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

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

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh
    • Icddr,B

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

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
Stool Output Volume During Treatment Period.	Means of stool output data expressed as ml/kg·h-1 for Treatment and Comparator groups.	Stool output volume was measured and recorded hourly for each participant for the entire duration of treatment (from enrollment up to 72 hours, e.g. hour 1, hour 6, hour 8, hour 10, hour 11, hour 22, hour 23, hour 26, etc.).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Stool Output in Excess of 200 ml/Hour	For analysis, individual stool charts were used to calculate stool output per patient per hour and express it as stool volume in ml/hour. Duration of time during treatment when stool output was in excess of 200ml/hour was calculated for each participant and compared for control and study intervention groups.	Stool output volume was measured and recorded hourly for each participant for the entire duration of treatment (from enrollment up to 72 hours).
Number of Unscheduled IV Rehydration Episodes Per Treatment	Average number of unscheduled IV rehydration episodes per participant per study arm.	Unscheduled IV rehydration episodes were measured and recorded hourly for each participant for the entire duration of treatment (from enrollment up to 72 hours).
Volume of IV Rehydration, ml/kg	Average volume of IV rehydration per subject per treatment arm was calculated as aggregate per time period. Data were analyzed for three time periods, namely 0-12 hours; 0-24 hours; and the entire duration of treatment. For each period, mean volume of the infusion was calculated and expressed in ml/kg body weight.	Volume of administered IV rehydration solution was measured and recorded hourly for each participant for the entire duration of treatment (from enrollment up to 72 hours).
Time Until Last Liquid Stool	Diarrhea duration is measured from the first dose of study drug to resolution. Time (hours) from start of treatment until the last liquid stool was determined for each participant. Data were extracted from individual stool charts, and time-to-criterion was analyzed using log-rank statistics between the Treatment and the Comparator groups.	Liquid and solid stool output was measured by trained trial personnel and recorded hourly for each participant for the entire duration of treatment (from enrollment up to 72 hours).
Duration of Stool Output in Excess of 400 mL/Hour	For analysis, individual stool charts were used to calculate stool output per patient per hour and express it as stool volume in ml/hour. Duration of time during treatment when stool output was in excess of 400ml/hour was calculated for each participant and compared for control and study intervention groups.	Stool output volume was measured and recorded hourly for each participant for the entire duration of treatment (from enrollment up to 72 hours).
Participants With at Least One Adverse Event	Proportion of participants experiencing at least one adverse event (including serious adverse events) following administration of study treatment during the safety evaluation period.	From enrollment until the end of follow-up, up to 28 days

Collaborators and Investigators

• Sponsor: Hunazine Biotech S.L.

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2024
• Primary Completion (Actual): August 11, 2024
• Study Completion (Actual): September 8, 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 (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Vibrio Infections; 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
• product manufactured in and exported from the U.S.: No