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Sm-TSP-2 Schistosomiasis Vaccine in Healthy Ugandan Adults

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ClinicalTrials.gov Identifier: NCT03910972
Recruitment Status : Not yet recruiting
First Posted : April 10, 2019
Last Update Posted : April 11, 2019
Sponsor:
Collaborators:
George Washington University
Makerere University Walter Reed Project
Information provided by (Responsible Party):
Maria Elena Bottazzi PhD, Baylor College of Medicine

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.


Condition or disease Intervention/treatment Phase
Schistosomiasis Schistosoma Mansoni Biological: Sm-TSP-2/Alhydrogel® vaccine Biological: Sm-TSP-2/Alhydrogel® vaccine plus AP 10-701 Biological: ENGERIX-B Hepatitis B Vaccine Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 290 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase I/II Trial of the Safety, Immunogenicity, and Efficacy of the Sm-TSP-2/Alhydrogel® Schistosomiasis Vaccine in Healthy Exposed Ugandan Adults
Estimated Study Start Date : June 2019
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Algeldrate

Arm Intervention/treatment
Experimental: Part A, Group A (Sm-TSP-2/Alhydrogel 10 mcg)
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
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.

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

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

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

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

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

Active Comparator: Part A, Group G (HBV)
Hepatitis B Vaccine
Biological: ENGERIX-B Hepatitis B Vaccine
Recombinant hepatitis B vaccine containing 10 mcg recombinant hepatitis B surface antigen per dose

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

Active Comparator: Part B, Group I (HBV)
Hepatitis B Vaccine
Biological: ENGERIX-B Hepatitis B Vaccine
Recombinant hepatitis B vaccine containing 10 mcg recombinant hepatitis B surface antigen per dose




Primary Outcome Measures :
  1. Safety and Tolerability: frequency of local and systemic reactogenicity events [ Time Frame: 7 days post-vaccination ]
    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.

  2. Safety and Tolerability: frequency of unsolicited adverse events [ Time Frame: 28 days post-vaccination ]
    Frequency of unsolicited adverse events, graded by severity, from the time of each study vaccination through approximately 1 month after each study vaccination.

  3. Safety and Tolerability: frequency of vaccine-related Serious Adverse Events [ Time Frame: 23 months ]
    Frequency of study vaccine-related Serious Adverse Events from the time of the first study vaccination through the final study visit.

  4. Safety and Tolerability: frequency of clinical safety laboratory adverse events [ Time Frame: 7 days post-vaccination ]
    Frequency of clinical safety laboratory adverse events measured 7 days after each vaccination

  5. Safety and Tolerability: frequency of new-onset chronic medical conditions [ Time Frame: 23 months ]
    Frequency of new-onset chronic medical conditions, including Adverse Events of Special Interest, through the final study visit

  6. Efficacy: proportion of subjects with detectable S. mansoni eggs [ Time Frame: 12 and 23 months ]
    Proportion of subjects with detectable S. mansoni eggs at 12 and 23 months in fecal samples, as determined by Kato Katz fecal thick smear.

  7. Efficacy: mean S. mansoni eggs per gram of feces [ Time Frame: 12 and 23 months ]
    Mean S. mansoni eggs per gram as determined by fecal microscopy (Kato Katz fecal thick smear) at 12 and 23 months.

  8. Efficacy: Proportion of subjects with a positive CAA test [ Time Frame: 12 and 23 months ]
    Proportion of subjects with a positive CAA test at 12 and 23 months.


