Healthcare Industry News: PROGRESS study
News Release - April 13, 2010
Baxter and New York-Presbyterian/Weill Cornell Announce 18-Month Data from Phase II Study of GAMMAGARD in Patients with Alzheimer's DiseaseOngoing Phase III study currently accepting new participants
Baxter to initiate a second Phase III study
TORONTO--(HSMN NewsFeed)--Baxter International Inc. (NYSE: BAX ) and New York-Presbyterian Hospital/Weill Cornell Medical Center today announced results of an 18-month Phase II clinical study of GAMMAGARD LIQUID and GAMMAGARD S/D [Immune Globulin Intravenous (Human)] (marketed as KIOVIG outside of the U.S.) for mild-to-moderate Alzheimer’s disease. This marked the first announcement of clinical trial results measuring function and cognition in patients who received uninterrupted GAMMAGARD for a period of 18 months.
The study measured function using the Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change rating (ADCS-CGIC) and measured cognition using the Alzheimer’s Disease Assessment Scale-Cognitive Subscale score (ADAS-Cog). After 18 months, patients (n=14) who received GAMMAGARD continuously averaged approximately 1.36 points higher than patients (n=7) who initially received placebo (-0.64 vs. -2.0, p=0.011) on the ADCS-CGIC. Patients (n=14) who received GAMMAGARD continuously declined by approximately 9.15 fewer ADAS-Cog points than patients (n=6) who initially received placebo (approximately 6 point decline vs. 15 point decline, p=0.013).
The data are being presented at the American Academy of Neurology (AAN) annual meeting in Toronto by the principal investigator for the trial, Dr. Norman Relkin, and Dr. Diamanto Tsakanikas. Dr. Relkin is the director of the Memory Disorders Program and a behavioral neurologist and neuroscientist at the New York-Presbyterian Hospital/Weill Cornell Medical Center, and associate professor of clinical neurology at Weill Cornell Medical College. Dr. Tsakanikas is a clinical assistant attending neuropsychologist at New York-Presbyterian Hospital/Weill Cornell Medical Center and instructor of neuropsychology in the Department of Neurology & Neuroscience at Weill Cornell Medical College. The study was supported by Baxter, the Citigroup Foundation, and The Clinical Translational Science Center (CTSC) of Weill Cornell Medical College.
Being presented for the first time, MRI analyses showed that patients who received GAMMAGARD continuously for 18 months experienced decreased mean annual ventricular enlargement rates in their brains (6.7%), compared to control patients who initially received placebo (12.3%, p=0.048). The decreased rates of ventricular enlargement correlated with clinical outcomes in patients who received continuous GAMMAGARD for 18 months, as measured using the ADCS-CGIC (r= 0.523, p= 0.018) and the ADAS-Cog (r=0.64, p=0.0041). In addition, patients who received GAMMAGARD continuously for 18 months experienced lower mean annual whole brain atrophy rates (-1.58%), compared to control patients who initially received placebo (-2.24%, p=NS). The decreased rates of whole brain atrophy correlated with clinical outcomes in patients who received continuous GAMMAGARD for 18 months, as measured using the ADCS-CGIC (r= 0.64, p= 0.0041) and the ADAS-Cog (r=0.42, p=0.076).
“The cognitive and functional outcomes and neuroimaging results from this 18-month Phase II study in participants receiving GAMMAGARD continuously clearly support continued evaluation for Alzheimer's disease in a larger number of patients,” said Dr. Paul Aisen, director of the Alzheimer’s Disease Cooperative Study. “The important next step is to fully enroll and complete the ongoing Phase III study of GAMMAGARD, in hope of confirming these Phase II findings and fully understanding GAMMAGARD’s potential benefit in Alzheimer’s disease.”
