Mike
What trial are we awaiting the results on ?
Is there a second phase 2 trial done after the one below?
(Gaithersburg, MD) May 5, 1998 - Antex Biologics and SmithKline Beecham today announced the initial results of a Phase II clinical trial of Antex's Campylobacter vaccine. The trial demonstrated that the vaccine was safe, immunogenic and elicited intestinal and systemic immune responses associated with protection against disease. This trial also identified, for the first time, two immune correlates of protection that will be used to evaluate vaccine effectiveness in follow-on studies. These very encouraging results support continuing the development of Antex's Campylobacter vaccine and the basis for future field trials to evaluate its efficacy.
Dr. Vic Esposito, Chairman and CEO of Antex, said, "This clinical trial provided a unique opportunity to determine the immunological responses to Campylobacter infection and to assess the humoral and cellular immune factors contributing to protection against Campylobacter illness in humans. Based on these results, which confirmed earlier clinical trial results, Antex and SmithKline Beecham plan to continue the commercial development of the vaccine to address the optimal formulations, dosing regimen, and protection in field trials."
Vaccine Produces Immune Response
This double-blinded, placebo-controlled Phase II challenge study evaluated the clinical and immunological outcomes of the oral vaccine in healthy adult volunteers against experimental infection with Campylobacter. The sequence of clinical and microbiological events associated with Campylobacter infections was characterized and correlated with immune response patterns in vaccinated, previously infected and control volunteers.
The trial was conducted in two stages. In the first stage, 28 individuals were given various concentrations of live organisms to determine the amount required to establish a stringent model of experimental infection and cause illness in at least 70% of the volunteers. Illness was measured by the occurrence, time of onset, and duration of signs and symptoms including diarrhea, fever, and enteritis. The results from the first stage established that approximately 109 live Campylobacter bacteria given orally produced the required level of experimental illness.
Additionally, the immune response to the Campylobacter infection was measured. The results showed that Campylobacter infection induced a number of bacteria-specific humoral and cell-mediated immune responses, including an interferon-gamma (INF-g) response, as well as local intestinal and systemic antibody production. INF-g production typifies a Th1-type
T-cell response, which is predominantly indicative of active cell-mediated immunity; while anti- Campylobacter antibody responses in the intestine and blood are more typically markers of active mucosal and more generalized humoral immunity.
The second stage of the study consisted of 40 individuals, 32 who received two oral doses (two weeks apart) of either a placebo (13) or the Campylobacter vaccine (19) and 8 of the previously infected volunteers from stage one. Approximately four weeks after administration of either the placebo, vaccine or first infection, all volunteers were fed a suspension containing 109 live Campylobacter bacteria.
The results of this Phase II trial with respect to safety were similar to the Phase I studies, in that there were no serious adverse events related to vaccination. As anticipated, some of the volunteers (approximately 25%) experienced a mild gastrointestinal reaction (3 or more loose stools) in the one to two days following the first oral vaccination. This mild reaction did not cause any complications for the volunteers and did not impact on their normal daily activities.
Possible modifications of the adjuvant component in the vaccine formulation will be addressed in the future trials.
Protection Correlated with Immune Response
The results of this trial also confirmed the Phase I clinical studies with respect to the immunogenicity of the vaccine. Like live infection, the vaccine induced Campylobacter-specific humoral and cellular immune responses in the majority of the recipients. Eighty six percent (86%) of the vaccinees exhibited vaccine-specific INF-g responses and 58-63% had vaccine-specific IgA or IgG antibody secreting cells in their blood post-vaccination. Most importantly, new immunological observations were made during the course of this Phase II trial that showed that vaccine-specific INF-g responses, along with the production of local intestinal IgA antibodies directed against Campylobacter, were the strongest immune correlates of protection.