Secondary Outcome Measures :
  1. Immunogenicity: peak anti-Sm-TSP-2 IgG level [ Time Frame: Day 126 ]
    IgG level by qualified indirect ELISA on approximately Day 126

  2. Immunogenicity: anti-Sm-TSP-2 IgG levels over time [ Time Frame: 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. ]
    IgG antibody response measured by qualified indirect ELISA


Other Outcome Measures:
  1. Efficacy: CAA (Part B only) [ Time Frame: 12 and 23 months following final vaccination ]
    Proportion of subjects with a positive CAA test

  2. Efficacy: fecal Schistosomal DNA [ Time Frame: 12 and 23 months following final vaccination ]
    Levels of Schistosoma DNA in fecal samples, as measured by real-time PCR.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Provide written informed consent prior to any study procedures.
  2. Able to understand and comply with planned study procedures and be available for all study visits.
  3. Male or non-pregnant female aged 18 to 45, inclusive at the time of enrollment.
  4. Are in good health, as determined by vital signs (oral temperature, pulse, and blood pressure), medical history, and brief physical examination at screening.
  5. Vital signs (oral temperature, pulse, and blood pressure) are all within normal protocol-defined ranges.
  6. Laboratory tests (alanine aminotransferase [ALT], creatinine, white blood cell count (WBC), hemoglobin, and platelets) are all within protocol-defined reference ranges.
  7. Urinalysis with no greater than trace protein and negative for glucose.
  8. 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.
  9. Female subjects of childbearing potential must have a negative urine pregnancy test within 24 hours prior to study vaccination.
  10. Able to correctly answer all questions on the informed consent comprehension questionnaire.

Exclusion Criteria:

  1. Has the intention to become pregnant within 5 months after enrollment in this study.
  2. 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.
  3. Has an acute illness, including a documented oral temperature of 38.0°C or greater, within 72 hours prior to vaccination.
  4. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, diabetes, or renal disease by history, physical examination, and/or laboratory studies.
  5. Is immunosuppressed as a result of an underlying illness or treatment.
  6. 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.
  7. Positive test for HIV infection.
  8. Volunteer has had a history of alcohol or illicit drug abuse during the past 23 months.
  9. Received immunoglobulin or other blood products (with exception of Rho D immunoglobulin) within 90 days prior to study vaccination.
  10. History of a severe allergic reaction or anaphylaxis to known components of the study vaccines.
  11. 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.
  12. History of splenectomy.
  13. Is participating or plans to participate in another clinical trial with an interventional agent during the duration of the study.
  14. Received any licensed live vaccine within 30 days or any licensed inactivated vaccine within 14 days prior to the first study vaccination.
  15. Planned receipt of any vaccine from the first study vaccination through 28 days after the last study vaccination.
  16. Has any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations.
  17. Has any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
  18. Anti-Sm-TSP-2 IgE antibody level above ELISA reactivity threshold.

    Part A Only:

  19. Positive hepatitis B surface antigen (HBsAg).
  20. Positive confirmatory test for hepatitis C virus (HCV) infection.

    Part B Only:

  21. Negative for Schistosoma mansoni eggs, as assessed by the Kato Katz fecal thick smear during screening.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03910972


Contacts
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Contact: David J Diemert, MD 2022702393 ddiemert@gwu.edu
Contact: Samantha Daaka, MPH 2029947164 samdaaka@gwu.edu

Locations
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Uganda
Makerere University Walter Reed Project Not yet recruiting
Kampala, Uganda
Contact: Hannah Kibuuka, MD    +256-312-330-400    hkibuuka@muwrp.org   
Contact: Allan Tindikahwa, MD    +256-312-330-400    Atindikahwa@muwrp.org   
Sponsors and Collaborators
Baylor College of Medicine
George Washington University
Makerere University Walter Reed Project
Investigators
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Principal Investigator: Hannah Kibuuka, MD Makerere University Walter Reed Project

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Responsible Party: Maria Elena Bottazzi PhD, Co-Director, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT03910972     History of Changes
Other Study ID Numbers: TSP-18-03
First Posted: April 10, 2019    Key Record Dates
Last Update Posted: April 11, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data related to primary and secondary objectives will be made available within 12 months of finalization of the Clinical Study Report.
Time Frame: Within 12 months of finalization of the Clinical Study Report.

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

Additional relevant MeSH terms:
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Schistosomiasis
Trematode Infections
Helminthiasis
Parasitic Diseases
Vaccines
Aluminum Hydroxide
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic
Antacids
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Agents