Anti-Schistosomiasis Sm14-vaccine in Senegal

• ClinicalTrials.gov Identifier: NCT05658614
• Recruitment Status: Recruiting
• First Posted: December 21, 2022
• Last Update Posted: December 21, 2022
• Sponsor: Oswaldo Cruz Foundation
• Information provided by (Responsible Party): MIRIAM TENDLER, Oswaldo Cruz Foundation

Study Description

Brief Summary:

Previous clinical trials have already demonstrated the safety of the candidate vaccine in adults as well as in children, in good health or infected with schistosomiasis. Regarding the induced immune response, more than 80% of vaccinated subjects were seroconverted after three vaccine injections. The induced immune response was substantial but transient. In order to obtain a more lasting immune response, the investigator will experiment with a new vaccination schedule (2 injections 1-month interval and the 3rd injection 5 months after the first dose), versus the vaccine schedule initially used (3 injections at 1-month interval).

This trial will be the last phase 2 before testing the efficacy of the rSm14 vaccine candidate.

Condition or disease	Intervention/treatment	Phase
Schistosomiasis Mansoni; Schistosomiasis Haematobium; Vaccination; Infection	Biological: Sm14 recombinant vaccine+ GLA-SE adjuvant	Phase 2

Detailed Description:

Adults with a history of infection with S. mansoni and / or S. haematobium, aged 18 to 49 years, pretreated with PZQ before the first vaccine injection (Inclusion) and living in villages in the Saint Louis region where schistosomiasis is endemic.

Comparative test with modification of the vaccine schedule previously used:

• The reference vaccine administration schedule consists of three vaccine administrations one-month interval (Group Vacc3).
• The new vaccine injection schedule will consist of a primary vaccination with two administrations of the vaccine one month apart, then a booster five (5) months after the first injection (Group Vacc2+1). Immunogenicity and safety will be evaluated and compared in these 2 groups.

These two groups of adults will be formed after randomization and pretreatment with PZQ (4 to 8 weeks before their first vaccine administration).

Main objective: to compare the immunological quality of the new vaccination schedule (amplitude and duration) versus the vaccination schedule used in the previous trials, by studying the Sm14 specific antibody response induced both quantitatively and qualitatively. The hypothesis is to obtain a mean response quantitatively higher with the new vaccine schedule.

Secondary objective: safety profile of the two vaccine schedules studied.

Regimen Group Vacc3 (reference group): Adults receiving 3 injections of the vaccine one month apart.

Group Vacc2+1 (experimental group): Adults receiving 2 injections of the vaccine one month apart then a third one five (5) months after the first injection.

Group Vacc3 : subjects will receive three (3) intramuscular injections into the deltoid muscle of 0.5mL of vaccine on Day 0, Week 4 and Week 8.

Group Vacc2+1 : subjects will receive three (3) intramuscular injections into the deltoid muscle of 0.5mL of vaccine on Day 0, Week 4 and Week 20.

Assessment of immunogenicity :

- Comparative Immunoassays between both groups: measures assessing differences in Sm14-specific antibody production several time points after third vaccine injection.

Antibody response evaluated on plasma obtained at:

• Time of the first dose
• 1 month after the third vaccine dose
• 3 months after the third vaccine dose
• 6 months after the third vaccine dose
• 9 months after the third vaccine dose Each subject will have 5 blood samples of 6mL, representing a total volume of 30 mL collected over the duration of the study.
• Cell markers and cytokines production Specific Sm14 cellular response (on PBMC) - production of intracellular cytokines and expression of specific immune markers - will be studied. A measure assessing change between two time points, i.e. time of the first dose and one month after the third injection of vaccine.

Assessment of Safety and Tolerance :

Emerging adverse events defined by an abnormal physical state or physical reaction that did not exist at baseline.

