Zoliflodacin in Uncomplicated Gonorrhoea

NCT03959527 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: STI_Zoli0012019-000990-22
• Study Type: interventional
• Target: 1,011
• Locations: 5 countries
• Sites: 17

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.

Conditions

Gonorrhea

Outcome Measures

Primary Outcomes (1)

• 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

  Day 6 (+/- 2)

Secondary Outcomes (34)

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

  Day 30

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

  Day 6

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

  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.

  Day 6

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

  Day 6

Study Arms (2)

zoliflodacin

EXPERIMENTAL

Participant in this arm will receive a single dose of zoliflodacin.

Drug: zoliflodacin

ceftriaxone and azithromycin combination

ACTIVE COMPARATOR

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

Drug: ceftriaxone; Drug: azithromycin

Interventions

zoliflodacin DRUG

Dose: 3g, oral administration

zoliflodacin

ceftriaxone DRUG

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

ceftriaxone and azithromycin combination

azithromycin DRUG

Dose: 1g, oral administration

ceftriaxone and azithromycin combination

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 12 years old (if enrolment of minors is in agreement with local regulations and Ethics guidance)
• Weight ≥ 35 kg
• 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)
• For females of child-bearing potential, a negative urine pregnancy test at screening
• 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.
• For males with a female partner of child-bearing age, willingness to delay conception for 28 days after treatment
• Willingness to comply with trial protocol
• Willingness to undergo HIV testing
• Willingness to abstain from sexual intercourse or use condoms for vaginal, anal and oral sex until end of trial visit
• 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).

You may not qualify if:

• Confirmed or suspected complicated or disseminated gonorrhoea
• Pregnant or breastfeeding women
• Known concomitant infection which would require immediate additional systemic antibiotics with activity against NG (e.g. CT infection)
• Use of any systemic or intravaginal antibiotics with activity against NG within 30 days prior to screening
• Use of systemic corticoid drugs or other immunosuppressive therapy within 30 days prior to screening
• 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
• Cytotoxic or radiation therapy within 30 days prior to screening
• 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
• History of urogenital sex-reassignment surgery
• Immunosuppression as evidenced by medical history, clinical examination or a recent (≤ 1 month) CD4 count \<200 cells/μL
• Know clinically relevant cardiac pro-arrhythmic conditions such as cardiac arrhythmia, congenital or documented QT prolongation
• Known history of severe allergy to cephalosporin, penicillin, monobactams, carbapenems or macrolide antibiotics
• 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)
• 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
• History of alcohol or drug abuse within 12 months prior to screening which would compromise trial participation in the judgment of the investigator

Sponsors & Collaborators

• Global Antibiotics Research and Development Partnership: lead

Study Sites (17)

Jefferson County Department of Health

Birmingham, Alabama, 35233, United States

Location

University of Alabama at Birmingham

Birmingham, Alabama, 35294-0006, United States

Location

San Francisco Department Of Public Health City Clinic

San Francisco, California, 94103, United States

Location

Bell Flower Clinic

Indianapolis, Indiana, 46202, United States

Location

Louisiana State University Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

Public Health - Seattle & King County STD Clinic

Seattle, Washington, 98104, United States

Location

Institute of Tropical Medicine

Antwerp, 2000, Belgium

Location

Public Health Service (GGD) Amsterdam / STI Outpatient Clinic

Amsterdam, 1018 WT, Netherlands

Location

SAMRC Botha's Hill Clinical Research Site

Bothas Hill, 3660, South Africa

Location

Masiphumelele Research Site

Cape Town, 7975, South Africa

Location

Ndlovu Research Centre

Elandsdoorn, 0470, South Africa

Location

Wits RHI

Johannesburg, 2001, South Africa

Location

Setshaba Research Centre

Soshanguve, 0152, South Africa

Location

SAMRC Tongaat Clinical Research Site

Tongaat, 4400, South Africa

Location

Bangrak STI Center

Bangkok, 10120, Thailand

Location

Institute of HIV Research and Innovation

Bangkok, 10330, Thailand

Location

Silom Community Clinic

Bangkok, 10400, Thailand

Location

Related Publications (2)

• Luckey A, Balasegaram M, Barbee LA, Batteiger TA, Broadhurst H, Cohen SE, Delany-Moretlwe S, de Vries HJC, Dionne JA, Gill K, Kenyon C, Kittiyaowamarn R, Lewis D, Mueller JP, Naicker V, O'Brien S, O'Donnell JP, Phanuphak N, Spooner E, Srinivasan S, Taylor SN, Unemo M, Zwane Z, Hook EW 3rd; Zoliflodacin Phase 3 Study Group. Zoliflodacin versus ceftriaxone plus azithromycin for treatment of uncomplicated urogenital gonorrhoea: an international, randomised, controlled, open-label, phase 3, non-inferiority clinical trial. Lancet. 2026 Jan 10;407(10524):147-160. doi: 10.1016/S0140-6736(25)01953-1. Epub 2025 Dec 11.

  PMID: 41391465 DERIVED

• Jacobsson S, Golparian D, Oxelbark J, Kong FYS, Da Costa RMA, Franceschi F, Brown D, Louie A, Drusano G, Unemo M. Pharmacodynamics of zoliflodacin plus doxycycline combination therapy against Neisseria gonorrhoeae in a gonococcal hollow-fiber infection model. Front Pharmacol. 2023 Dec 7;14:1291885. doi: 10.3389/fphar.2023.1291885. eCollection 2023.

  PMID: 38130409 DERIVED

MeSH Terms

Conditions

Gonorrhea

Interventions

zoliflodacin; Ceftriaxone; Azithromycin

Condition Hierarchy (Ancestors)

Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sexually Transmitted Diseases, Bacterial; Sexually Transmitted Diseases; Communicable Diseases; Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones

Limitations and Caveats

Relatively low representation of females in primary analysis set due to asymptomatic nature of NG in this population, non-specific symptoms and inclusion criteria (prior contraceptive use). Relatively low representation of adolescents in study and non in PK sub-study, due to challenges with obtaining parental consent primarily in this indication.

Results Point of Contact

• Title: Dr Alison Luckey
• Organization: GARDP

aluckey@gardp.org

+41 22 559 05 39

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single dose of Zoliflodacin or comparators combination in single dose: ceftriaxone and azithromycin

Study Record Dates

• First Submitted: May 2, 2019
• First Posted: May 22, 2019
• Study Start: November 6, 2019
• Primary Completion: August 30, 2023
• Study Completion: September 18, 2023
• Last Updated: October 8, 2025
• Results First Posted: July 26, 2024

Record last verified: 2025-09

Locations

BE (1); TH (3); NL (1); US (6); ZA (6)