Sm-p80 Schistosomiasis Challenge Study

Schistosomiasis Clinical Trial

Official title:

Safety and Preliminary Efficacy of Sm-p80 + GLA-SE (SchistoShield®) Vaccine Against Controlled Human Schistosome Infection in Healthy, Schistosoma-naïve Adults

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05999825
• Other study ID #: Sm-p80
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: September 2024
• Est. completion date: September 2025

Study information

• Verified date: October 2023
• Source: Leiden University Medical Center
• Contact: Meta Roestenberg, Prof
• Phone: +31715269111
• Email: M.Roestenberg[@]lumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to learn about the Sm-p80 + GLA-SE (Schistoshield®) vaccine in healthy participants who have not had schistosomiasis before. The main questions it aims to answer are: - if the vaccine is safe - if after vaccinated people start producing antibodies - if the vaccine works against schistosomiasis. Participants will receive three vaccines (or placebo) and are then exposed to 20 male Schistosoma cercariae. Afterwards they are treated with praziquantel to cure the infection. Researchers will compare the group vaccinated with Schistoshield® and placebo (fake vaccination) to see if the vaccine has worked.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 48
• Est. completion date: September 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. Subject is aged = 18 and = 45 years and in good health.

2. Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby.

3. Subject is able to communicate well with the investigator, is available to attend all study visits.

4. Subject will not travel to Schistosoma-endemic countries up until treatment at week 24.

5. Subject agrees to refrain from blood and plasma donation to Sanquin or for other purposes throughout the study period.

6. For female subjects: subject agrees to use adequate contraception and not to breastfeed for the duration of study.

7. Subject has signed informed consent.

Exclusion Criteria:

1. Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine, malignant, haematological, infectious, immune-deficient, (severe) psychiatric and other disorders, which could compromise the health of the participant during the study or interfere with the interpretation of the study results. These include, but are not

limited to, any of the following:

• body weight <50 kg or Body Mass Index (BMI) <18.0 or >35.0 kg/m2 at screening;
• positive HIV, HBV or HCV screening tests;
• the use of immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted) or expected use of such during the study period;
• history of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years;
• any history of treatment for severe psychiatric disease by a psychiatrist in the past year;
• history of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset.

2. The chronic use of any drug known to interact with praziquantel, artesunate or lumefantrine metabolism (e.g. phenytoïn, carbamazepine, phenobarbital, primidon, dexamethason, rifampicine, cimetidine, flecaïnide, metoprolol, imipramine, amitriptyline, clomipramine, class IA and III anti-arrythmics, antipsychotics, antidepressants, macrolides, fluorchinolones, imidazole- and triazole antimycotics, antihistamines). Because lumefantrine may cause extension of QT-time, chronic use of drugs with effect on QT interval will result in exclusion from study participation.

3. Any planned vaccination within 28 days before the start of the trial until the end of the immunisation phase (week 12), with the exception of SARS-CoV-2 vaccines or influenza vaccines.

4. For female subjects: positive serum pregnancy test on the day before first immunisation.

5. Any history of schistosomiasis or treatment for schistosomiasis.

6. Positive serology for schistosomiasis or elevated serum CAA at screening.

7. Known hypersensitivity to or contra-indications (including co-medication) for use of praziquantel, artesunate or lumefantrine.

8. Being an employee or student of the department of Parasitology or Infectious diseases of the LUMC.

Related Conditions & MeSH terms

• Schistosoma Mansoni
• Schistosomiasis

Intervention

Biological:
• Sm-p80 + GLA-SE Vaccine
30 µg Sm-p80 + 5 µg GLA-SE

Other:
• Placebo
0.9% Sterile Normal Saline

Biological:
• Schistosoma mansoni infection
20 viable male Schistosoma mansoni cercariae of the Puerto Rican strain

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Leiden University Medical Center	MRC/UVRI and LSHTM Uganda Research Unit, Texas Tech University Health Sciences Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Time to CAA positivity	Comparison of time to positive serum CAA test between the vaccine and placebo groups after exposure to male Sm cercariae at week 12	week 12-24
Other	Peak CAA levels	Comparison of peak serum CAA concentrations between the vaccine and placebo groups after exposure to male Sm cercariae at week 12	week 12-24
Other	Eosinophils	Comparison of peak eosinophil counts between the vaccine and placebo groups after exposure to male Sm cercariae at week 12	week 12-24
Other	Antibody responses	Comparison of (glycan) antibody responses directed against Sm antigens between the vaccine and placebo participants as well as between protected and non-protected participants after exposure to male Sm cercariae at week 12 using protein and glycan arrays	week 0-24
Other	Cellular responses	Comparison of cellular responses directed against Sm antigens between the vaccine and placebo groups after immunisation and after controlled human infection with Sm cercariae, as well as between protected and non-protected participants	week 0-24
Other	In vitro killing	Enumeration of the ability of Sm-p80-specific antibodies from human subjects to kill schistosome larvae in vitro from sera collected prior to each vaccination	week 0-24
Other	Transcriptomic profile	Identification, characterization and comparison of gene expression changes as measured using RNA-seq analysis from PBMC between placebo and vaccine groups	week 0-24
Primary	Vaccine efficacy	The protective efficacy of Sm-p80 + GLA-SE to male Sm cercariae measured by the difference in frequency of serum CAA positivity (=1.0 pg/mL) between the vaccine group and placebo	week 12-24, i.e. after challenge
Secondary	Safety of (repeated) immunisation	Frequency and severity of adverse events after (repeated) immunisation with Sm-p80 + GLA-SE	week 0-12
Secondary	Immunogenicity	Anti-Sm-p80 IgG antibody titres after (repeated) immunisation with Sm-p80 + GLA-SE measured by ELISA	week 0-24