Zoliflodacin in Uncomplicated Gonorrhoea

A Multi-center, Randomized, Open-label, Non Inferiority Trial to Evaluate the Efficacy and Safety of a Single, Oral Dose of Zoliflodacin Compared to a Combination of a Single Intramuscular Dose of Ceftriaxone and a Single Oral Dose of Azithromycin in the Treatment of Patients With Uncomplicated Gonorrhoea

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 Overview

• Status: Active, not recruiting
• Conditions: Gonorrhea
• Intervention / Treatment: Drug: zoliflodacin; Drug: ceftriaxone; Drug: azithromycin

• Study Type: Interventional
• Enrollment (Actual): 1092
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Cherine Bajjali; Phone Number: +41 (0)22 555 19 90; Email: cbajjali@gardp.org
• Study Contact Backup: Name: Alison Luckey; Phone Number: +41 (0)22 555 19 90; Email: aluckey@gardp.org

Study Locations

• Belgium
  • Antwerp, Belgium, 2000
    • Institute of Tropical Medicine
• Netherlands
  • Amsterdam, Netherlands, 1018 WT
    • Public Health Service (GGD) Amsterdam / STI Outpatient Clinic
• South Africa
  • Bothas Hill, South Africa, 3660
    • SAMRC Botha's Hill Clinical Research Site
  • Cape Town, South Africa, 7975
    • Masiphumelele Research Site
  • Elandsdoorn, South Africa, 0470
    • Ndlovu Research Centre
  • Johannesburg, South Africa, 2001
    • Wits RHI
  • Soshanguve, South Africa, 0152
    • Setshaba Research Centre
  • Tongaat, South Africa, 4400
    • SAMRC Tongaat Clinical Research Site
• Thailand
  • Bangkok, Thailand, 10120
    • Bangrak STI Center
  • Bangkok, Thailand, 10330
    • Institute of HIV Research and Innovation
  • Bangkok, Thailand, 10400
    • Silom Community Clinic
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-0006
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35233
      • Jefferson County Department of Health
  • California
    • San Francisco, California, United States, 94103
      • San Francisco Department Of Public Health City Clinic
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Bell Flower Clinic
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Health Sciences Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Public Health - Seattle & King County STD Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 12 years old (if enrolment of minors is in agreement with local regulations and thics 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: zoliflodacin; Participant in this arm will receive a single dose of zoliflodacin.	Drug: zoliflodacin; Dose: 3g, oral administration
Active Comparator: ceftriaxone and azithromycin combination; Participant in this arm will receive a single dose of comparators combination (ceftriaxone and azithromycin).	Drug: ceftriaxone; Dose: 500mg, Intra-Muscular (IM) administration; Drug: azithromycin; Dose: 1g, oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of a single dose of zoliflodacin will be assessed compared to a combination of a single dose of ceftriaxone and azithromycin.	Microbiological cure as determined by culture at urethral or cervical sites at test of cure visit.	Day 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of a single dose of zoliflodacin will be assessed compared to a combination a single dose of ceftriaxone and azithromycin.	Adverse events will be assessed.	Day 6 and Day 30
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.	Proportion of participants with microbiological cure as determined by culture at pharyngeal sites at test of cure visit.	Day 6
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.	Proportion of participants with microbiological cure as determined by culture at rectal sites at test of cure visit.	Day 6
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.	Proportion of male participants with clinical cure at test of cure visit.	Day 6
Microbiological cure rate of urogenital gonorrhoea will be determined among women and men respectively, after administration of a single dose of zoliflodacin compared to a combination of a single dose of ceftriaxone and azithromycin.	Proportion of female and male participants respectively with microbiological cure as determined by culture at cervical or urethral site at test of cure visit.	Day 6
Microbiological cure rate of Neisseria gonorrhoeae (NG) at urogenital sites will be determined.	Proportion of participants with microbiological cure as determined by culture at urethral or cervical sites at the test of cure visit and for whom the baseline antimicrobial susceptibility profile indicated pre-existing resistance to antibiotics commonly used for Neisseria gonorrhoeae (NG) treatment.	Day 6
Antimicrobial susceptibility profile will be determined of gonococcal strains isolated from participants with uncomplicated gonorrhoea at baseline and the test of cure visit.	Antimicrobial susceptibility profile of gonococcal strains isolated at baseline and at test of cure visit.	Day 6
The eradication rate of NG nucleic acid will be determined from urogenital rectal, pharyngeal specimens after administration of a single dose of zoliflodacin compared to a combination of a single dose of ceftriaxone and azithromycin.	Proportion of participants with a negative NG NAAT from urethral or cervical, oropharyngeal and rectal sites at test of cure visit.	Day 6
The plasma concentration will be evaluated (included Area Under the Curve (AUC) over 36 hours) after a single dose of zoliflodacin.	Five PK timepoints post-treatment will be assessed.	Day 2

Collaborators and Investigators

• Sponsor: Global Antibiotics Research and Development Partnership

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2019
• Primary Completion (Anticipated): August 30, 2023
• Study Completion (Anticipated): December 10, 2023

Study Registration Dates

• First Submitted: May 2, 2019
• First Submitted That Met QC Criteria: May 20, 2019
• First Posted (Actual): May 22, 2019

Study Record Updates

• Last Update Posted (Actual): May 12, 2023
• Last Update Submitted That Met QC Criteria: May 11, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Communicable Diseases; Sexually Transmitted Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neisseriaceae Infections; Sexually Transmitted Diseases, Bacterial; Gonorrhea; Anti-Infective Agents; Anti-Bacterial Agents; Ceftriaxone; Azithromycin
• Other Study ID Numbers: STI_Zoli001; 2019-000990-22 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No