Clinical Trial of Bilhvax,a Vaccine Candidate Against Schistosomiasis

NCT ID: NCT01512277

Last Updated: 2013-08-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

1998-09-30

Study Completion Date

1999-09-30

Brief Summary

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The purpose of this clinical study is to evaluate safety and immunogenicity in adult healthy volunteers of the vaccine candidate against schistosomiasis named Bilhvax.

Detailed Description

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The development of an efficient vaccine against human schistosomiasis represents a major challenge for the improvement of health in many developing countries.

Schistosomiasis affects millions people in numerous countries and hampers economical development of tropical areas.

Although progress has been made for the limitation of the disease severity by chemotherapy, continuous re-infection and risks of drug resistance point to the necessary development of alternative strategies.

It is widely agreed that immunological prevention of chronic parasitic infections will be extremely difficult to achieve. Conversely in some major helminth infections like schistosomiasis, where parasite eggs laying in the tissues is the exclusive cause of pathology and the elimination of eggs in nature is the source of transmission, inhibition of parasite fecundity might represent for the future a novel way to prevent the deleterious effects of these chronic infections in man.

The concept to target by vaccination the cause of the pathology rather than the parasite itself would provide a potent tool to control a major chronic infection.

After years of basic studies on effector and regulatory mechanisms of immune response against schistosomiasis it has been identify a schistosome molecule named glutathione S-transferase 28 kDa (28GST) presenting a potential as vaccine candidate.

This 28GST have been cloned and named Bilhvax. It has been shown that immunization with such schistosome GST would dramatically decrease female worm fecundity and egg viability in various hosts. It was demonstrated that these anti-fecundity effects are associated with the production of antibodies neutralizing the GST enzymatic activities obtained through a Th2-type immune response. This correlation between anti-fecundity effects and inhibition-mediated antibodies demonstrated in several animal models was re-enforced by epidemiological studies showing that such acquired antibodies produced during infection could be detected in adult individuals naturally resistant to the re-infection.

The present phase 1 clinical trial is conducted in healthy Caucasian volunteers to evaluate as primary endpoint the safety of the recombinant Sh28GST (rSh28GST) in Alum (named Bilhvax), a vaccine candidate against human urinary schistosomiasis. The secondary endpoint is to evaluate immunogenicity of Bilhvax, to determine the profile of the immune response, and to estimate the neutralizing capacity of the antibodies against the rSh28GST enzymatic activity.

The recombinant S. haematobium 28GST expressed in yeast is produced by Eurogentec SA in GMP conditions.

Conditions

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Schistosomiasis Bilharziasis Urinary Schistosomiasis

Keywords

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vaccines safety drug tolerance immunogenic protein antibody response cytokine

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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3 administrations of 100 µg of rSh28GST

Adult volunteers (n=8) receive 100μg of rSh28GST together with aluminium hydroxide (Alum) as adjuvant at D0, D28, and D150.

Group Type EXPERIMENTAL

rSh28GST

Intervention Type BIOLOGICAL

subcutaneous route at Day 0, Day 28, and Day 150 for the third administration of 100µg for Arm 1

2 administrations of 300 µg of rSh28GST

Adult volunteers (n=8) receive 300μg of rSh28GST together with aluminium hydroxide (Alum) as adjuvant at D0 and D28.

Group Type EXPERIMENTAL

rSh28GST

Intervention Type BIOLOGICAL

subcutaneous route at Day 0, Day 28, and Day 150 for the third administration of 100µg for Arm 1

Placebo

Adult volunteers (n=8) receive aluminium hydroxide (Alum) alone at D0 and D28.

Group Type PLACEBO_COMPARATOR

rSh28GST

Intervention Type BIOLOGICAL

subcutaneous route at Day 0, Day 28, and Day 150 for the third administration of 100µg for Arm 1

Interventions

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rSh28GST

subcutaneous route at Day 0, Day 28, and Day 150 for the third administration of 100µg for Arm 1

Intervention Type BIOLOGICAL

Other Intervention Names

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Bilhvax

Eligibility Criteria

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Inclusion Criteria

* Caucasian volunteers
* No smoker
* biological parameters (haematological, biochemical, renal and hepatic) in normal range
* Health Insurance
* sign inform consent

Exclusion Criteria

* inflammatory or immunological pathology such as atopic diseases, evidence of inflammation or acute infection (including positive serology to viral hepatitis B and C or HIV)
* any immunological deficiency
* any clinically relevant alcohol or drug use (cannabis, opiates, cocaine, amphetamines, benzodiazepines, nicotine, barbiturates, meprobamate or antidepressant drugs according to urine drug and metabolites screen)
* current immunosuppressor treatment
* any other medication use within 2 weeks before the study
* any vaccination within the last 6 months
* no antibodies against Sh28GST protein.
Minimum Eligible Age

18 Years

Maximum Eligible Age

30 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role collaborator

University Hospital, Lille

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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André CAPRON, MD

Role: PRINCIPAL_INVESTIGATOR

Institut National de la Santé Et de la Recherche Médicale, France

Gilles RIVEAU, PhD

Role: STUDY_DIRECTOR

Institut National de la Santé Et de la Recherche Médicale, France

Christian LIBERSA, MD

Role: STUDY_CHAIR

CIC, University Hospital, Lille

Locations

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Centre d'Investigation Clinique - CHRU de Lille

Lille, , France

Site Status

Countries

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France

References

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Capron A, Riveau G, Capron M, Trottein F. Schistosomes: the road from host-parasite interactions to vaccines in clinical trials. Trends Parasitol. 2005 Mar;21(3):143-9. doi: 10.1016/j.pt.2005.01.003.

Reference Type BACKGROUND
PMID: 15734662 (View on PubMed)

Capron A, Riveau GJ, Bartley PB, McManus DP. Prospects for a schistosome vaccine. Curr Drug Targets Immune Endocr Metabol Disord. 2002 Oct;2(3):281-90. doi: 10.2174/1568008023340587.

Reference Type BACKGROUND
PMID: 12476492 (View on PubMed)

Capron A, Capron M, Riveau G. Vaccine development against schistosomiasis from concepts to clinical trials. Br Med Bull. 2002;62:139-48. doi: 10.1093/bmb/62.1.139.

Reference Type BACKGROUND
PMID: 12176856 (View on PubMed)

Riveau G, Deplanque D, Remoue F, Schacht AM, Vodougnon H, Capron M, Thiry M, Martial J, Libersa C, Capron A. Safety and immunogenicity of rSh28GST antigen in humans: phase 1 randomized clinical study of a vaccine candidate against urinary schistosomiasis. PLoS Negl Trop Dis. 2012;6(7):e1704. doi: 10.1371/journal.pntd.0001704. Epub 2012 Jul 3.

Reference Type RESULT
PMID: 22802974 (View on PubMed)

Other Identifiers

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98002

Identifier Type: OTHER

Identifier Source: secondary_id

980056

Identifier Type: OTHER

Identifier Source: secondary_id

CP97/104

Identifier Type: -

Identifier Source: org_study_id