Safety/Efficacy Trial of Killed Leishmania Vaccine in Volunteers With no Response to Leishmanin

This study has been completed.
Sponsor:
Collaborators:
Pasteur Institute of Iran, Tehran, Iran
Razi Vaccine & Serum Institute, Iran
Centre for Disease Control & Management, Ministry of Health & Medical Education
Information provided by:
Tehran University of Medical Sciences
ClinicalTrials.gov Identifier:
NCT00429715
First received: January 31, 2007
Last updated: February 16, 2011
Last verified: February 2011
  Purpose

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 no response to leishmanin will be injected twice (30 days apart) with Alum-ALM 200 ug + 1/10 of BCG (n = 50) or BCG (n = 50) or BCG 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.


Condition Intervention Phase
Healthy
Biological: Alum-ALM + BCG
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
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 no Response to Leishmanin

Resource links provided by NLM:


Further study details as provided by Tehran University of Medical Sciences:

Primary Outcome Measures:
  • Occurrence of local and/or systemic adverse events (AEs) within 30 days after vaccination assessed by interview, physical examination.
  • Percentage of volunteers protected against CL (absence of a lesion) compared to controls at day 180 + 15 after LZ.

Secondary Outcome Measures:
  • Percentage of volunteers partially protected against CL compared to controls at day 180 + 15 post LZ.
  • To assess the safety, non expected adverse events after leishmanization, assessed by interview and physical examination (local reactions at the injection site and systemic side effects) until the lesions are completely healed.
  • In vivo test: Leishmanin skin tests (LST) prior to vaccination (baseline), at Day 23-28 after first injection and at day 52-58 and (before leishmanization) to assess the

Estimated Enrollment: 150
Study Start Date: January 2007
Study Completion Date: December 2007
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alum-ALM + BCG
Alum-ALM + BCG
Biological: Alum-ALM + BCG
Alum precipitated autoclaved L. major
Other Name: Alum precipitated autoclaved L. major
Biological: Alum-ALM + BCG
Arm 1=Alum-ALM + BCG Arm 2=BCG Arm 3=Placebo comparator
Biological: Alum-ALM + BCG
Alum-ALM + BCG
Active Comparator: BCG
BCG
Biological: Alum-ALM + BCG
Alum precipitated autoclaved L. major
Other Name: Alum precipitated autoclaved L. major
Biological: Alum-ALM + BCG
Arm 1=Alum-ALM + BCG Arm 2=BCG Arm 3=Placebo comparator
Biological: Alum-ALM + BCG
Alum-ALM + BCG
Placebo Comparator: BCG diluent
Diluent
Biological: Alum-ALM + BCG
Alum precipitated autoclaved L. major
Other Name: Alum precipitated autoclaved L. major
Biological: Alum-ALM + BCG
Arm 1=Alum-ALM + BCG Arm 2=BCG Arm 3=Placebo comparator
Biological: Alum-ALM + BCG
Alum-ALM + BCG

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   16 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men or women age between 16 to 60 years.
  • Generally in good health.
  • No known immunological deficiency, including HIV infection (by medical history).
  • No fever at the time of vaccination i.e. oral body temperature <37.5°C.
  • No history/suspicion/presence of kala-azar or cutaneous leishmaniasis (CL).
  • No history of leishmanization.
  • No history of vaccination against leishmaniasis.
  • No involvement in other drug or vaccine trial(s) during the study period.
  • No other known or planned vaccination within 1 month prior to the study and during the study period.
  • No current or foreseeable use of immunosuppressors (i.e. corticosteroids) within one month prior to the vaccination and during the period of the study.
  • No known allergy to a vaccine component (e.g. BCG, alum hydroxide, etc.).
  • Written informed consent provided. If the volunteer is under 18 years old, the legal guardian's signature is required on the informed consent.