Seventy one percent (71%) of the volunteers protected against illness had increased INF-g and intestinal IgA antibody responses, in contrast to only 28% and 24%, respectively, of the unprotected individuals (those exhibiting clinical symptoms of diarrhea, fever and enteritis). The previously infected volunteers were protected from challenge and showed immunological responses similar to the other protected volunteers. While the level of protection against challenge in the vaccinated group was not as apparent when compared to the previously infected group, it is expected that a change in the dosage schedule will enhance the effectiveness of the vaccine in future clinical trials.
Dr. Esposito continued, "This trial enabled us to identify potential immune correlates of protection from an experimental model of Campylobacter infection in humans and encourages us to continue the development of our vaccine. The results are consistent with earlier preclinical research, where we showed that increases in INF-g and intestinal antibody production were associated with protection from infection in animal models. In future clinical trials we will further optimize the formulation and delivery of the oral Campylobacter vaccine, and ultimately evaluate the vaccine's ability to protect against Campylobacter illness in a high-risk, natural field setting."
Antex's Campylobacter vaccine is based on the patented NST (Nutriment Signal Transduction) technology. NST is a highly innovative and proprietary platform for the development of products to prevent and treat a range of bacterial infections.
The trial was conducted at the U.S. Army Medical Research Institute of Infectious Diseases in Maryland by the U.S. Navy and Army, and was a continuation of ongoing research under existing Cooperative Research and Development Agreements between the Navy and Antex and between the Navy and SmithKline Beecham. This research was also supported by the U.S. Army Medical Materiel Development Activity, U.S. Army Medical Research and Materiel Development Command.
Clinical Development to Continue
"Our enthusiasm for proceeding with future clinical trials of this vaccine is based on these promising results and other prior preclinical and Phase I human studies," said Dr. Larry R. Ellingsworth, Vice President of Research and Development of Antex. Dr. Ellingsworth continued, "We now have the immunological tools needed to help accelerate the further development and evaluation of this highly innovative vaccine concept." He added, "The rapid progress of this project has clearly demonstrated the benefits that can accrue from the Department of Defense and industry partnerships to solve common medical problems."
Two prior Phase I safety and immunogenicity clinical trials have been successfully completed; the first assessed dose-ranges of orally administered inactivated Campylobacter whole cells given alone and the second tested dose-ranges of the inactivated whole cells given in combination with an adjuvant, the oral vaccine formulation evaluated in this Phase II study.
The data from both Phase I trials showed that the vaccine is safe and immunogenic and that the adjuvant both improved and broadened the nature of the immune responses elicited by the vaccine. Volunteers responded to the vaccine in a dose-dependent manner, including the appearance of anti-Campylobacter intestinal IgA-antibody production and the induction of vaccine-specific INF-g responses. These data are consistent with results of preclinical safety and immunogenicity studies in animal models. Data from animal models also showed that the vaccine provides protective immunity against live infections and illness.
Over 2.5 million cases of Campylobacter diarrhea are estimated to occur in the U.S. annually, with outbreaks and sporadic cases of Campylobacter gastroenteritis and diarrhea occurring frequently among military personnel stationed in the U.S. and overseas. Diarrheal diseases are considered a major cause of death globally, and 400-500 million cases of Campylobacter diarrhea occur throughout the world each year. Campylobacter infection is also considered to cause one of the most severe forms of traveler's diarrhea among visitors to less developed countries. In addition, this bacterium tends to show the highest frequency of multiple antibiotic resistance compared to other bacterial pathogens contributing to this syndrome in travelers.
Antex Biologics Inc. is a biopharmaceutical company committed to improving human health by developing new products to prevent and treat infectious diseases and related disorders. The company has two other vaccines in clinical development; one is for Helicobacter pylori, the other is directed against Haemophilus influenzae. The company's common stock is quoted on the NASDAQ OTC Bulletin Board under the ticker symbol ANTX.
SmithKline Beecham (NYSE:SBH) - one of the world's leading healthcare companies - discovers, develops, manufactures, and markets pharmaceuticals, vaccines, over-the-counter medicines, and health-related consumer products, and provides healthcare services including clinical laboratory testing, disease management, and pharmaceutical benefit management.
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