Study of Safety and Immune Response of the Sm14 Vaccine in Adults of Endemic Regions

NCT03041766 | Completed Phase 2 DMC

• 1 other identifier: Sm14-2a-Sn
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The clinical trial phase 2a is designed to assess the safety of the active ingredient (protein + adjuvant) and secondarily its immunogenicity in healthy male adults from 18 to 49 years of age with a history of infection with intestinal and urinary schistosomiasis, living in the Valley of the Senegal River, a highly endemic area for schistosomiasis. Two arms in the study will test different doses of GLA-SE adjuvant (2.5 and 5 μg). This phase IIA in adults is considered to be a preliminary step in safety before starting trials in children in endemic areas to S. mansoni or S. haematobium, target population of the vaccine.

Conditions

Schistosomiasis

Keywords

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

Outcome Measures

Primary Outcomes (5)

• 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).

  within 7 days of the administration of the first dose

• 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).

  D30-D37: within 7 days of the administration of the second dose

• 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).

  D60-67 : within 7 days of the administration of the third dose

• 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. Laboratory tests (blood count, liver and kidney biological functions).

  D90 : three months after the first injection

• 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. Laboratory tests (blood count, liver and kidney biological functions).

  D120 : four months after the first injection

Secondary Outcomes (5)

• Qualitative and quantitative assessment of the Immunogenicity

  Day of first administration

• Qualitative and quantitative assessment of the Immunogenicity

  30 days after the first administration

• Qualitative and quantitative assessment of the Immunogenicity

  60 days after the first administration

• Qualitative and quantitative assessment of the Immunogenicity

  90 days after the first administration

• Qualitative and quantitative assessment of the Immunogenicity

  120 days after the first administration

Study Arms (2)

Group 1

EXPERIMENTAL

Adults with an infectious history of S. haematobium and S. mansoni and pretreated with 1 dose of Praziquantel (3 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 2

EXPERIMENTAL

Adults with an infectious history of S. haematobium and S. mansoni and pretreated with 1 dose of Praziquantel (3 weeks prior to the first vaccine injection) receiving three (3) intramuscular injections of 50 μg Sm14 with 5.0 μg GLA-SE solution at D0, W4, W8 (D=day; W=week). Three-month follow-up (W12, W20).

Biological: Sm14; Drug: GLA-SE solution

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

Two (2) adjuvant concentrations will be made and packaged at 0.4 mL/vial, per GMP standards. One lot at the concentration of 10µg/mL for injection in the first cohort at 2.5µg GLA-SE/injection and one lot at the concentration of 20µg/mL for the second cohort intended to receive 5.0µg of 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: 18 Years - 49 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Living in one of selected villages in Saint-Louis Region (Senegal).
• Free of obvious/severe health problems except schistosomiasis, as established by clinical examination and blood analysis, i.e. hematological exams, liver and renal function tests.
• Written informed consent to participate obtained
• Residence in the area during the period of the study.

You may not qualify if:

• 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
• Acute disease at time of enrollment.
• Other conditions which in opinion of the PI may potentially represent a danger for the patient to be enrolled.
• Non residence in the study area or intent to move during the study period

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 (5)

• 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

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

• Doudou 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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: November 16, 2016
• First Posted: February 3, 2017
• Study Start: December 6, 2016
• Primary Completion: April 6, 2017
• Study Completion: June 2, 2017
• Last Updated: December 14, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)