Emerging adverse events defined by abnormal variation in clinical constants. Emerging adverse events defined by abnormal levels of the serum products studied

Physical exams -

Physical exams includes :

Measurement of clinical constants

• Body temperature
• Respiratory rate at rest
• Heart rate at rest
• Blood pressure at rest (systolic + diastolic)

General examination

• Examination of the upper digestive tract (oral level)
• Abdominal examination
• Lung examination

• cardiovascular system examination

  • This will be carried out in the subjects preselected at the pre-inclusion visit, ie 8 days before inclusion.
  • And this will be carried out in subjects included in the clinical trial The physical exams will be carried out before each vaccine injection and followed by an observation at several post injection periods ie 1 hour, 2 hours, 24 hours and 48 hours.

After vaccination (following 3 vaccine injections) subjects will have a physical examination at 1, 3, 6 and 9 months after the third injection.

Thus, during the clinical trial, subjects after inclusion will have 9 medical exams.

Laboratory tests including :

• complete blood cell counts,
• hepatic function : dosage of serum transaminase (liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT))
• renal function : serum creatinine
• serum albumin dosage These analyzes will be performed one week before inclusion (Vpi / W -1) to ensure that the subject is fit to receive the vaccine (satisfactory state of health).

Subsequently, and due to the excellent tolerance observed during previous clinical trials, a biological assessment will only be performed at the request of the investigators.

The villages identified for the clinical trial (n=3 or 4) will be selected approximately 3 months before subject inclusion. Only the adults having an infectious history will be considered for the subject selection.

No PZQ treatment is scheduled during the trial, however, if a person has a spontaneous complaint which is potentially symptomatic for schistosomiasis, parasitological testing will be performed. If the number of Sh eggs reaches 50 eggs / 10mL urine, and / or 400 EPG in stool for Sm, the subject will be treated. If the intensity of the infection is lower, the subject will not be treated but followed up regularly.

With the approval of the coordinator, the Investigator may decide to treat a subject at any time for security reasons.

At the end of the clinical trial, subjects will be tested for schistosomiasis and treated with PZQ if found positive.

Recruitment:

The villages identified for the clinical trial (n=3 or 4) will be selected approximately 3 months before subject inclusion. Only the adults having an infectious history will be considered for the subject selection.

Statistical consideration In terms of immunogenicity, the investigators expect to obtain induction of a significant anti-Sm14 specific immune response (Ab) in at least 70% of subjects (both groups combined). For group Vacc3, the residual average specific immune response one year after the first administration should be comparable to that obtained during phase 2a, ie 50% of the maximal response. For group Vacc2+1, the investigators expect a residual specific immune response at 1 year of 75%. So, an expected improvement in the immune response of 25%. Thus, for a statistical power fixed at 80%, an alpha risk at 5%, the number of subjects required using the Altmann nomogram method is 55 adults for each of the 2 groups.

Predicting a 10% loss to follow-up percentage, 120 subjects will be included in the clinical trial, or 60 subjects per group.

Duration Total duration of the study (32 months): November 2020 to July 2023 (inclusive).

Preparation phase (7-8 months; drafting of documents and submission); clinical trial (17 months (January-February 2022 to June-July 2023); post-trial, immunological analyzes and data management (6-7 months).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

Intervention Model Description

Main objective: to compare the immunological quality of the new vaccination schedule (amplitude and duration) versus the vaccination schedule used in the previous trials, by studying the Sm14 specific antibody response induced both quantitatively and qualitatively. The hypothesis is to obtain a mean response quantitatively higher with the new vaccine schedule.

Secondary objective: safety profile of the two vaccine schedules studied.

