Cholera Anti-Secretory Treatment Trial

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Brief Title

Cholera Anti-Secretory Treatment Trial

Official Title

A Phase 2a Randomized, Single-Center, Double-Blind, Placebo Controlled Study to Evaluate the Safety and Preliminary Efficacy of Oral iOWH032 Against Cholera Diarrhea in a Controlled Human Infection Model

Brief Summary

      This trial was designed to assess safety and preliminary efficacy of oral doses of iOWH032 on
      diarrhea output and clinical symptoms after a cholera challenge in healthy adult
      participants.
    

Detailed Description

      The study consists of a screening phase, an inpatient containment period with challenge with
      Vibrio cholerae on Day 1 followed by treatment with iOWH032 or placebo and a post-challenge
      observation period until discharge, an outpatient follow-up period of at least 28 days, and a
      final follow-up (by telephone) 6 months post-challenge (Day 180) for the collection of
      serious adverse events.

      Participants will be randomized 1:1 to receive either iOWH032 500 mg every 8 hours for three
      days or matching placebo. Blinded therapeutic dosing will start at the onset of diarrhea or
      by 48 hours after ingesting the challenge inoculum of V. cholerae. The observation and
      management of cholera diarrhea and symptomatology will occur on an inpatient isolation
      research ward over a duration of approximately 11 days, including a three-day course of
      antibiotics to treat all participants prior to discharge from the inpatient unit.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Diarrheal Stool Output Rate

Secondary Outcome

 Percentage of Participants With Moderate to Severe Diarrhea With Onset Within 48 Hours Following Cholera Challenge

Condition

Cholera

Intervention

iOWH032

Study Arms / Comparison Groups

 iOWH032
Description:  On Day 1, participants were challenged with 10^6 colony-forming units (CFU) of freshly-harvested wild-type V. cholerae. At the onset of diarrhea, or at 48 hours after challenge, whichever occurred first, participants received oral iOWH032 500 mg tablets every 8 hours for 3 days. Participants received a 3-day course of antibiotics starting 4 days post-challenge, or sooner if the participant met the criterion for severe cholera diarrhea.

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

47

Start Date

November 4, 2019

Completion Date

July 27, 2020

Primary Completion Date

July 27, 2020

Eligibility Criteria

        Inclusion Criteria:

          1. Willing and able to understand and provide written informed consent

          2. Healthy male and female adults, age 18 to 44 years (inclusive), without clinically
             significant medical history, physical or clinical laboratory abnormalities (as per
             protocol-defined acceptable ranges), and protocol-defined abnormal electrocardiogram
             results at screening

          3. All women must have a negative serum pregnancy test at screening and one day prior to
             challenge.

          4. Agreement by participants to use an adequate method of contraception* during the study
             and for 4 weeks before and after the challenge.

          5. Able to pass a written examination (comprehension assessment test) with a score of ≥
             70%, in order to demonstrate their comprehension of this study. If a participant
             scores at least 50%, then they will be given one more opportunity to re-test after
             further re-education.

          6. Willing and able to comply with the study requirements and procedures.

               -  Adequate contraception is defined as a contraceptive method with failure rate of
                  less than 1% per year when used consistently and correctly and when applicable,
                  in accordance with the product label; includes, but is not limited to, barrier
                  with additional spermicidal foam or jelly, intrauterine device, hormonal
                  contraception (started at least 4 weeks prior to study enrollment), or women who
                  have intercourse limited to men who underwent vasectomy.

        Exclusion Criteria:

          1. Clinically significant history of immunodeficiency, cardiovascular disease,
             respiratory disease, endocrine disorder, liver disease, renal disease,
             gastrointestinal disease, anal or rectal disorders, neurologic disease,

          2. Current nicotine use or drug, alcohol abuse within the past 6 months

          3. Recipient of bone marrow or solid organ transplant

          4. Use of systemic chemotherapy in the past 5 years

          5. Has a malignancy (excluding localized non-melanoma skin cancers) or
             lymphoproliferative disorders diagnosed or treated within the past 5 years

          6. Received or plans to receive systemic immunosuppressive therapy, radiation therapy,
             parenteral or high-dosage inhaled steroids (> 800 µg/day of beclomethasone
             dipropionate or equivalent) within 6 months prior to the enrollment through 28 days
             after challenge

          7. Have a history of hospitalization for psychiatric illness, suicide attempt, or
             confinement for danger to self or others, within the past 10 years. Participants with
             a psychiatric disorder (not meeting exclusion criteria, e.g., attention-deficit
             hyperactivity disorder) that is controlled for a minimum of 3 months and the
             investigator has determined that the participant's mental status will not compromise
             the participant's ability to comply with protocol requirements may be enrolled

          8. Have an elevated blood pressure, systolic ≥ 150 mmHg or diastolic ≥ 90 mmHg, before
             challenge

          9. Taking any of the the protocol-defined drugs that are metabolized by CYP2C9 or any of
             the following psychiatric medications: aripiprazole, carbamazepine, chlorpromazine,
             chlorprothixene, clozapine, divalproex sodium, fluphenazine, haloperidol, lithium
             carbonate, lithium citrate, loxapine, mesoridazine, molindone, olanzapine,
             perphenazine, pimozide, quetiapine, risperidone, thioridazine, thiothixene,
             trifluoperazine, triflupromazine, or ziprasidone

         10. History of Guillain-Barré Syndrome

         11. Too low or too high a body mass index (BMI < 18.5 or > 39)

         12. Has an abnormal stool pattern defined as fewer than 3 stools per week or more than 2
             stools per day within the past 6 months, and any loose stools (grade 3 or higher)
             during the 1-2 day acclimation period before challenge

         13. Has regularly used laxatives in the past 6 months

         14. Has a history of eating disorders (e.g. anorexia or bulimia) within the past 10 years

         15. Known allergy or previous severe adverse effect to all of the following antibiotics:
             ciprofloxacin (or quinolones), azithromycin and doxycycline.

         16. Previously received a licensed or investigational cholera vaccine, within 10 years

         17. History of cholera or enterotoxigenic Escherichia coli (ETEC) infection (lab-confirmed
             natural infection or experimental challenge), within 10 years

         18. Travel to a cholera-endemic area in the past 5 years

         19. Pregnant or nursing

         20. Positive serology for human immunodeficiency virus (HIV), hepatitis B antigen, or
             hepatitis C antibody

         21. Protocol-defined clinically abnormal 12-lead electrocardiogram (ECG) at screening in
             the judgment of the Investigator, or based on the formal 12-lead ECG reading by a
             cardiologist; history of any cardiac abnormalities, including conduction abnormalities
             such as Wolff-Parkinson-White, dysrhythmias, or coronary artery disease

         22. Presence of a clinically significant abnormality on physical examination, including
             (but not limited to): pathologic heart murmur, lymphadenopathy, hepatosplenomegaly,
             large abdominal scar of unclear origin

         23. Has poor venous access, defined as the inability to obtain screening blood tests after
             three attempts

         24. Currently on, or plans to be on, antibiotics (e.g., doxycycline) within 14 days prior
             to challenge and through 28 days after challenge

         25. Presence of an acute illness or fever (> 100.4°F) within 72 hours of admission to the
             inpatient Clinical Research Unit

         26. Taking any prescription or over-the-counter medications that contain aspirin,
             non-steroidal anti-inflammatory drugs (NSAIDs), antacids, proton pump inhibitors
             (PPIs), anti-diarrheals, etc. within 72 hours prior to challenge

         27. Received an investigational product within 30 days prior to randomization (90 days
             prior to randomization for monoclonal antibodies) or planned to participate in another
             research study involving an investigational product during the conduct of this study

         28. Participants must not have donated blood in 8 weeks prior to study entry and agreed to
             not donate blood during and for 4 weeks following their active participation in this
             study

         29. Lack of ability to fully understand the informed consent

         30. Any other condition(s) that in the opinion of the investigator would jeopardize the
             safety or rights of a participant participating in the trial or would render the
             participant unable to comply with the protocol
      

Gender

All

Ages

18 Years - 44 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04150250

Organization ID

DRG-032-PO-2-01-USA


Responsible Party

Sponsor

Study Sponsor

PATH

Collaborators

 University of Maryland, Baltimore

Study Sponsor

, , 


Verification Date

February 2021