Zoliflodacin in Uncomplicated Gonorrhoea

Global Antibiotics Research and Development Partnership1,011 enrolled

Overview

This trial is a multi-center, open label, randomized controlled, non-inferiority phase III trial evaluating the safety and efficacy of a 3 g oral dose of zoliflodacin compared to a combination of a single intra-muscular 500 mg dose of ceftriaxone and a single 1 g oral dose of azithromycin for the treatment of uncomplicated gonorrhoea.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

1,011

Conditions

Gonorrhea

Interventions

zoliflodacinDRUG

Dose: 3g, oral administration

ceftriaxoneDRUG

Dose: 500mg, Intra-Muscular (IM) administration

azithromycinDRUG

Dose: 1g, oral administration

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥ 12 years old (if enrolment of minors is in agreement with local regulations and Ethics guidance) 2. Weight ≥ 35 kg 3. Signs and symptoms consistent with urethral or cervical gonorrhoea OR Urethral or cervical uncomplicated gonorrhoea as determined by either a positive culture or NAAT or Gram stain or methylene blue test/gentian violet stain in the past 14 days prior to screening OR Unprotected sexual contact with an individual reported to be infected with NG in the past 14 days prior to screening (confirmation by a positive NAAT, Gram stain or methylene blue test/ gentian violet stain or culture) 4. For females of child-bearing potential, a negative urine pregnancy test at screening 5. For females of child bearing potential, use of highly effective contraception for at least 28 days prior to screening and during at least 28 days after treatment. Females on oral contraceptives must also use a barrier contraception method during participation in the study. 6. For males with a female partner of child-bearing age, willingness to delay conception for 28 days after treatment 7. Willingness to comply with trial protocol 8. Willingness to undergo HIV testing 9. Willingness to abstain from sexual intercourse or use condoms for vaginal, anal and oral sex until end of trial visit 10. Willingness and ability to give written informed consent or be consented by a legal representative or provide assent and parental consent (for minors, as appropriate). Exclusion Criteria: 11. Confirmed or suspected complicated or disseminated gonorrhoea 12. Pregnant or breastfeeding women 13. Known concomitant infection which would require immediate additional systemic antibiotics with activity against NG (e.g. CT infection) 14. Use of any systemic or intravaginal antibiotics with activity against NG within 30 days prior to screening 15. Use of systemic corticoid drugs or other immunosuppressive therapy within 30 days prior to screening 16. Use of moderate or strong CYP3A4 inducers (e.g. efavirenz, rifampicin, carbamazepine, phenobarbital) within 30 days or five half-lives of the drug, whichever is greater, prior to screening 17. Cytotoxic or radiation therapy within 30 days prior to screening 18. Known chronic renal, hepatic, hematologic impairment or other condition interfering with the absorption, distribution or elimination of the drug based on medical history and physical examination 19. History of urogenital sex-reassignment surgery 20. Immunosuppression as evidenced by medical history, clinical examination or a recent (≤ 1 month) CD4 count \<200 cells/μL 21. Know clinically relevant cardiac pro-arrhythmic conditions such as cardiac arrhythmia, congenital or documented QT prolongation 22. Known history of severe allergy to cephalosporin, penicillin, monobactams, carbapenems or macrolide antibiotics 23. Known or suspected allergies or hypersensitivities to lidocaine, methylparaben, lactose or any of the components of the study drugs (refer to the zoliflodacin IB and SmPC for the comparators treatments) 24. Receipt or planned receipt of an investigational product in a clinical trial within 30 days or five half-lives of the drug, whichever is greater, prior to screening until end of participation to this clinical trial 25. History of alcohol or drug abuse within 12 months prior to screening which would compromise trial participation in the judgment of the investigator 26. Severe medical or psychiatric condition which, in the opinion of the investigator, may increase the risk associated with trial participation or may interfere with the interpretation of trial results or affect the individual's ability to provide informed consent 27. Individuals whom, in the judgement of the investigator, are unlikely or unable to comply with this trial protocol 28. Previous randomisation in this clinical trial. 29. Use of moderate or strong CYP3A4 inhibitors within 30 days or five half-lives of the drug, whichever is greater, prior to screening

Locations (17)

Jefferson County Department of Health

Birmingham, Alabama, United States

University of Alabama at Birmingham

Birmingham, Alabama, United States

Outcomes

Primary Outcomes

Microbiological Cure Rate for Zoliflodacin Compared to a Combination of a Single Dose of Ceftriaxone and Azithromycin.

Proportion of participants with microbiological cure as determined by culture at urethral or cervical sites at test of cure visit in micro-ITT (urogenital) analysis set

Time frame: Day 6 (+/- 2)

Secondary Outcomes

Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin.

Incidence, severity, causality and seriousness of treatment-emergent adverse events (including clinically significant abnormal laboratory values/procedures i.e., physical examination per protocol)

Time frame: Day 30

Microbiological Cure Rate of Pharyngeal Gonorrhoea of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin.

Proportion of participants with microbiological cure as determined by NG culture at pharyngeal sites at test of cure visit in micro-ITT (Pharyngeal).

Time frame: Day 6

Microbiological Cure Rate of Rectal Gonorrhoea of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin.

Proportion of participants with microbiological cure as determined by NG culture at rectal sites at test of cure visit in micro-ITT (Rectal).

Time frame: Day 6

The Clinical Cure Rate in Male Participants After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin.

Proportion of male at birth participants experiencing resolution of signs and symptoms of urogenital gonococcal infection that were present at enrolment, at test of cure visit in Clinical Cure Population.

Time frame: Day 6

Data from ClinicalTrials.gov

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San Francisco Department Of Public Health City Clinic

San Francisco, California, United States

Bell Flower Clinic

Indianapolis, Indiana, United States

Louisiana State University Health Sciences Center

New Orleans, Louisiana, United States

Public Health - Seattle & King County STD Clinic

Seattle, Washington, United States

Institute of Tropical Medicine

Antwerp, Belgium

Public Health Service (GGD) Amsterdam / STI Outpatient Clinic

Amsterdam, Netherlands

SAMRC Botha's Hill Clinical Research Site

Bothas Hill, South Africa

Masiphumelele Research Site

Cape Town, South Africa

...and 7 more locations

Microbiological Cure Rate Among Females, After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin

Proportion of female participants with microbiological cure, as determined by NG culture at cervical site of infection, at TOC in micro-ITT (Urogenital) population

Microbiological Cure Rate Among Males, After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin

Proportion of male participants with microbiological cure as determined by NG culture at urethral site of infection at TOC visit, in micro-ITT population

Time frame: Day 6

Eradication of Urogenital NG NAAT at TOC After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin.

Proportion of participants with a positive NG NAAT result from urethral or cervical sites at baseline and a negative NG NAAT result at test of cure visit in micro-ITT analysis set.

Time frame: Day 6

Eradication of Pharyngeal NG NAAT at TOC After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin.

Proportion of participants with a positive NG NAAT at baseline from pharyngeal sites and a negative NG NAAT at test of cure visit in micro-ITT analysis set.

Time frame: Day 6

Eradication of Rectal NG NAAT at TOC After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin.

Proportion of participants with a positive NG NAAT from rectal sites at baseline and a negative NG NAAT at test of cure visit in micro-ITT analysis set.

Time frame: Day 6