Zoliflodacin in Uncomplicated Gonorrhoea

Phase 3

Completed

• Conditions: Gonorrhea
• Interventions: Drug: zoliflodacin; Drug: ceftriaxone; Drug: azithromycin

• Registration Number: NCT03959527
• Lead Sponsor: Global Antibiotics Research and Development Partnership

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-05-02
• Study First Submitted QC: 2019-05-20
• Study First Posted: 2019-05-22
• Study Start: 2019-11-06
• Primary Completion: 2023-08-30
• Study Completion: 2023-09-18
• Results First Submitted: 2024-06-28
• Status Verified: 2024-07
• Results First Submitted QC: 2024-07-25
• Last Update Submitted: 2024-07-25
• Results First Posted: 2024-07-26
• Last Update Posted: 2024-07-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1011

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
zoliflodacin	zoliflodacin	Participant in this arm will receive a single dose of zoliflodacin.
ceftriaxone and azithromycin combination	ceftriaxone	Participant in this arm will receive a single dose of comparators combination (ceftriaxone and azithromycin).
ceftriaxone and azithromycin combination	azithromycin	Participant in this arm will receive a single dose of comparators combination (ceftriaxone and azithromycin).

Primary Outcome Measures

Name	Time	Method
Microbiological Cure Rate for Zoliflodacin Compared to a Combination of a Single Dose of Ceftriaxone and Azithromycin.	Day 6 (+/- 2)	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

Secondary Outcome Measures

Name	Time	Method
Microbiological Cure Rate of Urogenital Gonorrhoea Among Women, After Administration of a Single, Oral, 3 g Dose of Zoliflodacin Compared to a Combination of a Single IM 500 mg Dose of Ceftriaxone and a Single 1 g Oral Dose of Azithromycin	Day 6	Proportion of female participants with microbiological cure as determined by culture at cervical or urethral site at TOC in micro-ITT (Urogenital) population
Microbiological Cure Rate of Rectal Gonorrhoea Will be Determined After Administration of a Single Dose of Zoliflodacin Compared to a Combination of a Single Dose of Ceftriaxone and Azithromycin.	Day 6	Proportion of participants with microbiological cure as determined by culture at rectal sites at test of cure visit in micro-ITT (Rectal).
Proportion of Participants With Eradication of NG NAAT at TOC Determined From Pharyngeal Specimens After Administration of a Single Dose of Zoliflodacin Compared to a Combination of a Single Dose of Ceftriaxone and Azithromycin.	Day 6	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.
Proportion of Participants With Eradication of NG NAAT at TOC Determined From Rectal Specimens After Administration of a Single Dose of Zoliflodacin Compared to a Combination of a Single Dose of Ceftriaxone and Azithromycin.	Day 6	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.
Microbiological Cure Rate of Urogenital Gonorrhoea Among Men, After Administration of a Single, Oral, 3 g Dose of Zoliflodacin Compared to a Combination of a Single IM 500 mg Dose of Ceftriaxone and a Single 1 g Oral Dose of Azithromycin	Day 6	Proportion of male participants with microbiological cure as determined by culture at urethral site at TOC in micro-ITT population
Arithmetic Mean Plasma Concentration of Zoliflodacin	24 - 36 h	Arithmetic mean plasma concentration (ng/mL) of zoliflodacin following administration of a single oral dose of zoliflodacin 3 g
Evaluation of the Plasma PK Profile After a Single, Oral, 3 g Dose of Zoliflodacin	Day 2	Geometric mean plasma area under the concentration-time curve (AUC0-last) from time zero to the last concentration above lower level of quantification
Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin.	Day 30	Incidence, severity, causality and seriousness of treatment-emergent adverse events (including clinically significant abnormal laboratory values/procedures i.e., physical examination per protocol)
Microbiological Cure Rate of Pharyngeal Gonorrhoea Will be Determined After Administration of a Single Dose of Zoliflodacin Compared to a Combination of a Single Dose of Ceftriaxone and Azithromycin.	Day 6	Proportion of participants with microbiological cure as determined by culture at pharyngeal sites at test of cure visit in micro-ITT (Pharyngeal).
The Clinical Cure Rate of Symptomatic Gonorrhoea in Male Participants Will be Determined After Administration of a Single Dose of Zoliflodacin Compared to a Combination of Single Dose of Ceftriaxone and Azithromycin.	Day 6	Proportion of male participants with clinical cure at test of cure visit in Clinical Cure Population.
Antimicrobial Susceptibility Profile Will be Determined of Gonococcal Strains Isolated From Participants With Uncomplicated Gonorrhoea at Baseline and the Test of Cure Visit.	Day 6	Antimicrobial susceptibility profile of gonococcal strains isolated at baseline and at test of cure visit.
The Proportion of Participants With Eradication of NG NAAT at TOC Will be Determined From Urogenital Specimens After Administration of a Single Dose of Zoliflodacin Compared to a Combination of a Single Dose of Ceftriaxone and Azithromycin.	Day 6	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.

Trial Locations

Locations (17)

Public Health - Seattle & King County STD Clinic; 🇺🇸 Seattle, Washington, United States

Jefferson County Department of Health; 🇺🇸 Birmingham, Alabama, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

San Francisco Department Of Public Health City Clinic; 🇺🇸 San Francisco, California, United States

Bell Flower Clinic; 🇺🇸 Indianapolis, Indiana, United States

Institute of Tropical Medicine; 🇧🇪 Antwerp, Belgium

Louisiana State University Health Sciences Center; 🇺🇸 New Orleans, Louisiana, United States

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

Ndlovu Research Centre; 🇿🇦 Elandsdoorn, South Africa

SAMRC Tongaat Clinical Research Site; 🇿🇦 Tongaat, South Africa

Wits RHI; 🇿🇦 Johannesburg, South Africa

Setshaba Research Centre; 🇿🇦 Soshanguve, South Africa

Bangrak STI Center; 🇹🇭 Bangkok, Thailand

Silom Community Clinic; 🇹🇭 Bangkok, Thailand

Institute of HIV Research and Innovation; 🇹🇭 Bangkok, Thailand