Repurposing Clinically Approved Drugs for Yaws with an Insight Into the Cutaneous Ulcer Disease Syndrome (Trep-AByaws)

NCT05764876 | Completed Phase 3 DMC

• 1 other identifier: Trep-AByaws
• Study Type: interventional
• Target: 465
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to test the non inferiority of linezolid compared with azithromycin as a treatment for yaws . The main questions it aims to answer are: can linezolid cure active yaws, and can linezolid cure latent yaws. Participants with serologically confirmed yaws will be randomized to receive linezolid (experimental) or azithromycin (control group) treatment and followed up to assess clinical resolution.

Conditions

Yaws; Cutaneous Ulcer

Keywords

azithromycin; linezolid

Outcome Measures

Primary Outcomes (5)

• Clinical resolution

  Proportion of patients with clinical resolution of yaws lesions (clinical cure). Assessment of clinical resolution defined as the complete healing of lesions at 4 weeks from treatment start.

  4 weeks after treatment

• Serological cure

  Proportion of patients with adequate serological response (serological cure). Assessment of sero-cure is described as a four-fold decline in rapid plasma reagin (RPR) titer or seroreversion at 24 weeks from treatment start.

  24 weeks after treatment

• Serological cure

  Proportion of patients with adequate serological response (serological cure). Assessment of sero-cure is described as a four-fold decline in rapid plasma reagin (RPR) titer or seroreversion at 48 weeks from treatment start.

  48 weeks after treatment

• Relapse

  Proportion of patients with relapse (recurrent episodes caused by the same strain) (molecular cure). Assessment of recurrence by molecular methods of Treponema pallidum ssp. pertenue (TPE) DNA in ulcer swab to determine relapse or reinfection within 24 weeks from treatment start.

  24 weeks after treatment

• Relapse

  Proportion of patients with relapse (recurrent episodes caused by the same strain) (molecular cure). Assessment of recurrence by molecular methods of Treponema pallidum ssp. pertenue (TPE) DNA in ulcer swab to determine relapse or reinfection within 48 weeks from treatment start.

  48 weeks after treatment

Secondary Outcomes (7)

• Lession (ulcer swab) TPE assessment

  Baseline (before treatment)

• Oral (oral swab) TPE assessment

  Baseline (before treatment)

• Plasma TPE assessment

  Baseline (before treatment)

• Allelic variation in recurrent cases

  Baseline (before treatment)

• Identification of antibiotic resistance genotype.

  4 weeks after treatment

Study Arms (2)

Azithromycin

ACTIVE COMPARATOR

Participants in the control arm will receive standard treatment for yaws which azithromycin .

Drug: Azithromycin Oral Tablet

Linezolid

EXPERIMENTAL

Participants in the experimental arm will receive oral linezolid treatment.

Drug: Linezolid Oral Tablet

Interventions

Linezolid Oral Tablet DRUG

Oral tablet of linezolid 10mg/kg every 8 hours for 7 days.

Also known as: Zyvox, Zyvoxid

Linezolid

Azithromycin Oral Tablet DRUG

Oral tablet of azithromycin 30mg/kg maximum 2gr single dose.

Also known as: Zithromax

Azithromycin

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participants 5-18 years identified during an active case search program at the elementary, primary and secondary schools in the Islands Region.
• CUD syndrome suspected due to yaws: one or more ulcerative or nodular or papilloma skin lesion of more than 1 cm in diameter.
• Positive treponemal (T1) and non-treponemal (T2) serology by Chembio dual path platform (DPP) syphilis screen \& confirm assay (DPP test).
• Accepted and signed informed consent.
• Ability to comply with the requirements of the study protocol including follow up visits.

You may not qualify if:

• Children younger than 5 years old.
• Clinical late-stage possible yaws: destructive osteitis (rhinopharyngitis gangosa, sabre shins) or gummous nodules.
• Known allergy to LZD or AZI antibiotics.
• Pregnant or breastfeeding women.
• Have taken any antibiotics with potential activity against TPE within the last 7 days prior to randomization (i.e., beta lactams, cephalosporines, macrolides, tetracyclines).
• Uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, carcinoid syndrome, bipolar disorder, incapacitating psycho-affective disturbance, acute confusional state.
• Renal function impairment requiring hemodialysis.
• Current treatment with any drugs likely to interact with the study medication
• Symptomatic concomitant infection requiring antibiotic treatment potentially active against TPE.
• Having received treatment for yaws in the last 6 months.
• Patients who are unable to take oral medication or having a gastrointestinal disease likely to interfere with drug absorption (including malnutrition and stomach flu).

Sponsors & Collaborators

• Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia: lead
• National Department of Health, Papua New Guinea: collaborator
• School of Medicine and Health Sciences, University of Papua New Guinea: collaborator

Study Sites (1)

National Department of Health

Port Moresby, Papua New Guinea

Location

MeSH Terms

Conditions

Yaws; Skin Ulcer

Interventions

Linezolid; Azithromycin

Condition Hierarchy (Ancestors)

Treponemal Infections; Spirochaetales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Skin Diseases, Bacterial; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones

Study Officials

• Camila Beiras

  Fundació Lluita contra les Infeccions

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: Investigator will not be present for treatment nor for outcome assessment, and data analysis (statistics) will be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Infectious Diseases and Global Health

Model Details: Open-label, non inferiority, two arms and randomized clinical trial. Eligible patients will be randomized (1:1) to receive Linezolid (experimental arm) or Azithromycin (control arm).

Study Record Dates

• First Submitted: February 2, 2023
• First Posted: March 13, 2023
• Study Start: March 14, 2023
• Primary Completion: June 20, 2024
• Study Completion: December 1, 2024
• Last Updated: January 9, 2025

Record last verified: 2024-07

Locations

PA (1)