Assessment of a Novel Fixed-dose Combination (FDC) Drug VR-AD-1005 for the Treatment of Acute Watery Diarrhea in Cholera

Assessment of a Novel Fixed-dose Combination (FDC) Drug VR-AD-1005 for the Treatment of Acute Watery Diarrhea in Cholera: a Phase II, Randomized, Placebo-controlled, Double-blinded Efficacy and Safety Trial

Cholera still remains a global public health concern affecting both children and adults, and patients can succumb in quick time if remain untreated. Cholera is a secretory diarrhea and is generally treated with oral or intravenous rehydration therapy to compensate for the fluid loss. However, antimicrobial treatment is given to patients with moderate to severe diarrhea. The consistent emergence of multidrug-resistant bacteria is a major concern for the management of infectious diseases including cholera. No antisecretory drug has so far been proven successful. In a phase II clinical trial, the investigators will assess the effectiveness of a novel antisecretory drug VR-AD-1005 for treating cholera. Changes in stool volume and rehydration therapy will be assessed for VR-AD-1005 in comparison with placebo. If successful, this will be a huge advance in managing cholera and other secretory diarrhea. The introduction of the antisecretory drug can minimize the hospital stay and reduce antibiotic use, which in turn can reduce the emergence of antibiotic resistance among pathogens

Study Overview

• Status: Recruiting
• Conditions: Cholera
• Intervention / Treatment: Drug: Placebo; Drug: VR-AD-1005

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dmitry V Kravtsov, MD; Phone Number: +1 203 836 8424 x 114; Email: dmitry.kravtsov@hunazinebiotech.com

Study Locations

• Bangladesh
  • Dhaka, Bangladesh
    • Recruiting
    • Icddr,b
    • Contact: Icddr,b

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Signed informed consent.
• Adults, both genders aged 18-65 years.
• Acute watery diarrhea (defined as passage of three or more liquid stools within the 24 hours before admission) with severe dehydration on arrival.
• Detection of V. cholerae by rapid diagnostic assay (e.g. dark field microscopy).

Exclusion Criteria:

• Known or suspected hypersensitivity to trial product(s) or related products.
• Subjects with passage of bloody stools or muco-purulent stools.
• Subjects with chronic diarrhea (>4 weeks of Diarrhea).
• Clinically significant concomitant systemic disease (i.e. cardiovascular diseases including heart failure, acute kidney injury, sepsis or life-threatening malignant cancer).
• Mental incapacity, unwillingness, or language barriers, precluding adequate understanding or cooperation.
• History of receiving antimicrobial or antidiarrheal drugs within 6 hours prior to admission.
• Positive urine pregnancy test for all female patients
• Failure to obtain informed consent.
• Failure to definitively diagnose cholera via culture or RT-PCR

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; oral capsule
Experimental: VR-AD-1005	Drug: VR-AD-1005; oral capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in stool output volume during treatment period.	Change in stool output volume (ml/hour) over a treatment period measured and plotted as total stool output during 12-hour stool collection at every 12 hours for 72 hours	3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time until the stool volume output of 200 ml/hour	time (hours) from start of treatment until the stool output changes (reduces) to 200 ml/hour or less	3 days
Number of subjects with clinical recovery	Total number of subjects achieving clinical recovery during treatment period expressed as a fraction of the total subjects per treatment arm.	3 days
Number of unscheduled IV rehydration episodes per treatment	Average number of unscheduled IV rehydration episodes per participant per treatment arm.	3 days
Duration of IV rehydration	Average duration of IV rehydration per subject per treatment arm expressed in hours.	3 days
Adverse Events Occurrence	Average number of adverse events per subject per treatment arm	28 days

Collaborators and Investigators

• Sponsor: Hunazine Biotech S.L.

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2024
• Primary Completion (Estimated): May 15, 2024
• Study Completion (Estimated): June 15, 2024

Study Registration Dates

• First Submitted: December 12, 2023
• First Submitted That Met QC Criteria: December 21, 2023
• First Posted (Actual): January 5, 2024

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Signs and Symptoms, Digestive; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Vibrio Infections; Diarrhea; Cholera
• Other Study ID Numbers: PR-23089

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No