheduled to begin in 2008.
SPI-8811 (Sucampo Pharmaceuticals, Inc.) – This oral agent is believed to bypass transport defect of chloride ions. Initial Phase 2a trial evaluating safety and efficacy. Thirty patients have been recruited.
- Moli (Lantibio, Inc.) – Inhaled Moli1901 is believed to affect the ion transport defect in CF patients. A Phase 1 trial has demonstrated safety and a placebo-controlled, multi-dose, dose-ranging Phase 2 trial in Europe demonstrated positive changes in pulmonary function with highest dose.
- Gilead GS9411 (now Gilead Sciences; formerly Parion ) – An earlier compound (Parion 552) has been used to develop proof-of-concept. Gilead GS9411 acts by blocking sodium absorption.
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MUCUS TREATMENT
The following studies are being evaluated for their effectiveness in thinning and clearing the thick mucus from the airways.
Pulmozyme (Genentech) – Pulmozyme was the first drug developed specifically for CF in 30 years and was approved by the FDA in 1993; it became available in 1994. It is currently being used by more than 18,000 U.S. patients. Clinical trials were conducted in the Foundation's care center network.
Hypertonic Saline – A CF Foundation-supported study in Australia showed hypertonic saline to be safe and effective in adults with CF, helping clear mucus and leading to better lung function. The drug is now being evaluated for safety and effectiveness in younger people with CF.
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ANTI-INFLAMMATORY
Anti-inflammatory drugs are being studied for their ability to reduce inflammation in CF lungs.
Oral N-acetylcysteine (BioAdvantex Pharma, Inc.) – An antioxidant, oral N-acetylcysteine replenishes glutathione levels in neutrophils. A placebo-controlled 12-week study at Stanford Univ. demonstrated decreases in inflammatory cells in lung and positive indications of changes in pulmonary function.
DHA (Univ. of Massachusetts, CFFT-supported as clinical research grant) – People with CF appear to have lower than normal levels of DHA, a fatty acid that may be important to protecting the body against inflammation. A lack of DHA in people with CF may contribute to increased inflammation in the lungs. A pilot study in 120 newly diagnosed patients at 16 CF care centers began in 2003 to examine the effect of infant formula fortified with DHA on the pathogenesis of CF .
Low-dose Methotrexate; Pioglitazone; Hydroxychloroquine – These approved therapies (approved for non-CF indications) are being evaluated in exploratory Phase 1 trials in CF to determine if they are tolerated and if anti-inflammatory effects are seen.
Simvastatin (ZocorTM) (Merck & Co., Inc.) – A HMG-CoA reductase inhibitor, simvastatin is thought to increase nitric oxide (NO) production in cultured CF epithelial cells. Researchers are evaluating whether simvastatin increases exhaled NO production in CF patients, synthesis of pro-inflammatory cytokines and whether measures of inflammation in the upper respiratory tract correlate with those from the lower respiratory tract.
Inhaled Glutathione A Phase 1 trial of inhaled glutathione began in Germany in mid-2007.
HE-2000 (Hollis-Eden Pharmaceuticals) – A hormone that may help to regulate the immune system, which is in “overdrive” in CF lungs. An oral immune-regulating hormone is in preclinical testing. Clinical trials could begin in 2008.
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ANTI-INFECTIVE
The following drugs are being studied for their effectiveness in fighting lung infections for people with CF.
TOBI (Novartis Pharmaceuticals) – This CFF/Children’s Hospital, Seattle-developed aerosol antibiotic was licensed to Chiron and received FDA approval in 1998. Currently being used by more than 15,000 patients worldwide. The benefit at first sign(s) of Pseudomonas infection is being evaluated in a Phase 4 EPIC study which began in the 4th quarter of 2004.
Azithromycin (Pfizer, Inc.) – In patients with chronic PA, this oral antibiotic improved lung function and weight gain, and decreased hospitalization rate. A large-scale trial was completed in 2002. Two follow up studies are in progress.
Aztreonam (Gilead Sciences) – Multiple Phase 3 trials of the aerosolized form of aztreonam, a widely used IV antibiotic in CF, have been completed and the FDA is reviewing all data. This antiobiotic may be ready for market in 2008.
TIP (TOBI Inhaled Powder) (Novartis Pharmaceuticals) – Developing TOBI as a powder to enable a faster, more convenient dosing regimen is being studied. Dosing of TIP will take a fraction of the time of liquid TOBI. A Phase 3 trial began in 2006.
Bayer-Inhaled Ciprofloxacin (Bayer Schering Pharma) An inhaled version of the antibiotic ciprofloxacin is being developed for treatment of airway infections. A small Phase 2 study in Germany is underway.
- SLIT-amikacin (Transave, Inc.) – This is a liposomal formulation of the antibiotic amikacin. Animal model studies have shown it to decrease the Pseudomonas aeruginosa burden in the lung. A Phase 1/2 trial in Europe has completed enrollment. A Phase 2 trial began in the United States in 2007.
- Kalobios KB001 (Kalobios Pharmaceuticals) – A Phase I clinical trial has been initiated to test the safety of this antibody approach for the treatment of Pseudomonas aeruginosa lung infections.
Pseudomonas Vaccines – Several companies are in preclinical development of pseudomonas vaccines. The development of Berna Biotech’s product, which was in Phase 2 testing, has been halted due to lack of efficacy.
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LUNG TRANSPLANT DRUGS
A lung transplant drug is currently being evaluated to help improve the chances of successful transplants.
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NUTRITIONAL SUPPLEMENTS
Nutritional supplements help improve the body’s ability to ward off the effects of CF.
ALTU-135 (formerly TheraCLEC Total; Altus Pharmaceuticals, Inc.) – A Phase 1 study did not identify safety concerns for this non-porcine pancreatic enzyme replacement. A Phase 2 trial has been completed, demonstrating safety and efficacy and a Phase 3 trial began in May 2007.
Yasoo (Yasoo Health, Inc.) – An oral antioxidant vitamin formulation specifically for CF patients. A Phase 1 trial has been completed. A clinical trial to assess the safety and ability of this formulation increase blood levels of antioxidants, normalize plasma levels of fat-soluble vitamins, improve pulmonary function and improve growth parameters began in 2007.
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