Sm-TSP-2 Schistosomiasis Vaccine in Healthy Ugandan Adults

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Brief Title

Sm-TSP-2 Schistosomiasis Vaccine in Healthy Ugandan Adults

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

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.
    

Detailed Description

      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.

      Part A: double blind (within cohort), randomized, controlled, dose-escalation Phase 1b
      clinical trial in S. mansoni exposed adults living in the area of Kampala, Uganda. In each of
      3 cohorts, subjects will be randomly assigned to 1 of 3 groups: Sm-TSP-2/Alhydrogel®,
      Sm-TSP-2/Alhydrogel®/AP 10-701, or the licensed Hepatitis B vaccine (up to 12 subjects per
      study vaccine group and 6 subjects in the Hepatitis B vaccine group). Subjects will receive
      three doses of the assigned vaccine delivered intramuscularly at approximately Days 0, 56,
      and 112.

      Safety will be measured from the time of each study vaccination (Days 0, 56, 112 [Visits 2,
      7, 12]) through 7 days after each study vaccination by the occurrence of solicited injection
      site and systemic reactogenicity events. Unsolicited non-serious adverse events (AEs) will be
      collected from the time of each study vaccination through approximately 28 days after each
      study vaccination. New-onset chronic medical conditions (including adverse events of special
      interest [AESI]) and serious adverse events (SAEs) will be collected from the time of the
      first study vaccination (Day 0 [Visit 2]) through approximately 9 months after the third
      study vaccination (Day 380 [Visit 19]). Clinical laboratory evaluations for safety will be
      performed on venous blood collected approximately 7 days after each study vaccination.

      Immunogenicity testing will include IgG antibody responses to Sm-TSP-2 by a qualified
      indirect ELISA on serum obtained prior to each study vaccination (Days 0, 56, 112) and at
      time points after each vaccination.

      Ninety subjects will be enrolled into 3 groups of 30. Recruitment and enrollment into the
      study will occur on an ongoing basis, with each group being recruited and vaccinated in
      sequence.

      Part A of the study is a dose escalation trial in which escalation to the next dose cohort
      will be determined based on evaluation of pre-defined escalation criteria, which will be
      evaluated 7 days after all subjects in the currently active cohort have received their first
      dose of vaccine. Within each cohort, the assignment to Alhydrogel®, Alhydrogel®/AP 10-701, or
      Hepatitis B vaccine will be randomized and double-blinded (i.e., neither the subject nor the
      investigator will be aware of the formulation assigned). The study will proceed as follows:

        1. Cohort 1, N=30 [10mcg Sm-TSP-2/Alhydrogel® (n=12) or 10mcg Sm-TSP-2/Alhydrogel®/ AP
           10-701 (n=12) or Hepatitis B vaccine (n=6)]

             1. Enroll, randomize, and administer first dose of study vaccine or Hepatitis B
                vaccine to initial 6 subjects

             2. After initial 6 subjects have completed Visit 3, administer the first dose of study
                vaccine or Hepatitis B vaccine to the remaining 24 subjects

             3. Assess 7 day post dose 1 safety data for all subjects

             4. Make escalation decision

        2. Cohort 2, N=30 [30mcg Sm-TSP-2/Alhydrogel® (n=12) or 10mcg Sm-TSP-2/Alhydrogel®/AP
           10-701 (n=12) or Hepatitis B vaccine (n=6)]

             1. Enroll, randomize, and administer first dose of study vaccine or Hepatitis B
                vaccine to initial 6 subjects

             2. After initial 6 subjects have completed Visit 3, administer the first dose of study
                vaccine or Hepatitis B vaccine to the remaining 24 subjects

             3. Assess 7 day post dose 1 safety data for all subjects

             4. Make escalation decision

        3. Cohort 3, N=30 [100mcg Sm-TSP-2/Alhydrogel® (n=12) or 10mcg Sm-TSP-2/Alhydrogel®/AP
           10-701 (n=12) or Hepatitis B vaccine (n=6)]

             1. Enroll, randomize, and administer first dose of study vaccine or Hepatitis B
                vaccine to initial 6 subjects

             2. After initial 6 subjects have completed Visit 3, administer the first dose of study
                vaccine or Hepatitis B vaccine to remaining 24 subjects