Exclusion Criteria:

  • Pregnancy.
  • Women should not be pregnant and/or lactating and/or planning pregnancy throughout the study period until complete healing of the lesion induced by vaccination and/or leishmanization. A urinary pregnancy test will be performed for all women of child bearing potential at entry and adequate contraception throughout the study should be used if applicable.
  • Evidence of prior CL or leishmaniasis (e.g. sign of scar resembling leishmaniasis, confirmed by physical examination).
  • Evidence of serious diseases, allergy or allergic conditions leading to medical consultation and treatment especially with steroids or levamisole, recent surgery or hospitalisation, according to the physical examination and medical history interview.
  • Presence of any chronic illness/disease including diabetes mellitus, tuberculosis, leprosy, epilepsy and hypertension.
  • Abnormal haematology and clinical chemistry (See Sections 8.1.2.1 and 8.1.2.2 for normal ranges of laboratory values).
  • Presence of fever at the time of vaccination, i.e. body temperature (by mouth) > 37.5 °C.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00429715

Locations
Iran, Islamic Republic of
Center for Research & Training in Skin Diseases & Leprosy, TUMS
Tehran, 14166, Iran, Islamic Republic of
Sponsors and Collaborators
Tehran University of Medical Sciences
Pasteur Institute of Iran, Tehran, Iran
Razi Vaccine & Serum Institute, Iran
Centre for Disease Control & Management, Ministry of Health & Medical Education
Investigators
Principal Investigator: Ali Khamesipour Center for Research & Training in Skin Diseases & Leprosy, Tehran University of Medical Sciences
Study Chair: Farrokh Modabber Center for Research & Training in Skin Diseases & Leprosy, Tehran University of Medical Sciences
  More Information

Publications:
1. Lancet 1987; (1): 401-405. 2. New Generation Vaccines, Levine M et al. Eds. Dekker, New York. Chapter 82, 2004. 3. Int J Dermatol. 2002; 41: 73-8. 4. Clinics in Dermat. 14, 5: 489-495, 1996. 5. Clinics in Dermat. 14, 5: 496-502, 1996. 6. The Lancet, 351, 9115:1540-3, 1998. 7. Vaccine, 17, 5: 466-72,1999. 8. Lancet, 356: 1565-69, 2000. 9. Vaccine 2002; 21:174-80 10. J Immunol., 163, 8: 4481-8, 1999. 11. Vaccine, 19: 3485-92, 2001 12. Trans. Roy. Soc. Trop. Med. & Hyg. 97:365-368, 2003 13. J. Exp. Immunol. 2005 (In press). 14. The history of leishmaniasis. Gilles HM, ed. In: Handbook of protozoal infections., Chapman and Hall, 2000. 15. "New developments with human and veterinary vaccine". A Mizrahi, I Hertman, MA Klingberg, A Kohn, eds., Vol. 47, pp. 259-285, Alan R Liss Inc, New York, 1980. 16. Research on Strategies for the Control of Leishmaniasis. Walton, B, Wijeyaretne, PM, Modabber, F. (Eds), International Development Research Center, Ottawa, 336-369, 1988. 17. Bull Soc Fran parasit, 10:183, 1992. 18. Iranian J. Med. Sciences 23, 3&4: 74-80, 1998. 19. Vaccine 23:3642-8, 2005. 20. N Engl J Med. 293,10: 501-2, 1975.

Responsible Party: Ali Khamesipour, Associate Professor, Center for Research & Training in Skin Diseases & Leprosy
ClinicalTrials.gov Identifier: NCT00429715     History of Changes
Other Study ID Numbers: CT110-1384, J/423/1057, 30/05/1385
Study First Received: January 31, 2007
Last Updated: February 16, 2011
Health Authority: Iran: Ministry of Health

Keywords provided by Tehran University of Medical Sciences:
Leishmaniasis vaccine
Alum-ALM
First generation vaccine
Healthy volunteers
No response to leishmanin
No history of cutaneous leishmaniasis

Additional relevant MeSH terms:
Aluminum sulfate
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014