Anti-Schistosomiasis Vaccine: Sm14 Phase 2b-Sn in School Children

NCT03799510 | Completed Phase 2 DMC

• 1 other identifier: Sm14 Phase 2b - Sn
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

Brief Summary

The clinical trial phase 2b is designed to assess the safety and the specific immune response of the active ingredient (protein + adjuvant) in healthy and then in infected school children from 8 to 11 years of age with intestinal and/or urinary schistosomiasis, living in the Valley of the Senegal River, a highly endemic area for schistosomiasis.

Conditions

Schistosomiasis

Keywords

Schistosomiasis; Recombinant vaccine; rSm14; GLA-SE; Fatty acid-binding protein (FABP); Phase II Clinical Trial; Senegal

Outcome Measures

Primary Outcomes (6)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  Local signs and symptoms included Pain, Swelling and Inflammation at the injection site, heaviness or pain upon passive or active movement of the injected limb, Complete physical examination including an examination of general appearance, body weight and forehead 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.

  within 2 days of the administration of the first dose (Day 0)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  Local signs and symptoms included Pain, Swelling and Inflammation at the injection site, Heaviness or pain upon passive or active movement of the injected limb, Complete physical examination including an examination of general appearance, body weight and forehead 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.

  Day 30-Day 32: within 2 days of the administration of the second dose (Week 4)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  Local signs and symptoms included Pain, Swelling and Inflammation at the injection site. Heaviness or pain upon passive or active movement of the injected limb, Complete physical examination including an examination of general appearance, body weight and forehead 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. Laboratory tests (blood count, liver and kidney biological functions).

  Days 60-67 : within 7 days of the administration of the third dose (Week 8)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  Injection 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 forehead 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.

  Day 90: three months after the first injection (Week 12)

• 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 forehead 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.

  Day 120: four months after the first injection (Week 16)

• 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 forehead 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.

  Day 150: five months after the first injection (Week 21)

Secondary Outcomes (3)

• Qualitative and quantitative assessment of the Immunogenicity

  The Day of first Sm14 vaccine administration (Day 0)

• Qualitative and quantitative assessment of the Immunogenicity

  At the 30th day after the third Sm14 vaccine administration (Week 12)

• Qualitative and quantitative assessment of the Immunogenicity

  At the 90th day after the third Sm14 vaccine administration (Week 21)

Study Arms (3)

Group 1

EXPERIMENTAL

Healthy school children with no infectious history of Schistosomiasis receiving three (3) intramuscular injections of 50 μg Sm14 with 2.5 μg GLA-SE solution at D0, W4, W8 (D=day; W=week). Three-month follow-up (W12, W20).

Biological: Sm14; Drug: GLA-SE solution

Group 2

EXPERIMENTAL

School children with an infectious history of S. haematobium and-or S. mansoni and pretreated with 1 dose of Praziquantel (2-4 weeks prior to the first vaccine injection) receiving three (3) intramuscular injections of 50 μg Sm14 with 2.5 μg GLA-SE solution at D0, W4, W8 (D=day; W=week). Three-month follow-up (W12, W20).

Biological: Sm14; Drug: GLA-SE solution

Group 3

NO INTERVENTION

School children with an infectious history of S. haematobium and S. mansoni and pretreated with 1 dose of Praziquantel (2-4 weeks prior to the first vaccine injection) not receiving vaccine. Control group.

Interventions

Sm14 BIOLOGICAL

Three 0.5 mL intra-muscular injections of the vaccine solution (50μg Sm14) will be administered on D0, W4, W8 (D = day, W = week).

Also known as: rSm14

Group 1; Group 2

GLA-SE solution DRUG

The lot concentration 10μg/mL for injection of 2.5μg GLA-SE/injection.

Also known as: • Glucopyranosyl Lipid A in Stable Emulsion, • Glucopyranosyl Lipid Adjuvant-Stable Emulsion, • Toll-like Receptor 4 Agonist GLA-SE

Group 1; Group 2

Eligibility Criteria

• Age: 8 Years - 11 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Residence in the area during the period of the study.
• Free of obvious/severe health problems except schistosomiasis, as established by clinical examination.
• Written informed consent to participate obtained from subject's parents or legal guardian.
• Free of obvious/severe health problems except schistosomiasis, established by blood analysis, i.e. hematological exams, liver and renal function tests.
• Children of Group 1: not infected, no schistosomiasis history and living in area/village free of Sm and Sh transmission.
• Children Groups 2 \& 3: infected with mansoni or/and haematobium schistosomiasis.

