Sm-TSP-2 Schistosomiasis Vaccine in Healthy Ugandan Adults

NCT03910972 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: H-45791TSP-18-03
• Study Type: interventional
• Target: 290
• Locations: 1 country
• Sites: 1

Brief Summary

The study will recruit up to 290 healthy adult males and non-pregnant females into a two-part clinical trial of a vaccine to protect against schistosomiasis caused by infection with S. mansoni. Two formulations of the Sm-TSP-2 vaccine will be tested: one using Alhydrogel® only, and one using Alhydrogel® plus AP 10-701, each at 3 different doses of antigen: 10mcg, 30mcg, and 100mcg. The first part of the study will be a Phase I dose-escalation safety and immunogenicity study followed by a Phase IIb trial in which a larger number of adults will be enrolled to assess the impact of the vaccine on infection with S. mansoni. The impact of the vaccine on infection with S. haematobium will also be assessed although this will be exploratory given that potential cross-protection against this species is only hypothetical at this point.

Conditions

Schistosomiasis; Schistosoma Mansoni

Outcome Measures

Primary Outcomes (8)

• Safety and Tolerability: frequency of local and systemic reactogenicity events

  Frequency of solicited injection site and systemic reactogenicity, graded by severity, on the day of each study vaccination through 7 days after each study vaccination.

  7 days post-vaccination

• Safety and Tolerability: frequency of unsolicited adverse events

  Frequency of unsolicited adverse events, graded by severity, from the time of each study vaccination through approximately 1 month after each study vaccination.

  28 days post-vaccination

• Safety and Tolerability: frequency of vaccine-related Serious Adverse Events

  Frequency of study vaccine-related Serious Adverse Events from the time of the first study vaccination through the final study visit.

  23 months

• Safety and Tolerability: frequency of clinical safety laboratory adverse events

  Frequency of clinical safety laboratory adverse events measured 7 days after each vaccination

  7 days post-vaccination

• Safety and Tolerability: frequency of new-onset chronic medical conditions

  Frequency of new-onset chronic medical conditions, including Adverse Events of Special Interest, through the final study visit

  23 months

• Efficacy: proportion of subjects with detectable S. mansoni eggs

  Proportion of subjects with detectable S. mansoni eggs at 12 and 23 months in fecal samples, as determined by Kato Katz fecal thick smear.

  12 and 23 months

• Efficacy: mean S. mansoni eggs per gram of feces

  Mean S. mansoni eggs per gram as determined by fecal microscopy (Kato Katz fecal thick smear) at 12 and 23 months.

  12 and 23 months

• Efficacy: Proportion of subjects with a positive CAA test

  Proportion of subjects with a positive CAA test at 12 and 23 months.

  12 and 23 months

Secondary Outcomes (2)

• Immunogenicity: peak anti-Sm-TSP-2 IgG level

  Day 126

• Immunogenicity: anti-Sm-TSP-2 IgG levels over time

  Approximately 14 days after doses one and two and at Days 200, 290, 380 (Parts A and B) after final dose, and at Days 548, and 800 (Part B) after final dose.

Other Outcomes (2)

• Efficacy: CAA (Part B only)

  12 and 23 months following final vaccination

• Efficacy: fecal Schistosomal DNA

  12 and 23 months following final vaccination

Study Arms (9)

Part A, Group A (Sm-TSP-2/Alhydrogel 10 mcg)

EXPERIMENTAL

Sm-TSP-2/Alhydrogel Schistosomiasis Vaccine, delivered by IM injection on study days 0, 56, and 12; 10 mcg dose

Biological: Sm-TSP-2/Alhydrogel® vaccine

Part A, Group B (Sm-TSP-2/Alhydrogel 10 mcg + AP 10-701)

EXPERIMENTAL

Sm-TSP-2/Alhydrogel Schistosomiasis Vaccine plus AP 10-701, delivered by IM injection on study days 0, 56, and 12; 10 mcg dose

Biological: Sm-TSP-2/Alhydrogel® vaccine plus AP 10-701

Part A, Group C (Sm-TSP-2/Alhydrogel 30 mcg)

EXPERIMENTAL

Sm-TSP-2/Alhydrogel Schistosomiasis Vaccine, delivered by IM injection on study days 0, 56, and 12; 30 mcg dose

Biological: Sm-TSP-2/Alhydrogel® vaccine

Part A, Group D (Sm-TSP-2/Alhydrogel 30 mcg + AP 10-701)

EXPERIMENTAL

Sm-TSP-2/Alhydrogel Schistosomiasis Vaccine plus AP 10-701, delivered by IM injection on study days 0, 56, and 12; 30 mcg dose

Biological: Sm-TSP-2/Alhydrogel® vaccine plus AP 10-701

Part A, Group E (Sm-TSP-2/Alhydrogel 100 mcg)

EXPERIMENTAL

Sm-TSP-2/Alhydrogel Schistosomiasis Vaccine, delivered by IM injection on study days 0, 56, and 12; 100 mcg dose

Biological: Sm-TSP-2/Alhydrogel® vaccine

Part A, Group F (Sm-TSP-2/Alhydrogel 100 mcg + AP 10-701)

EXPERIMENTAL

Sm-TSP-2/Alhydrogel Schistosomiasis Vaccine plus AP 10-701, delivered by IM injection on study days 0, 56, and 12; 100 mcg dose

Biological: Sm-TSP-2/Alhydrogel® vaccine plus AP 10-701

Part A, Group G (HBV)

ACTIVE COMPARATOR

Hepatitis B Vaccine

Biological: ENGERIX-B Hepatitis B Vaccine

Part B, Group H (Sm-TSP-2/Alhydrogel +/- AP 10-701)

