Clinical trial NCT01512277: Clinical Trial of Bilhvax,a Vaccine Candidate Against Schistosomiasis
Official title: Phase 1 Study Evaluating Safety and Immunological Criteria of Efficacy of the Recombinant Vaccine Candidate Bilhvax Against Schistosomiasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Schistosomiasis
Bilharziasis
Urinary Schistosomiasis
Keywords: vaccines
safety
drug tolerance
immunogenic protein
antibody response
cytokine
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2012-01-19
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: All subjects had to meet the study inclusion criteria within 21 days prior to treatment,

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.

Primary outcomes:
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: D1 : administration, clinical observation, clinical analysis
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: D21 : clinical observation, clinical analysis
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: D28 : administration, clinical observation, clinical analysis
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: D29 : clinical observation, clinical analysis
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: D120 : clinical observation, clinical analysis
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: D150 : administration, clinical observation, clinical analysis
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: D165 : clinical observation, clinical analysis
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: D180 : clinical observation, clinical analysis
Secondary outcomes:
measure: Immunogenicity
timeFrame: Day of first administration and D21, D28, D29, D49, D120, D150, D165 and D180
Other outcomes:
Locations:
city: Lille
country: France
facility: Centre d'Investigation Clinique - CHRU de Lille
Study officials:
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: André CAPRON, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: Gilles RIVEAU, PhD
role: STUDY_DIRECTOR
affiliation: CIC, University Hospital, Lille
name: Christian LIBERSA, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.