Auranofin for Giardia Protozoa

Brief Title

Auranofin for Giardia Protozoa

Official Title

Phase IIa Randomized, Single-Blinded, Placebo-Controlled Clinical Trial of the Reprofiled Drug Auranofin for GI Protozoa

Brief Summary

      This is a phase IIa, randomized, placebo-controlled, single-blinded superiority treatment
      study in males and non-pregnant females, 18 to 65 years of age who are in good health. This
      study is designed to compare placebo to once daily doses of 6mg auranofin for adults with
      amebiasis or giardiasis. A sample size of 68 subjects enrolled with amebiasis (34 per arm)
      and 68 with giardiasis (34 per arm); Power based on 60 subjects with amebiasis and 60 with
      giardiasis completing the study.Eligible subjects will be randomly assigned to a treatment
      group with auranofin (6 mg orally once daily for 5 days for giardiasis or 7 days for
      amebiasis) compared to a placebo group receiving similar but not identical placebo capsules.
      Projected duration of subject participation will be approximately 30 days of face to face
      visits, including the pre-enrollment screening period of up to 4 days. It is anticipated that
      it will take approximately 3.5 years to finish the study. Primary objectives are: 1) to
      compare the proportion of subjects with stools positive by rapid Enzyme Immunoassay (EIA) and
      positive antigen detection EIA for E. histolytica at enrollment with resolution of diarrhea
      (less than 3 loose stools/24 hrs) by Day 7 for E. histolytica infections. 2) to compare the
      proportion of subjects with stools positive by rapid EIA and positive antigen detection EIA
      for Giardia at enrollment with resolution of diarrhea (less than 3 loose stools/24 hrs) by
      Day 5 for Giardia infections.
    

Detailed Description

      This is a phase IIa, randomized, placebo-controlled, single-blinded superiority treatment
      study in males and non-pregnant females, 18 to 65 years of age who are in good health. This
      study is designed to compare placebo to once daily doses of 6mg auranofin for adults with
      amebiasis or giardiasis. A sample size of 68 subjects enrolled with amebiasis (34 per arm)
      and 68 with giardiasis (34 per arm); Power based on 60 subjects with amebiasis and 60 with
      giardiasis completing the study. Eligible subjects will be randomly assigned to a treatment
      group with auranofin (6 mg orally once daily for 5 days for giardiasis or 7 days for
      amebiasis) compared to a placebo group receiving similar but not identical placebo capsules.
      Projected duration of subject participation will be approximately 30 days of face to face
      visits, including the pre-enrollment screening period of up to 4 days. It is anticipated that
      it will take approximately 3.5 years to finish the study. Primary objectives are: 1) to
      compare the proportion of subjects with stools positive by rapid Enzyme Immunoassay (EIA) and
      positive antigen detection EIA for E. histolytica at enrollment with resolution of diarrhea
      (less than 3 loose stools/24 hrs) by Day 7 for E. histolytica infections. 2) to compare the
      proportion of subjects with stools positive by rapid EIA and positive antigen detection EIA
      for Giardia at enrollment with resolution of diarrhea (less than 3 loose stools/24 hrs) by
      Day 5 for Giardia infections. Secondary objectives for E. histolytica infections are: 1) to
      compare the proportion of subjects with stools positive by rapid EIA and positive antigen
      detection EIA for E. histolytica and trophozoites on smear at enrollment with parasitological
      response (no detection of trophozoites of E. histolytica on microscopic exam) by Day 7; 2) to
      compare the proportion of subjects with stools positive rapid EIA and positive antigen
      detection EIA for E. histolytica and trophozoites on smear at enrollment with parasitological
      response (no detection of trophozoites on microscopic exam or negative antigen detection) by
      Days 3 and 5; 3) to compare the rate of decrease of trophozoites/cyst load by Quantitative
      Polymerase Chain Reaction (qPCR) in stools by Days 3, 5, and 7; 4) to compare the proportion
      of subjects with negative stool antigen tests by days 3, 5, 7, and 14; 5) to compare the
      proportion of subjects with sustained cure (no detection of trophozoites by microscopic exam)
      at 14 and 28 days; 6) to compare the proportion of subjects with relapse (same strain) or
      re-infection (new strain) with positive stools at 14 and 28 days by genotyping the initial
      vs. subsequent strain; 7) to compare the time to resolution of diarrhea (less than 3 loose
      stools/24 hours). Secondary objectives for Giardia infections are: 1) to compare the
      proportion of subjects with parasitological response (no detection of trophozoites on
      microscopic exam ) on Day 3, and 5; 2) to compare the rate of decrease of trophozoites/cyst
      load by qPCR in stools by Days 3 and 5; 3) to compare the proportion of subjects with
      negative stool antigens by days 3 and 5; 4) to compare the proportion of subjects with
      sustained cure (no detection of trophozoites by microscopic exam) at 14 and 28 days; 5) to
      compare the proportion of subjects with relapse (same strain) or re-infection (new strain)
      with positive stools at 14 and 28 days by genotyping the initial vs. subsequent strain; 6) to
      compare the time to resolution of diarrhea (less than 3 loose stools/24 hours).
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Proportion of subjects with positive rapid Enzyme Immunoassay (EIA) and positive antigen detection EIA for Giardia and resolution of diarrhea (less than 3 loose stools/24 hours)