You may not qualify if:

• Child under 20kg of body weight
• Vaccination within 90 days preceding the first dose of Sm14 vaccine candidate, or planned use during the study period.
• Current or previous chronic administration (defined as more than 14 days) of immunosuppressive drugs or other immuno-modifying drugs.
• Known hypersensitivity to any component in the Sm14 vaccine or history of allergic disease.
• Knowledge of non-infectious chronic disease
• Known acute disease.
• Other conditions which in opinion of the PI may potentially represent a danger for the patient to be enrolled.

Sponsors & Collaborators

• Oswaldo Cruz Foundation: lead
• Orygen Biotecnologia SA: collaborator
• Biomedical Research Center EPLS: collaborator
• Access to Advanced Health Institute (AAHI): collaborator

Study Sites (1)

Biomedical Research Center EPLS

Saint-Louis, BP226, Senegal

Location

Related Publications (6)

• Moser D, Tendler M, Griffiths G, Klinkert MQ. A 14-kDa Schistosoma mansoni polypeptide is homologous to a gene family of fatty acid binding proteins. J Biol Chem. 1991 May 5;266(13):8447-54.

  PMID: 2022660 RESULT

• Ramos CR, Spisni A, Oyama S Jr, Sforca ML, Ramos HR, Vilar MM, Alves AC, Figueredo RC, Tendler M, Zanchin NI, Pertinhez TA, Ho PL. Stability improvement of the fatty acid binding protein Sm14 from S. mansoni by Cys replacement: structural and functional characterization of a vaccine candidate. Biochim Biophys Acta. 2009 Apr;1794(4):655-62. doi: 10.1016/j.bbapap.2008.12.010. Epub 2008 Dec 25.

  PMID: 19150418 RESULT

• Coler RN, Bertholet S, Moutaftsi M, Guderian JA, Windish HP, Baldwin SL, Laughlin EM, Duthie MS, Fox CB, Carter D, Friede M, Vedvick TS, Reed SG. Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant. PLoS One. 2011 Jan 26;6(1):e16333. doi: 10.1371/journal.pone.0016333.

  PMID: 21298114 RESULT

• Santini-Oliveira M, Coler RN, Parra J, Veloso V, Jayashankar L, Pinto PM, Ciol MA, Bergquist R, Reed SG, Tendler M. Schistosomiasis vaccine candidate Sm14/GLA-SE: Phase 1 safety and immunogenicity clinical trial in healthy, male adults. Vaccine. 2016 Jan 20;34(4):586-594. doi: 10.1016/j.vaccine.2015.10.027. Epub 2015 Nov 10.

  PMID: 26571311 RESULT

• Lambert SL, Yang CF, Liu Z, Sweetwood R, Zhao J, Cheng L, Jin H, Woo J. Molecular and cellular response profiles induced by the TLR4 agonist-based adjuvant Glucopyranosyl Lipid A. PLoS One. 2012;7(12):e51618. doi: 10.1371/journal.pone.0051618. Epub 2012 Dec 28.

  PMID: 23284726 RESULT

• Tendler M, Almeida MS, Vilar MM, Pinto PM, Limaverde-Sousa G. Current Status of the Sm14/GLA-SE Schistosomiasis Vaccine: Overcoming Barriers and Paradigms towards the First Anti-Parasitic Human(itarian) Vaccine. Trop Med Infect Dis. 2018 Nov 21;3(4):121. doi: 10.3390/tropicalmed3040121.

  PMID: 30469320 RESULT

MeSH Terms

Conditions

Schistosomiasis

Interventions

SM14 protein, Schistosoma mansoni; glucopyranosyl lipid-A

Condition Hierarchy (Ancestors)

Trematode Infections; Helminthiasis; Parasitic Diseases; Infections; Vector Borne Diseases

Study Officials

• Miriam Tendler, MD, PhD

  Oswaldo Cruz Foundation

  STUDY CHAIR

• Modou DIOP, MD

  Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS)

  PRINCIPAL INVESTIGATOR

• Gilles RIVEAU, PharmD, PhD

  Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS).

  STUDY DIRECTOR

• Anne-Marie SCHACHT, CRA

  Biomedical Research Center ESPOIR POUR LA SANTE (BRC-EPLS).

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: No masking
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2019
• First Posted: January 10, 2019
• Study Start: December 13, 2018
• Primary Completion: July 1, 2019
• Study Completion: August 7, 2019
• Last Updated: December 9, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)