Clinical Trial of Bilhvax,a Vaccine Candidate Against Schistosomiasis (Bilhvax1a)

Phase 1 Study Evaluating Safety and Immunological Criteria of Efficacy of the Recombinant Vaccine Candidate Bilhvax Against Schistosomiasis

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

Study Overview

• Status: Completed
• Conditions: Schistosomiasis; Urinary Schistosomiasis; Bilharziasis
• Intervention / Treatment: Biological: rSh28GST

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Lille, France, 59000
    • Centre d'Investigation Clinique - CHRU de Lille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: rSh28GST; subcutaneous route at Day 0, Day 28, and Day 150 for the third administration of 100µg for Arm 1; Other Names: Bilhvax
Experimental: 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.	Biological: rSh28GST; subcutaneous route at Day 0, Day 28, and Day 150 for the third administration of 100µg for Arm 1; Other Names: Bilhvax
Placebo Comparator: Placebo; Adult volunteers (n=8) receive aluminium hydroxide (Alum) alone at D0 and D28.	Biological: rSh28GST; subcutaneous route at Day 0, Day 28, and Day 150 for the third administration of 100µg for Arm 1; Other Names: Bilhvax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection. Complete physical examination including an examination of general appearance, body weight and rectal temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances	D1 : administration, clinical observation, clinical analysis
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection. Complete physical examination including an examination of general appearance, body weight and rectal temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances	D21 : clinical observation, clinical analysis
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection. Complete physical examination including an examination of general appearance, body weight and rectal temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances	D28 : administration, clinical observation, clinical analysis
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection. Complete physical examination including an examination of general appearance, body weight and rectal temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances	D29 : clinical observation, clinical analysis
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection. Complete physical examination including an examination of general appearance, body weight and rectal temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances	D120 : clinical observation, clinical analysis
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection. Complete physical examination including an examination of general appearance, body weight and rectal temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances	D150 : administration, clinical observation, clinical analysis
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection. Complete physical examination including an examination of general appearance, body weight and rectal temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances	D165 : clinical observation, clinical analysis
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection. Complete physical examination including an examination of general appearance, body weight and rectal temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances	D180 : clinical observation, clinical analysis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity	Immunogenicity was evaluated by dosage of specific antibody production, capacity of sera to inhibit enzymatic activity of the antigen, and immune profile estimation by in vitro cytokines production assay.	Day of first administration and D21, D28, D29, D49, D120, D150, D165 and D180

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Study Director: Gilles RIVEAU, PhD, Institut National de la Santé Et de la Recherche Médicale, France; Principal Investigator: André CAPRON, MD, Institut National de la Santé Et de la Recherche Médicale, France; Study Chair: Christian LIBERSA, MD, CIC, University Hospital, Lille

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 1998
• Primary Completion (Actual): March 1, 1999
• Study Completion (Actual): September 1, 1999

Study Registration Dates

• First Submitted: January 9, 2012
• First Submitted That Met QC Criteria: January 13, 2012
• First Posted (Estimate): January 19, 2012

Study Record Updates

• Last Update Posted (Estimate): August 27, 2013
• Last Update Submitted That Met QC Criteria: August 26, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: safety; cytokine; antibody response; vaccines; drug tolerance; immunogenic protein
• Additional Relevant MeSH Terms: Infections; Urologic Diseases; Vector Borne Diseases; Parasitic Diseases; Helminthiasis; Urinary Tract Infections; Trematode Infections; Schistosomiasis; Schistosomiasis haematobia
• Other Study ID Numbers: CP97/104; 98002 (Other Identifier: Sponsor); 980056 (DGS)