EXPERIMENTAL

Sm-TSP-2/Alhydrogel Schistosomiasis Vaccine, with or without AP 10-701, dose and formulation determined in Part A

Biological: Sm-TSP-2/Alhydrogel® vaccine

Part B, Group I (HBV)

ACTIVE COMPARATOR

Hepatitis B Vaccine

Biological: ENGERIX-B Hepatitis B Vaccine

Interventions

Sm-TSP-2/Alhydrogel® vaccine BIOLOGICAL

The Sm-TSP-2/Alhydrogel® candidate vaccine contains recombinant Sm-TSP-2 adsorbed onto aluminum hydroxide gel (Alhydrogel®) and suspended in a solution containing 10mM imidazole buffer containing 2mM phosphate and 15% sucrose, with pH 7.4 ± 0.1. The final concentrations of Sm-TSP-2 and Alhydrogel® in the drug product are 0.1mg/ml and 0.8mg/ml respectively.

Part A, Group A (Sm-TSP-2/Alhydrogel 10 mcg); Part A, Group C (Sm-TSP-2/Alhydrogel 30 mcg); Part A, Group E (Sm-TSP-2/Alhydrogel 100 mcg); Part B, Group H (Sm-TSP-2/Alhydrogel +/- AP 10-701)

Sm-TSP-2/Alhydrogel® vaccine plus AP 10-701 BIOLOGICAL

The Sm-TSP-2/Alhydrogel® candidate vaccine co-administered with the immunostimulant, AP 10-701. b) AP 10-701, also known as Gluco-Pyranosylphospho-Lipid A Aqueous Formulation (GLA-AF), is a Toll-like Receptor-4 agonist. Point-of-injection formulations with this immunostimulant will be prepared immediately prior to vaccination by adding an appropriate volume of AP 10-701 to Sm-TSP-2/Alhydrogel® and withdrawing an appropriate volume to administer the desired amount of Sm-TSP-2 plus 5µg GLA-AF.

Part A, Group B (Sm-TSP-2/Alhydrogel 10 mcg + AP 10-701); Part A, Group D (Sm-TSP-2/Alhydrogel 30 mcg + AP 10-701); Part A, Group F (Sm-TSP-2/Alhydrogel 100 mcg + AP 10-701)

ENGERIX-B Hepatitis B Vaccine BIOLOGICAL

Recombinant hepatitis B vaccine containing 10 mcg recombinant hepatitis B surface antigen per dose

Part A, Group G (HBV); Part B, Group I (HBV)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provide written informed consent prior to any study procedures.
• Able to understand and comply with planned study procedures and be available for all study visits.
• Male or non-pregnant female aged 18 to 45, inclusive at the time of enrollment.
• Are in good health, as determined by vital signs (oral temperature, pulse, and blood pressure), medical history, and brief physical examination at screening.
• Vital signs (oral temperature, pulse, and blood pressure) are all within normal protocol-defined ranges.
• Laboratory tests (alanine aminotransferase \[ALT\], creatinine, white blood cell count (WBC), hemoglobin, and platelets) are all within protocol-defined reference ranges.
• Urinalysis with no greater than trace protein and negative for glucose.
• Female subjects of childbearing potential must agree to practice highly effective contraception for a minimum of 30 days prior to first vaccination and for 30 days after last vaccination.
• Female subjects of childbearing potential must have a negative urine pregnancy test within 24 hours prior to study vaccination.
• Able to correctly answer all questions on the informed consent comprehension questionnaire.

You may not qualify if:

• Has the intention to become pregnant within 5 months after enrollment in this study.
• Female subjects who are breastfeeding or plan to breastfeed at any given time from the first study vaccination until 30 days after their last study vaccination.
• Has an acute illness, including a documented oral temperature of 38.0°C or greater, within 72 hours prior to vaccination.
• Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, diabetes, or renal disease by history, physical examination, and/or laboratory studies.
• Is immunosuppressed as a result of an underlying illness or treatment.
• Using or intends to continue using oral or parenteral steroids, high-dose inhaled steroids (\>800 μg/day of beclomethasone dipropionate or equivalent) or other immunosuppressive or cytotoxic drugs.
• Positive test for HIV infection.
• Volunteer has had a history of alcohol or illicit drug abuse during the past 23 months.
• Received immunoglobulin or other blood products (with exception of Rho D immunoglobulin) within 90 days prior to study vaccination.
• History of a severe allergic reaction or anaphylaxis to known components of the study vaccines.
• Has an acute or chronic medical condition that, in the opinion of the investigator, would render participation in this study unsafe or would interfere with the evaluation of responses.
• History of splenectomy.
• Is participating or plans to participate in another clinical trial with an interventional agent during the duration of the study.
• Received any licensed live vaccine within 30 days or any licensed inactivated vaccine within 14 days prior to the first study vaccination.
• Planned receipt of any vaccine from the first study vaccination through 28 days after the last study vaccination.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• George Washington University: collaborator
• Makerere University Walter Reed Project: collaborator

Study Sites (1)

Makerere University Walter Reed Project

Kampala, Uganda

Location

MeSH Terms

Conditions

Schistosomiasis

Condition Hierarchy (Ancestors)

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

Study Officials

• Hannah Kibuuka, MD

  Makerere University Walter Reed Project

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-Director

Study Record Dates

• First Submitted: April 9, 2019
• First Posted: April 10, 2019
• Study Start: October 7, 2019
• Primary Completion: November 13, 2024
• Study Completion: November 13, 2024
• Last Updated: November 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Time Frame: Within 12 months of finalization of the Clinical Study Report.

Locations

UG (1)