• Masking: None (Open Label)
• Masking Description: open label
• Primary Purpose: Prevention
• Official Title: Evaluation of Immunogenicity and Safety of a New Vaccine Schedule Using the Vaccine Candidate Sm14 Against Schistosomiasis in Adults With a History of S. Mansoni and / or S. Haematobium Infection.
• Actual Study Start Date: July 1, 2022
• Estimated Primary Completion Date: September 15, 2023
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Arm 1 (Group Vacc3); Volunteers will receive three (3) intramuscular injections into the deltoid muscle of 0.5mL of of the Sm14+ GLA-SE vaccine on D0, W4 and W8. (D = Day; W = Week). (Vaccination schedule used in previous phases).	Biological: Sm14 recombinant vaccine+ GLA-SE adjuvant; rSm14 - recombinant protein (GMP produced) - 50ug / injection GLA-SE- synthetic Glucopyranosyl lipid A in stable emulsion: 2.5ug / injection
Experimental: Arm 2 (Group Vacc2+1); Volunteers will receive three (3) intramuscular injections of the Sm14+ GLA-SE vaccine into the deltoid muscle of 0.5mL of vaccine on D0, W4 and W20 (new vaccination schedule).	Biological: Sm14 recombinant vaccine+ GLA-SE adjuvant; rSm14 - recombinant protein (GMP produced) - 50ug / injection GLA-SE- synthetic Glucopyranosyl lipid A in stable emulsion: 2.5ug / injection

Outcome Measures

Primary Outcome Measures :

1. assessment of Immunogenicity 1 [ Time Frame: Day 1 ]
   The anti-Sm14 IgG isotypes (Total IgG; IgG1; IgG3; IgG4; IgE) antibody response using an indirect ELISA
2. assessment of Immunogenicity 2 [ Time Frame: Day 56 ]
   The anti-Sm14 IgG isotypes (Total IgG; IgG1; IgG3; IgG4; IgE) antibody response using an indirect ELISA
3. assessment of Immunogenicity 3 [ Time Frame: Day 84 ]
   The anti-Sm14 IgG isotypes (Total IgG; IgG1; IgG3; IgG4; IgE) antibody response using an indirect ELISA
4. assessment of Immunogenicity 4 [ Time Frame: Day 140 ]
   The anti-Sm14 IgG isotypes (Total IgG; IgG1; IgG3; IgG4; IgE) antibody response using an indirect ELISA
5. assessment of Immunogenicity 5 [ Time Frame: Day 168 ]
   The anti-Sm14 IgG isotypes (Total IgG; IgG1; IgG3; IgG4; IgE) antibody response using an indirect ELISA
6. assessment of Immunogenicity 6 [ Time Frame: Day 224 ]
   The anti-Sm14 IgG isotypes (Total IgG; IgG1; IgG3; IgG4; IgE) antibody response using an indirect ELISA
7. assessment of Immunogenicity 7 [ Time Frame: Day 308 ]
   The anti-Sm14 IgG isotypes (Total IgG; IgG1; IgG3; IgG4; IgE) antibody response using an indirect ELISA
8. assessment of Immunogenicity 8 [ Time Frame: Day 392 ]
   The anti-Sm14 IgG isotypes (Total IgG; IgG1; IgG3; IgG4; IgE) antibody response using an indirect ELISA
9. assessment of immunogenicity 9 [ Time Frame: Day 1 ]
   Measure expression change in membrane markers expression of PBMC under in vitro Sm14 antigen activation
10. assessment of immunogenicity 10 [ Time Frame: Day 84 ]
    Measure expression change in membrane markers expression of PBMC under in vitro Sm14 antigen activation (for Group Vacc3)
11. assessment of immunogenicity 11 [ Time Frame: Day 168 ]
    Measure expression change in membrane markers expression of PBMC under in vitro Sm14 antigen activation (for Group Vacc2+1)
12. assessment of immunogenicity 12 [ Time Frame: Day 1 ]
    12. Measure cytokine production (ELISA) by PBMC under in vitro Sm14 antigen activation
13. assessment of immunogenicity 13 [ Time Frame: Day 84 ]
    12. Measure cytokine production (ELISA) by PBMC under in vitro Sm14 antigen activation (for Group Vacc3)
14. assessment of immunogenicity 14 [ Time Frame: Day 168 ]
    12. Measure cytokine production (ELISA) by PBMC under in vitro Sm14 antigen activation (for Group Vacc2+1)

Secondary Outcome Measures :

