NCT00429715

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
150

participants targeted

Target at P50-P75 for phase_2 healthy

Timeline
Completed

Started Jan 2007

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2007

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

January 31, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 1, 2007

Completed
3 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2007

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2007

Completed
Last Updated

February 17, 2011

Status Verified

February 1, 2011

Enrollment Period

4 months

First QC Date

January 31, 2007

Last Update Submit

February 16, 2011

Conditions

Healthy

Keywords

Leishmaniasis vaccineAlum-ALMFirst generation vaccineHealthy volunteersNo response to leishmaninNo history of cutaneous leishmaniasis

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (3)

  • 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

Study Arms (3)

Alum-ALM + BCG

EXPERIMENTAL

Alum-ALM + BCG

Biological: Alum-ALM + BCG

BCG

ACTIVE COMPARATOR

BCG

Biological: Alum-ALM + BCG

BCG diluent

PLACEBO COMPARATOR

Diluent

Biological: Alum-ALM + BCG

Interventions

Alum-ALM + BCGBIOLOGICAL

Alum precipitated autoclaved L. major

Also known as: Alum precipitated autoclaved L. major
Alum-ALM + BCGBCGBCG diluent

Eligibility Criteria

Age16 Years - 60 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Center for Research & Training in Skin Diseases & Leprosy, TUMS

Tehran, 14166, Iran

Location

Related Publications (1)

  • 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.

    BACKGROUND

Study Officials

  • Ali Khamesipour

    Center for Research & Training in Skin Diseases & Leprosy, Tehran University of Medical Sciences

    PRINCIPAL INVESTIGATOR

  • Farrokh Modabber

    Center for Research & Training in Skin Diseases & Leprosy, Tehran University of Medical Sciences

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

January 31, 2007

First Posted

February 1, 2007

Study Start

January 1, 2007

Primary Completion

May 1, 2007

Study Completion

December 1, 2007

Last Updated

February 17, 2011

Record last verified: 2011-02

Locations

IR(1)