Zoliflodacin in Uncomplicated Gonorrhoea

Gonorrhea Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03959527
• Other study ID #: STI_Zoli001
• Secondary ID: 2019-000990-22
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 6, 2019
• Est. completion date: December 10, 2023

Study information

• Verified date: May 2023
• Source: Global Antibiotics Research and Development Partnership
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1092
• Est. completion date: December 10, 2023
• Est. primary completion date: August 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Gonorrhea

Intervention

Drug:
• zoliflodacin
Dose: 3g, oral administration
• ceftriaxone
Dose: 500mg, Intra-Muscular (IM) administration
• azithromycin
Dose: 1g, oral administration

Locations

Country	Name	City	State
Belgium	Institute of Tropical Medicine	Antwerp
Netherlands	Public Health Service (GGD) Amsterdam / STI Outpatient Clinic	Amsterdam
South Africa	SAMRC Botha's Hill Clinical Research Site	Bothas Hill
South Africa	Masiphumelele Research Site	Cape Town
South Africa	Ndlovu Research Centre	Elandsdoorn
South Africa	Wits RHI	Johannesburg
South Africa	Setshaba Research Centre	Soshanguve
South Africa	SAMRC Tongaat Clinical Research Site	Tongaat
Thailand	Bangrak STI Center	Bangkok
Thailand	Institute of HIV Research and Innovation	Bangkok
Thailand	Silom Community Clinic	Bangkok
United States	Jefferson County Department of Health	Birmingham	Alabama
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Bell Flower Clinic	Indianapolis	Indiana
United States	Louisiana State University Health Sciences Center	New Orleans	Louisiana
United States	San Francisco Department Of Public Health City Clinic	San Francisco	California
United States	Public Health - Seattle & King County STD Clinic	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Global Antibiotics Research and Development Partnership

Countries where clinical trial is conducted

United States,  Belgium,  Netherlands,  South Africa,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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