The ongoing Phase III study of GAMMAGARD, called the Gammaglobulin Alzheimer’s Partnership (GAP) Study, is designed to evaluate the potential of GAMMAGARD for mild-to-moderate Alzheimer’s disease. The study includes 35 actively enrolling sites at leading academic centers in the United States that are members of The Alzheimer’s Disease Cooperative Study (ADCS), with an additional 12 sites pending in the U.S. and Canada. Study participants will be evaluated on clinical scales for cognition and function over 18 months. Biomarker and neuroimaging tests will be performed in order to measure GAMMAGARD’s potential effect on disease progression. Alzheimer’s patients and their caregivers can find study details and learn more about participation by visiting www.GAPSTUDY.com or calling 1-877-55-GAPSTUDY (1-877-554-2778). The study is sponsored by Baxter and partially funded by the National Institutes of Health (NIH) through the Alzheimer’s Disease Cooperative Study (ADCS).
Baxter plans to initiate a second, concurrent Phase III study of GAMMAGARD for mild-to-moderate Alzheimer’s disease to confirm the Phase II results in more patients. The Phase II results represent the first study in Alzheimer’s disease where all three measures – cognitive, functional and neuroimaging – had positive data and were statistically significant.
“Baxter is encouraged by the 18-month Phase II results for GAMMAGARD for Alzheimer’s disease. Based on the strength of these data, we plan to initiate a second Phase III study of GAMMAGARD for Alzheimer’s disease,” said Hartmut Ehrlich, M.D., vice president of research and development for Baxter BioScience. “The new study will collect additional evidence to support GAMMAGARD’s use in mild-to-moderate Alzheimer’s disease and, with our ongoing Phase III study, support filing for registration in this indication. We will work closely with FDA on appropriate next steps and look forward to making continued PROGRESS studying GAMMAGARD’s potential benefit in Alzheimer’s disease and other neurology indications.”
Baxter’s commitment to advancing the scientific and clinical knowledge around GAMMAGARD in several neurological applications includes multiple late-stage clinical trials. In addition to the ongoing Phase III trial studying GAMMAGARD LIQUID in Alzheimer’s disease, Baxter is currently enrolling patients into a Phase III trial studying GAMMAGARD LIQUID in multifocal motor neuropathy (MMN). A Phase III trial studying GAMMAGARD LIQUID in chronic inflammatory demyelinating polyneuropathy (CIDP) is planned to begin later this year.
Phase II Study Design
In the double-blind, placebo-controlled Phase II study, 24 patients in the U.S. with mild-to-moderate Alzheimer’s disease were randomly assigned to receive GAMMAGARD (16 patients), or saline placebo (8 patients) for six months. After six months, the group initially receiving placebo subsequently received various doses of GAMMAGARD while the other 16 patients had uninterrupted GAMMAGARD at the initially assigned dose. The study included a comparison of four dosing regimens of GAMMAGARD, with doses ranging from 0.2 g/kg every two weeks to 0.8 g/kg every four weeks.
Cognitive, behavioral and functional measures were collected at baseline and every three months thereafter. The primary endpoints of the Phase II trial were global function, as assessed by the ADCS-CGIC, and cognitive function, as measured by the ADAS-Cog. Safety and tolerability of GAMMAGARD in Alzheimer’s patients were also assessed relative to placebo. Secondary endpoints included effects on neuroimaging and biomarkers related to beta amyloid, a peptide related to Alzheimer’s disease.
Phase III Study Design
The ongoing Phase III trial is a prospective, 18-month, randomized, double-blind, placebo-controlled, two dose-arm, parallel groups in 360 subjects of both genders, ages 50 to 89 years old, with Alzheimer’s dementia of mild-to-moderate severity. The study will evaluate whether intervention with GAMMAGARD LIQUID results in a significantly slower rate of decline of cognitive and other functions compared to placebo. This trial is expected to be the first of two pivotal Phase III trials required to support filing for regulatory approval for GAMMAGARD LIQUID for Alzheimer’s disease.
Efficacy will be assessed by two co-primary endpoints: global clinical outcome as assessed by the Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change rating (ADCS-CGIC), and cognitive outcomes using the Alzheimer’s Disease Assessment Scale-Cognitive Subscale score (ADAS-Cog).
Secondary endpoints to be assessed include behavioral, functional and quality of life outcome measures. Other study endpoints will include several plasma, cerebrospinal fluid, and neuroimaging biomarkers to assess disease progression and response to GAMMAGARD.
About GAMMAGARD LIQUID
GAMMAGARD LIQUID is indicated for the treatment of primary immunodeficiency disorders associated with defects in humoral immunity. These include, but are not limited to, congenital X-linked agammaglobulinemia, common variable immunodeficiency, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.