1. Safety of the vaccine candidate Sm14 -1 [ Time Frame: from Day 1 to Day 442 ]
   The occurrence of study vaccine-related SAEs
2. Safety of the vaccine candidate Sm14 - 2 [ Time Frame: from Day 1 to Day 3 ]
   2. The occurrence of solicited injection site reactogenicity
3. Safety of the vaccine candidate Sm14 -3 [ Time Frame: from Day 28 to Day 30 ]
   The occurrence of solicited injection site reactogenicity
4. Safety of the vaccine candidate Sm14 -4 [ Time Frame: from Day 56 to Day 58 ]
   The occurrence of solicited injection site reactogenicity for Group Vacc3
5. Safety of the vaccine candidate Sm14 -5 [ Time Frame: from Day 140 to Day 142 ]
   The occurrence of solicited injection site reactogenicity for Group Vacc2+1
6. Safety of the vaccine candidate Sm14 _6 [ Time Frame: from Day 1 to Day 3 ]
   The occurrence of solicited injection site reactogenicity
7. Safety of the vaccine candidate Sm14 -7 [ Time Frame: from Day 28 to Day 30 ]
   The occurrence of solicited injection site reactogenicity
8. Safety of the vaccine candidate Sm14 -8 [ Time Frame: from Day 56 to Day 58 ]
   The occurrence of solicited injection site reactogenicity for Group Vacc3
9. Safety of the vaccine candidate Sm14 -9 [ Time Frame: from Day 140 to Day 142 ]
   The occurrence of solicited injection site reactogenicity for Group Vacc2+1

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 49 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Man living in villages in the Saint Louis region where schistosomiasis is endemic.
• Having an infectious history of schistosomiasis.
• Adult between 18 and 49 years old at the time of the first injection.
• Have received pre-treatment with PZQ four to eight weeks before inclusion.
• Consent signed by the volunteer after information.
• Satisfactory state of health, confirmed on clinical examination and following biological assessment (Vpi / W-1).
• Available for the duration of the trial.
• To be negative to the Covid-19 antigenic test

Exclusion Criteria (Non inclusion criteria) :

• Subject not meeting one of the inclusion criteria.
• Participation to a previous anti-schistosomiasis vaccine clinical trial.
• Participation in another ongoing clinical research
• Current or previous chronic administration (defined as more than 14 days) of immunosuppressive drugs or other immune modulating drugs.
• Known hypersensitivity to any component present in the Sm14 vaccine, or to any given vaccine, and / or history of allergic disease.
• Acute illness at the time of inclusion.
• Other conditions which, according to the PI, can potentially represent a danger to the subject to be included.

Contacts and Locations

Contacts

Contact: Miriam TENDLER; +55 21 994 417 749; mtendler@ioc.fiocruz.br

Contact: Marilia SIRIANNI; +55 21 2562 1273; sirianni@ioc.fiocruz.br

Locations

Senegal

Biomedical Research Center EPLS; Recruiting

Saint Louis, Senegal

Contact: Gilles RIVEAU, PharmD PhD +221 774228826 gilles.riveau@gmail.com

Contact: Anne-Marie SCHACHT, MS +221 339610377 am.schacht@gmail.com

Principal Investigator: Abdoulaye MBENGUE, MD

Sub-Investigator: Amadou Tidjani LY, MD

Sponsors and Collaborators

Oswaldo Cruz Foundation

Investigators

• Study Director: Gilles RIVEAU, PharmD PhD; Biomedical Research Center EPLS

More Information

• Responsible Party: MIRIAM TENDLER, MD, PhD, Oswaldo Cruz Foundation
• ClinicalTrials.gov Identifier: NCT05658614
• Other Study ID Numbers: Sm14-2c-Sn
• First Posted: December 21, 2022
• Last Update Posted: December 21, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Infections; Schistosomiasis; Schistosomiasis mansoni; Schistosomiasis haematobia; Trematode Infections; Helminthiasis; Parasitic Diseases; Vector Borne Diseases; Urinary Tract Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases