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
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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
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Verification Date
February 2021