A Phase I Study of the Safety, Reactogenicity, and Immunogenicity of Sm-TSP-2/Alhydrogel® With or Without GLA-AF for Intestinal Schistosomiasis in Healthy Adults

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Brief Title

A Phase I Study of the Safety, Reactogenicity, and Immunogenicity of Sm-TSP-2/Alhydrogel® With or Without GLA-AF for Intestinal Schistosomiasis in Healthy Adults

Official Title

A Phase I Study of the Safety, Reactogenicity, and Immunogenicity of Sm-TSP-2/Alhydrogel® With or Without GLA-AF for Intestinal Schistosomiasis in Healthy Adults

Brief Summary

      This is a Phase I, first-in-human study of a vaccine against S. mansoni infection.The study
      will recruit 72 healthy adult males and non-pregnant females from a single clinical center to
      test two formulations of Sm-TSP-2 vaccine (using the Alhydrogel® only, and using Alhydrogel®
      plus GLA-AF), each at 3 different doses: 10ug, 30ug, and 100ug. The primary objective is to
      assess the safety and reactogenicity of ascending doses of Sm-TSP-2/Alhydrogel® (10ug, 30ug,
      or 100ug) with or without GLA-AF vaccine given as three doses administered on Days 1, 57, and
      113.
    

Detailed Description

      This is a Phase I, first-in-human study of a vaccine against S. mansoni infection.The study
      will recruit 72 healthy adult males and non-pregnant females from a single clinical center to
      test two formulations of Sm-TSP-2 vaccine (using the Alhydrogel® only, and using Alhydrogel®
      plus GLA-AF), each at 3 different doses: 10ug, 30ug, and 100ug. The study will use a
      dose-escalation cohort design, in which escalation to the next dose cohort will be determined
      based on evaluation of pre-defined escalation criteria requiring 7 day safety data to be
      examined after all subjects in the current cohort have received their first dose of vaccine.
      For each Cohort (1-3), an initial 5 subjects (2 Sm-TSP-2/Alhydrogel®, 2
      Sm-TSP-2/Alhydrogel®/GLA-AF, and 1 placebo) will be enrolled, randomized, vaccinated, and
      have completed Visit 2 (Day 3), before enrolling the rest of the cohort. As with
      dose-escalation decisions, evidence of significant reactogenicity will require further review
      prior to proceeding.Recruitment and enrollment into the study will occur on an ongoing basis,
      with each cohort being recruited and vaccinated in sequence. All subjects will be assigned
      investigational vaccine or placebo by randomization, and a double-blind design will be used
      (i.e., neither the subject nor the investigator will be aware of the study product assigned:
      Sm-TSP-2/Alhydrogel®, Sm-TSP-2/Alhydrogel®/GLA-AF, or placebo). Each subject will receive 3
      vaccinations at Days 1, 57, and 113, and will be followed for a total of 12 months after the
      third dose. The study duration will be approximately 24 months, and subject participation
      duration will be approximately 16 months. The primary objective is to assess the safety and
      reactogenicity of ascending doses of Sm-TSP-2/Alhydrogel® (10ug, 30ug, or 100ug) with or
      without GLA-AF vaccine given as three doses administered on Days 1, 57, and 113. The
      secondary objectives include: (1) to assess the IgG antibody response using an indirect
      enzyme-linked immunosorbent assay (ELISA) at Day 127; (2) to assess the IgG antibody response
      using an indirect enzyme-linked immunosorbent assay (ELISA) at 14 days after dose one and two
      and Day 203 and 293 (3 and 6 months after the third dose) of Sm-TSP-2/Alhydrogel® (10ug,
      30ug, or 100ug) with or without GLA-AF; (3) To assess the duration of the IgG antibody
      response using an indirect enzyme-linked immunosorbent assay (ELISA) following receipt of
      three doses of Sm-TSP-2/Alhydrogel® (10ug, 30ug, or 100ug) with or without GLA-AF.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

The occurrence of new-onset chronic medical conditions (including AESI) through 12 months after the third study vaccination.

Secondary Outcome

 The IgG antibody response using an indirect enzyme-linked immunosorbent assay (ELISA) on the day of each dose, 14 days after each dose, and 3 and 6 months after the third dose of Sm-TSP-2/Alhydrogel (10ug, 30ug, or 100ug) with or without GLA-AF

Condition

Schistosomiasis

Intervention

Placebo

Study Arms / Comparison Groups

 Group A
Description:  N=10 subjects will receive single dose intramuscular (IM) 10mcg Sm-TSP-2/Alhydrogel® on Day1, 57 and 113

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

Other

Estimated Enrollment

72

Start Date

February 4, 2015

Completion Date

January 27, 2017

Primary Completion Date

January 27, 2017

Eligibility Criteria

        Inclusion Criteria:

        Subjects must meet all of the following inclusion criteria in order to be eligible for
        participation in this study. 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 50, inclusive. 4. Are in
        good health, as determined by vital signs (oral temperature, pulse, and blood pressure),
        medical history, and targeted physical examination based on medical history.1 Existing
        medical diagnoses or conditions (except those in the Subject Exclusion Criteria) must be
        deemed as stable chronic medical conditions. A stable chronic medical condition is defined
        as no change in prescription medication, dose, or frequency of medication in the last 3
        months (90 days) and health outcomes of the specific disease are considered to be within
        acceptable limits in the last 6 months (180 days). Any change due to change of health care
        provider, insurance company, or that is done for financial reasons, as long as in the same
        class of medication, will not be considered a violation of this inclusion criterion. Any
        change in prescription medication due to improvement of a disease outcome, as determined by
        the site principal investigator or appropriate sub-investigator, will not be considered a
        violation of this inclusion criterion. Subjects may be on chronic or as needed (prn)
        medications if, in the opinion of the site principal investigator or appropriate
        sub-investigator, they pose no additional risk to subject safety or assessment of
        reactogenicity and immunogenicity. Topical, nasal, and inhaled medications (with the
        exception of steroids as outlined in the Subjects Exclusion Criteria), vitamins, and
        contraceptives are permitted. 5. Vital signs (oral temperature, pulse, and blood pressure)
        are all within normal protocol-defined ranges. Note: The normal protocol-defined ranges for
        vital signs include (a) oral temperature less than 100.0°F, (b) pulse 50 to 100 bpm,
        inclusive, (c) systolic blood pressure 85 to 150 mmHg, inclusive, and (d) diastolic blood
        pressure 55 to 90 mmHg, inclusive. 6. Laboratory tests (alanine aminotransferase,
        creatinine, white blood cells, hemoglobin, and platelets) are all within normal
        protocol-defined reference ranges.33 The normal protocol-defined ranges for laboratory
        tests include (a) alanine aminotransferase (ALT) of 32 IU/L or less for females or 44 IU/L
        or less for males, (b) creatinine 1.0 mg/dL or less for females or 1.27 mg/dL or less for
        males, (c) white blood cells (WBC) between 3.4 x10^3/uL and 10.8 x10^3/uL, inclusive, (d)
        hemoglobin 11.1 g/dL or greater for females or 12.6 g/dL or greater for males, (e)
        platelets between 150 x10^3/uL and 379 x10^3/uL, inclusive. Laboratory test results for 2nd
        and 3rd vaccinations may be at Grade 1 if considered unrelated to study product. 7.
        Urinalysis with no greater than trace protein and negative for glucose. 8. Female subjects
        of childbearing potential4 must agree to practice highly effective contraception5 for a
        minimum of 30 days prior to study product exposure and through 30 days after last
        vaccination.4 Female subjects who are surgically sterile via tubal sterilization, bilateral
        oophorectomy or hysterectomy or who have been postmenopausal for greater than 1 year are
        not considered to be of childbearing potential.5 Note: Highly effective methods of
        contraception are defined as having low failure rates (i.e. less than 1% per year) when
        used consistently and correctly and may include, but are not limited to, abstinence from
        intercourse with a male partner, monogamous relationship with a vasectomized partner, mal e
        condoms or diaphragm with spermicide, intrauterine devices, and licensed hormonal methods.
        9. Female subjects of childbearing potential must have a negative urine pregnancy test
        within 24 hours prior to study vaccination.

        Exclusion Criteria:

        All subjects who meet any of the following exclusion criteria at baseline will be excluded
        from participation in the study. 1. Has had known infection due to S. mansoni or has
        traveled to an endemic area for S. mansoni infection and, during that travel, was
        potentially exposed to S. mansoni. 2. Has a positive urine pregnancy test prior to
        vaccination (if female of childbearing potential), or has the intention to become pregnant
        within 5 months after enrollment in this study. 3. 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. 4. Has an acute illness, including an oral temperature of
        100.0 degree F or greater, within 72 hours prior to vaccination. 5. Evidence of clinically
        significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, diabetes,
        or renal disease by history, physical examination, and/or laboratory studies. 6.6 Includes
        the conditions and diagnoses defined as AESI in Section 9.3.3. 6. Is immunosuppressed as a
        result of an underlying illness or treatment.7.7 Causes for immunosuppression may include,
        but are not limited to, poorly-controlled diabetes mellitus, cirrhosis, renal
        insufficiency, active neoplastic disease or a history of any hematologic malignancy,
        connective tissue disease, organ transplant. 7. Using or intends to continue using oral or
        parenteral steroids, high-dose inhaled steroids(> 800 microg/day of beclomethasone
        dipropionate or equivalent) or other immunosuppressive or cytotoxic drugs. 8. Positive
        hepatitis B surface antigen (HBsAg) 9. Positive confirmatory test for HIV infection 10.
        Positive confirmatory test for hepatitis C virus (HCV) infection 11. Volunteer has had a
        history of alcohol or illicit drug abuse during the past 24 months. 12. Received
        immunoglobulin or other blood products (with exception of Rho D immunoglobulin) within 90
        days prior to study vaccination. 13. History of a severe allergic reaction or anaphylaxis
        to known components of the vaccine 14. 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. Note: This includes, but is not limited to:
        known liver disease, renal disease, neurological disorders, visual field defects, cardiac
        disorders, pulmonary disorders, diabetes mellitus, and transplant recipients. 15. History
        of splenectomy 16. Plans to undergo surgery (elective or otherwise) from the time of
        enrollment through 1 month post dose 3 vaccination. 17. Is participating or plans to
        participate in another clinical trial with an interventional agent9 during the duration of
        the study. Note: This may include other licensed or unlicensed vaccines, drugs, biologics,
        devices, blood products, or medications. 18.Received any licensed live vaccine within 30
        days or any licensed inactivated vaccine within 14 days prior to the first study
        vaccination. Note: During influenza season, subjects will be offered seasonal influenza
        vaccine prior to enrollment into the study. 19. Planned receipt of any vaccine from the
        first study vaccination through 1 month after the last study vaccination. 20. Have any
        diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric
        diagnosis that may interfere with subject compliance or safety evaluations. 21. 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.
      

Gender

All

Ages

18 Years - 50 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02337855

Organization ID

13-0009

Secondary IDs

HHSN272200800002C

Responsible Party

Sponsor

Study Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)


Study Sponsor

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Verification Date

December 7, 2016