Auranofin for Giardia Protozoa

NCT02736968 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 15-0015
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 2

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.

Conditions

Amoebic Dysentery; Giardiasis

Keywords

Amebiasis; Auranofin; GI Protozoa; Giardiasis; Placebo-Controlled; Reprofiled Drug; Single-Blind

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Positive Rapid Enzyme Immunoassay (EIA) and Positive Antigen Detection EIA for Giardia and Resolution of Diarrhea (Less Than 3 Loose Stools/24 Hours)

  Diarrhea was assessed by self-report at each study visit. Resolution of diarrhea occurred when participants reported less than 3 loose stools in 24 hours.

  Day 5

• Number of Participants With Positive Rapid Enzyme Immunoassay (EIA) and Positive Antigen Detection EIA for Giardia at Enrollment With Parasitological Response (no Detection of Cysts or Trophozoites on Microscopic Exam or Negative Antigen Test)

  Participants provided stool samples on Day 5. Stool samples were assessed for parasitological response by detection of cysts or trophozoites via microscopic exam or a negative antigen test.

  Day 5

Secondary Outcomes (10)

• Proportion of Participants With Negative Giardia Stool Antigens

  Day 3 through Day 5

• Proportion of Symptomatic Participants With Positive Rapid EIA and Positive Antigen Detection EIA for Giardia and Trophozoites on Smear at Enrollment With Parasitological Response

  Day 3 through Day 5

• Proportion of Symptomatic Participants With Sustained Giardia Cure (no Detection of Trophozoites by Microscopic Exam)

  Day 14 through Day 28

• Giardia Trophozoite/Cyst Load by Quantitative Polymerase Chain Reaction (qPCR) in Stools of Symptomatic Participants

  Day 3 through Day 5

• Time to Resolution of Diarrhea (Less Than 3 Loose Stools/24 Hours)

  Day 1 through Day 28

Study Arms (4)

E. histolytica- Active

EXPERIMENTAL

N=34, 6mg auranofin daily x 7 days

Drug: Auranofin

E. histolytica- Placebo

PLACEBO COMPARATOR

N=34, 6mg placebo daily x 7 days

Other: Placebo

Giardia- Active

EXPERIMENTAL

N=34, 6mg auranofin daily x 5 days

Drug: Auranofin

Giardia- Placebo

PLACEBO COMPARATOR

N=34, 6mg placebo daily x 5 days

Other: Placebo

Interventions

Auranofin DRUG

Auranofin is a gold-containing chemical salt available as 3mg capsules

E. histolytica- Active; Giardia- Active

Placebo OTHER

Placebo

E. histolytica- Placebo; Giardia- Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written informed consent prior to initiation of any study procedures.
• Able to understand and comply with planned study procedures and be available for all study visits.
• Male or non-pregnant non-lactating females 18-65 years of age, inclusive. Females of reproductive potential currently using effective contraceptive methods are eligible.
• 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.
• 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

You may not qualify if:

• Vital signs (oral temperature, pulse, and blood pressure) are all within normal protocol-defined ranges.
• 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.
• Urinalysis with no greater than trace protein. If a high protein is confirmed to be due to menstruation, it should be repeated.
• 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.
• 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.
• Known intolerance of auranofin or gold compounds.
• 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.
• Use of metronidazole within the past 7 days.
• 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.
• Concurrent participation in other investigational protocols or receipt of an investigational product within the previous 30 days.
• History of alcohol or drug abuse within the last five years.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

International Center for Diarrheal Disease Research Bangladesh - Parasitology

Dhaka, 1212, Bangladesh

Location

Rajshahi Medical College Hospital

Rajshahi, Bangladesh

Location

MeSH Terms

Conditions

Dysentery, Amebic; Giardiasis; Amebiasis

Interventions

Auranofin

Condition Hierarchy (Ancestors)

Intestinal Diseases, Parasitic; Parasitic Diseases; Infections; Protozoan Infections; Dysentery; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Aurothioglucose; Organogold Compounds; Organometallic Compounds; Organic Chemicals

Results Point of Contact

• Title: Sharon Reed, MD
• Organization: University of California, San Diego

slreed@ucsd.edu

858-822-2808

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2016
• First Posted: April 13, 2016
• Study Start: November 6, 2016
• Primary Completion: March 10, 2021
• Study Completion: March 10, 2021
• Last Updated: January 26, 2023
• Results First Posted: January 26, 2023

Record last verified: 2020-04-21

Locations

BA (2)