Important Risk Information
GAMMAGARD LIQUID is contraindicated in patients with known anaphylactic or severe hypersensitivity responses to Immune Globulin (Human). Patients with severe selective IgA deficiency (IgA < 0.05 g/L) may develop anti-IgA antibodies that can result in a severe anaphylactic reaction.
Immune Globulin Intravenous (Human) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients with any degree of pre-existing renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Especially in such patients, IGIV products should be administered at the minimum concentration available and the minimum rate of infusion practicable. While these reports of renal dysfunction and acute renal failure have been associated with the use of many of the licensed IGIV products, those containing sucrose as a stabilizer accounted for a disproportionate share of the total number.
Glycine, an amino acid, is used as a stabilizer. GAMMAGARD LIQUID does not contain sucrose.
GAMMAGARD LIQUID is made from human plasma. It may carry a risk of transmitting infectious agents, viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
Components used in the packaging of this product are latex-free.
Thrombotic events have been reported in association with IGIV. Patients at risk may include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, and/or known or suspected hyperviscosity, hypercoagulable disorders, and prolonged periods of immobilization.
IGIV products can contain blood group antibodies that may cause a positive direct antiglobulin reaction and, rarely, hemolysis.
Aseptic meningitis syndrome (AMS) has been reported to occur infrequently in association with IGIV treatment. Discontinuation of IGIV treatment has resulted in remission of AMS within several days without sequelae.
Various mild and moderate reactions, such as headache, fever, fatigue, chills, flushing, dizziness, urticaria, wheezing or chest tightness, nausea, vomiting, rigors, back pain, chest pain, muscle cramps, and changes in blood pressure may occur with infusions of Immune Globulin Intravenous (Human).
For full prescribing information, please visit: http://www.baxter.com/products/biopharmaceuticals/downloads/gamliquid_PI.pdf.
About New York-Presbyterian Hospital/Weill Cornell Medical Center
New York-Presbyterian Hospital/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital New York-Presbyterian and Weill Cornell Medical College, the medical school of Cornell University. New York-Presbyterian/Weill Cornell provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine, and is committed to excellence in patient care, education, research and community service. Weill Cornell physician-scientists have been responsible for many medical advances — from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial for gene therapy for Parkinson's disease, the first indication of bone marrow's critical role in tumor growth, and, most recently, the world's first successful use of deep brain stimulation to treat a minimally-conscious brain-injured patient. New York-Presbyterian, which is ranked sixth on the U.S. News & World Report list of top hospitals, also comprises New York-Presbyterian Hospital/Columbia University Medical Center, Morgan Stanley Children's Hospital of New York-Presbyterian, New York-Presbyterian Hospital/Westchester Division and New York-Presbyterian Hospital/The Allen Pavilion. Weill Cornell Medical College is the first U.S. medical college to offer a medical degree oversees and maintains a strong global presence in Austria, Brazil, Haiti, Tanzania, Turkey and Qatar. For more information, visit www.nyp.org and www.med.cornell.edu.
Baxter International Inc., through its subsidiaries, develops, manufactures and markets products that save and sustain the lives of people with hemophilia, immune disorders, infectious diseases, kidney disease, trauma, and other chronic and acute medical conditions. As a global, diversified healthcare company, Baxter applies a unique combination of expertise in medical devices, pharmaceuticals and biotechnology to create products that advance patient care worldwide.
This release includes forward-looking statements concerning GAMMAGARD LIQUID as a potential treatment of Alzheimer’s disease, including expectations with respect to the related Phase III trials. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: timely submission and approval of anticipated regulatory filings; the ability of the company to enroll a sufficient number of qualified participants in the required Phase III trials; the ability of the company to otherwise successfully initiate both required Phase III trials; the ability of the company to complete both required Phase III trials on a timely basis; clinical results demonstrating the safety and efficacy of the product as a potential treatment for Alzheimer’s disease; and other risks identified in the company's most recent filing on Form 10-K and other SEC filings, all of which are available on the company's website. The company does not undertake to update its forward-looking statements.
Source: Baxter International
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