             3. Assess 7 day post dose 1 safety data for all subjects

             4. Complete follow-up for all subjects

             5. Close the study

      Part B: double blind, randomized, controlled, dose-escalation Phase IIb clinical trial in
      adults living in the area of Kampala, Uganda, who reside in S. mansoni endemic areas with
      greater than or equal to 25% prevalence in children aged 5-15 years of age. In this part of
      the study, up to 200 eligible Schistosoma-positive (by Kato Katz fecal thick smear or CAA)
      adult volunteers will be progressively enrolled and randomized to receive either
      Sm-TSP-2/Alhydrogel® (with or without AP 10-701) or the Hepatitis B comparator vaccine, in a
      1:1 fashion. The dose and formulation (i.e., with or without the point-of-injection addition
      of AP 10-701) of Sm-TSP-2/Alhydrogel® that will be tested in this part of the study will be
      chosen based on the interim results of Part A of the trial after all participants have
      received their third dose of vaccine. All participants in Part B will be treated with
      praziquantel prior to receipt of the first vaccination.

      Interim safety and anti-Sm-TSP-2 IgG antibody results up to and including Day 126 of Part A
      of the trial will be evaluated to determine the dose that will be tested in Part B.

      Two hundred subjects will be enrolled in Part B. The 12 subjects in Part A who received the
      same dose/formulation of Sm-TSP-2/Alhydrogel® that is chosen for Part B will be offered the
      opportunity to transition to Part B for the remainder of their participation in the study.

      Recruitment and enrollment into the study will occur on an ongoing basis, with participants
      being recruited, randomized and vaccinated in sequence. Within Part B, the assignment to
      Sm-TSP-2/Alhydrogel® or Hepatitis B vaccine will be randomized and double-blinded (i.e.,
      neither the subject nor the investigator will be aware of the formulation assigned). Part B
      of the study will proceed as follows:

      1. Cohort 4, N=200 [Sm-TSP-2/Alhydrogel® [dose and formulation TBD] (n=100) or Hepatitis B
      vaccine (n=100)]

      Subjects will receive three doses of the assigned vaccine delivered intramuscularly at
      approximately Days 0, 56, and 112.

      Safety will be measured from the time of each study vaccination (Days 0, 56, 112 [Visits 2,
      7, 12]) through 7 days after each study vaccination by the occurrence of solicited injection
      site and systemic reactogenicity events. Unsolicited non-serious adverse events (AEs) will be
      collected from the time of each study vaccination through approximately 28 days after each
      study vaccination. New-onset chronic medical conditions (including adverse events of special
      interest [AESI]) and serious adverse events (SAEs) will be collected from the time of the
      first study vaccination (Day 0 [Visit 2]) through approximately 23 months after the third
      study vaccination (Day 800 [Visit 21]). Clinical laboratory evaluations for safety will be
      performed on venous blood collected approximately 7 days after each study vaccination.

      Immunogenicity testing will include IgG antibody responses to Sm-TSP-2 by a qualified
      indirect ELISA on serum obtained prior to each study vaccination (Days 0, 56, 112) and at
      time points after each vaccination.

      Efficacy will be evaluated by measuring the impact of vaccination with Sm-TSP-2/Alhydrogel®
      on fecal and urine Schistosoma egg counts and CAA positivity. After final vaccination, fecal
      and urine samples will be collected at 12 and 23 months following the final vaccination to
      determine rates and intensities of re-infection. The primary endpoint to determine the impact
      of vaccination on infection with S. mansoni will be incidence of infection as determined by a
      positive CAA test or Kato-Katz fecal thick smear. The impact of vaccination on infection with
      S. haematobium will be assessed as an exploratory endpoint, by means of urine microscopy for
      schistosome eggs.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Safety and Tolerability: frequency of local and systemic reactogenicity events

Secondary Outcome

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

Condition

Schistosomiasis

Intervention

Sm-TSP-2/Alhydrogel® vaccine

Study Arms / Comparison Groups

 Part A, Group A (Sm-TSP-2/Alhydrogel 10 mcg)
Description:  Sm-TSP-2/Alhydrogel Schistosomiasis Vaccine, delivered by IM injection on study days 0, 56, and 12; 10 mcg dose

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

290

Start Date

October 7, 2019

Completion Date

October 2023

Primary Completion Date

October 2022

Eligibility 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.
      

Gender

All

Ages

18 Years - 45 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Hannah Kibuuka, MD, 2022702393, [email protected]

Location Countries

Uganda

Location Countries

Uganda

Administrative Informations


NCT ID

NCT03910972

Organization ID

TSP-18-03


Responsible Party

Principal Investigator

Study Sponsor

Baylor College of Medicine

Collaborators

 George Washington University

Study Sponsor

Hannah Kibuuka, MD, Principal Investigator, Makerere University Walter Reed Project


Verification Date

January 2020