Secondary Outcome

 Proportion of subjects with negative E. histolytica stool antigen test

Condition

Amoebic Dysentery

Intervention

Auranofin

Study Arms / Comparison Groups

 E. histolytica- Active
Description:  N=34, 6mg auranofin daily x 7 days

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

Drug

Estimated Enrollment

136

Start Date

August 19, 2016

Completion Date

November 30, 2020

Primary Completion Date

November 30, 2020

Eligibility Criteria

        Inclusion Criteria:

          1. Provide written informed consent prior to initiation of 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 non-lactating females 18-65 years of age, inclusive. Females of
             reproductive potential currently using effective contraceptive methods are eligible.

          4. Amebiasis or giardiasis identified by rapid Enzyme Immunoassay (EIA) and positive
             antigen detection EIA of stool

             - if a subject is infected with both E. histolytica and Giardia, they will be enrolled
             in the E. histolytica study arm. Once the Entamoeba study arm is fully enrolled, any
             subsequent dual infected subjects will be enrolled in the Giardia arm. If a subject is
             infected with both Giardia and Cryptosporidium, they will not be enrolled.

          5. Has diarrhea (defined as three or more loose stools) in the past 24 hrs, but is
             assessed to be clinically stable and in otherwise good health

             - as determined by medical history and targeted physical examination, if indicated
             based on medical history, to evaluate acute or currently ongoing chronic medical
             diagnoses or conditions that would affect the assessment of eligibility and safety of
             subjects. 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. Topical, nasal, and
             inhaled medications, vitamins, and contraceptives are permitted.

          6. Vital signs (oral temperature, pulse, and blood pressure) are all within normal
             protocol-defined ranges.

          7. Laboratory tests (blood urea nitrogen, creatinine, aspartate transaminase (AST),
             alanine transaminase (ALT), white blood cells, platelets, and hemoglobin) are all
             within protocol-defined ranges. Subjects will be eligible for enrollment with the
             following laboratory values: blood urea nitrogen less than or equal to 30 mg/dL,
             creatinine less than or equal to 133 umol/L, AST or ALT less than or equal to 70.0
             U/L, white cell count between 3.5 and 13.0 inclusive (10^9/L), platelets between 131
             and 550 (10^9/L), hemoglobin between 11.0 and 18.0 gm/dL inclusive.

          8. Urinalysis with no greater than trace protein. If a high protein is confirmed to be
             due to menstruation, it should be repeated.

          9. Women of reproductive potential must have a negative urine pregnancy test within 72
             hours of starting study medications.

             - Female subjects who are surgically sterile via tubal sterilization, bilateral
             oophorectomy or hysterectomy who have been postmenopausal for greater than 1 year are
             not considered to be of reproductive potential.

         10. Female subjects participating in sexual activity that could lead to pregnancy must be
             using and continue to use highly effective contraception for a total of 4 months after
             enrollment.

               -  Highly effective methods of contraception are defined as having low failure rates
                  (i.e. less than 1 percent per year) when used consistently and correctly and may
                  include, but are not limited to, abstinence from intercourse, monogamous
                  relationship with a vasectomized partner, male condoms with spermicide, diaphragm
                  with spermicide, intrauterine devices, and licensed hormonal methods. Females on
                  effective forms of birth control will continue while on the study and for the
                  follow-up period of 4 months total. The method and compliance of birth control
                  used will be confirmed and documented at all study visits.

        Exclusion Criteria:

          1. Known intolerance of auranofin or gold compounds.

          2. Pregnant or breastfeeding women or women of reproductive potential not using effective
             contraception or who plan to become pregnant or breastfeed at any given time during
             the study or within 3 months of study completion.

          3. Use of metronidazole within the past 7 days.

          4. 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.

          5. Concurrent participation in other investigational protocols or receipt of an
             investigational product within the previous 30 days.

          6. History of alcohol or drug abuse within the last five years.
      

Gender

All

Ages

18 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

, 18588222808, [email protected]

Location Countries

Bangladesh

Location Countries

Bangladesh

Administrative Informations


NCT ID

NCT02736968

Organization ID

15-0015


Responsible Party

Sponsor

Study Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)


Study Sponsor

, , 


Verification Date

April 21, 2020