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

This study has been completed.
Sponsor:
Collaborator:
Institut National de la Santé Et de la Recherche Médicale, France
Information provided by (Responsible Party):
University Hospital, Lille
ClinicalTrials.gov Identifier:
NCT01512277
First received: January 9, 2012
Last updated: August 26, 2013
Last verified: August 2013
  Purpose

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


Condition Intervention Phase
Schistosomiasis
Bilharziasis
Urinary Schistosomiasis
Biological: rSh28GST
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Phase 1 Study Evaluating Safety and Immunological Criteria of Efficacy of the Recombinant Vaccine Candidate Bilhvax Against Schistosomiasis

Resource links provided by NLM:


Further study details as provided by University Hospital, Lille:

Primary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: D1 : administration, clinical observation, clinical analysis ] [ Designated as safety issue: Yes ]
    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

  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: D21 : clinical observation, clinical analysis ] [ Designated as safety issue: Yes ]
    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

  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: D28 : administration, clinical observation, clinical analysis ] [ Designated as safety issue: Yes ]
    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

  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: D29 : clinical observation, clinical analysis ] [ Designated as safety issue: Yes ]
    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

  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: D120 : clinical observation, clinical analysis ] [ Designated as safety issue: Yes ]
    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

  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: D150 : administration, clinical observation, clinical analysis ] [ Designated as safety issue: Yes ]
    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

  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: D165 : clinical observation, clinical analysis ] [ Designated as safety issue: Yes ]
    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

  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: D180 : clinical observation, clinical analysis ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • Immunogenicity [ Time Frame: Day of first administration and D21, D28, D29, D49, D120, D150, D165 and D180 ] [ Designated as safety issue: No ]
    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.


Enrollment: 24
Study Start Date: September 1998
Study Completion Date: September 1999
Primary Completion Date: March 1999 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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

Ages Eligible for Study:   18 Years to 30 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01512277

Locations
France
Centre d'Investigation Clinique - CHRU de Lille
Lille, France, 59000
Sponsors and Collaborators
University Hospital, Lille
Institut National de la Santé Et de la Recherche Médicale, France
Investigators
Principal Investigator: André CAPRON, MD Institut National de la Santé Et de la Recherche Médicale, France
Study Director: Gilles RIVEAU, PhD Institut National de la Santé Et de la Recherche Médicale, France
Study Chair: Christian LIBERSA, MD CIC, University Hospital, Lille
  More Information

Publications:
Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT01512277     History of Changes
Other Study ID Numbers: CP97/104, 98002, 980056
Study First Received: January 9, 2012
Last Updated: August 26, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Lille:
vaccines
safety
drug tolerance
immunogenic protein
antibody response
cytokine

Additional relevant MeSH terms:
Schistosomiasis
Schistosomiasis haematobia
Trematode Infections
Helminthiasis
Parasitic Diseases
Urinary Tract Infections
Infection
Urologic Diseases

ClinicalTrials.gov processed this record on April 14, 2014