Safety/Efficacy Trial of Killed Leishmania Vaccine in Volunteers With Positive Response to Leishmanin (LST>0)
Development of a safe and effective vaccine against leishmaniasis started more than 10 years ago under WHO/TDR supervision. An autoclaved L. major vaccine (ALM) mixed with BCG has been tested in human in Iran, Pakistan and Sudan. Long term follow up of the vaccinees showed no untoward reactions except the skin reaction at the site of injection. The efficacy results of ALM was not satisfactory. In order to enhance immunogenicity of the vaccine, ALM was adsorbed to alum (Aluminum hydroxide). Alum-ALM plus adjuvant showed to induce protection in Rhesus monkeys against cutaneous leishmaniasis and in Languor monkeys against visceral leishmaniasis. Two trials of a single injection of different doses of Alum-ALM mixed with 1/10th of normal dose of BCG was carried out in healthy volunteers from a non endemic area of Sudan. The safety/immunogenicity parameters of the volunteers were closely monitored and the results showed that side effects were minimal and confined to the site of injection in the form of mild local pain, induration and ulceration, all associated with BCG vaccination. The immunogenicity results showed the strongest immune response seen in any Leishmania vaccine trials so far. It seems that this new formulation is an appropriate candidate for further development. Inoculation with live virulent Leishmania to produce a lesion for the purpose of preventing natural infection is known as leishmanization. The induced lesion heals and the person is usually protected against further infections. This method of prevention was practiced for centuries in the region. In this study volunteers with response to leishmanin will be injected twice (30 days apart) with Alum-ALM 200 ug + 1/10 of BCG (n = 50) or diluent alone (n = 50) as control. All volunteers will be leishmanized on day 60 post vaccination. In this trial, volunteers are protected either by vaccine or by leishmanization. The leishmanized volunteers will be visited by weekly and the development and healing process of the lesion will be monitored until complete healing of every volunteer. The immune responses of the volunteers will be evaluated. Vaccine efficacy is defined by the percent reduction in the number of volunteers developing a lesion following leishmanization as compared to controls on days 240.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||A Randomized, Safety, Immunogenicity & Efficacy Study of Autoclaved Leishmania Major Plus BCG vs. BCG (Double Blind) or Placebo (Open), in Healthy High Risk Iranian Volunteers With Positive Response to Leishmanin (LST>0)|
- Occurrence of local/systemic adverse events after vaccination assessed by
- interview, physical examination in volunteers with a response to
- Leishmanin (LST>0);
- Percentage of the volunteers with LST>0 protected against CL
- (absence of a lesion).
- Percentage of volunteers partially protected against CL compared to controls at day 240.
- To assess immune response of the volunteers at baseline (prior to vaccination), before leishmanization to evaluate the immunogenicity of the vaccine.
|Study Start Date:||January 2007|
|Study Completion Date:||December 2007|
|Primary Completion Date:||September 2007 (Final data collection date for primary outcome measure)|
No Intervention: Alum-ALM + BCG
Alum-ALM + BCG
No Intervention: Placebo
Biological: Alum-ALM + BCG
Alum-ALM + BCG 200 ug per injection
Other Name: Alum pericipitated autoclaved L. major
|Iran, Islamic Republic of|
|Center for Research & Training in Skin Diseases & Leprosy|
|Tehran, Iran, Islamic Republic of, 14166|
|Principal Investigator:||Ali Khamesipour||Center for Research and Training in Skin Disease and Leprosy,|