Clinical Trial of Bilhvax,a Vaccine Candidate Against Schistosomiasis

Schistosomiasis Clinical Trial

— Bilhvax1a  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01512277
• Other study ID #: CP97/104
• Secondary ID: 98002980056
• Status: Completed
• Phase: Phase 1
• First received: January 9, 2012
• Last updated: August 26, 2013
• Start date: September 1998
• Est. completion date: September 1999

Study information

• Verified date: August 2013
• Source: University Hospital, Lille
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: September 1999
• Est. primary completion date: March 1999
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 30 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Bilharziasis
• Schistosomiasis
• Schistosomiasis haematobia
• Urinary Schistosomiasis

Intervention

Biological:
• rSh28GST
subcutaneous route at Day 0, Day 28, and Day 150 for the third administration of 100µg for Arm 1

Locations

Country	Name	City	State
France	Centre d'Investigation Clinique - CHRU de Lille	Lille

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Lille	Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

References & Publications (4)

Capron A, Capron M, Riveau G. Vaccine development against schistosomiasis from concepts to clinical trials. Br Med Bull. 2002;62:139-48. Review. — View 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. Review. — View 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. Review. — View Citation

Riveau G, Deplanque D, Remoué 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Secondary	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	No