Lefamulin for M. Genitalium Treatment Failures
Primary Purpose
Mycoplasma Genitalium Infection
Status
Suspended
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Lefamulin
Doxycycline
Sponsored by
About this trial
This is an interventional treatment trial for Mycoplasma Genitalium Infection focused on measuring Lefamulin, Doxycycline, M. genitalium
Eligibility Criteria
Inclusion Criteria:
- Physician referral
- Persistent symptomatic urogenital M. genitalium infection documented by any nucleic acid amplification test (NAAT) 14-90 days after completion of the prior antimicrobial regimen for M. genitalium
- Low risk of reinfection, defined as no unprotected sex with an untreated sex partner since completion of the prior antimicrobial regimen for M. genitalium
- Living in the United States
- Male or female sex at birth
- At least 18 years of age
- English-speaking
- Able to provide written informed consent
- Able to undergo a test to confirm M. genitalium infection at baseline and tests of cure 21-28 days and 42-47 days after completion of the lefamulin
- Referring physician willing and able to provide needed patient information
Exclusion Criteria:
- Rectal M. genitalium infection only
- Females with pelvic inflammatory disease (PID), pregnancy, or currently breastfeeding
- Females of reproductive age not on a highly effective method of contraception (i.e., intrauterine device (IUD), Nexplanon, progesterone only depot injection with last injection less than three months prior, oral contraceptive pill and last menstrual period less than 28 days prior)
- Known QT prolongation or ventricular arrhythmias including torsades de pointes
- Receiving concurrent drugs known to prolong QT interval (i.e., Class IA or III antiarrhythmics, antipsychotics, erythromycin, pimozide, moxifloxacin, tricyclic antidepressants)
- Receiving strong or moderate CYP3A or P-gp inducers, strong CYP3A or P-gp inhibitors, moderate CYP3A or P-gp inhibitors, or sensitive CYP3A4 substrates that prolong QT interval
- Moderate or severe liver impairment
- Known liver disease
- Renal failure requiring dialysis
- Known allergy to doxycycline, other tetracyclines, and/or lefamulin
- Unwilling or unable to undergo a test to confirm M. genitalium infection at baseline or tests of cure 21-28 days and 42-47 days after completion of the lefamulin
- Not fluent in English and/or not able to provide written informed consent
- Referring physician unwilling or unable to provide needed patient information
- At the study physician's discretion
Sites / Locations
- University of Washington
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Lefamulin alone
Doxycycline followed by lefamulin
Arm Description
Lefamulin 600mg tablet orally twice daily for 7 days
Doxycycline 100mg tablet orally twice daily for 7 days followed by lefamulin 600mg tablet orally twice daily for 7 days
Outcomes
Primary Outcome Measures
Microbiologic cure
Defined as a negative Aptima Mycoplasma genitalium test 21-28 days after completion of the lefamulin
Secondary Outcome Measures
Microbiologic cure after lefamulin alone compared to microbiologic cure after doxycycline followed by lefamulin
Defined as a negative Aptima Mycoplasma genitalium test 21-28 days after completion of the lefamulin
Clinical cure
Defined as the absence of symptoms, visible discharge, and other clinical signs (e.g., less than 5 PMNs/HPF on Gram stained smear where available) 21-28 days after completion of the lefamulin
Reported adherence to lefamulin
Defined by self-reported number of tablets taken
Reported adverse events
Defined by self-reported adverse events
Sustained microbiologic cure
Defined as a negative Aptima Mycoplasma genitalium test 42-47 days after completion of the lefamulin
Full Information
NCT ID
NCT05111002
First Posted
October 27, 2021
Last Updated
February 10, 2023
Sponsor
University of Washington
Collaborators
Nabriva Therapeutics AG
1. Study Identification
Unique Protocol Identification Number
NCT05111002
Brief Title
Lefamulin for M. Genitalium Treatment Failures
Official Title
Lefamulin for Mycoplasma Genitalium Treatment Failures in the US
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Suspended
Why Stopped
At Sponsor Request
Study Start Date
April 22, 2022 (Actual)
Primary Completion Date
April 22, 2023 (Anticipated)
Study Completion Date
April 22, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
Nabriva Therapeutics AG
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this drug study is to find out whether the antibiotic lefamulin (trade name Xenleta) will cure Mycoplasma genitalium infections that have not been cured by prior antibiotics while finding out whether it is more effective if the antibiotic doxycycline is taken first.
Detailed Description
Study participants will be randomly chosen to receive either lefamulin alone or doxycycline followed by lefamulin in a 1:1 ratio. Each participant will receive 14 lefamulin pills or 14 doxycycline pills and 14 lefamulin pills in the mail and take them as directed for one week (each). Participants will collect one culture sample and one sample to confirm M. genitalium infection on the same day they take their first pill then mail the two samples to the laboratory. They will also answer questions about their symptoms, any side effects, and their behavior with their sex partners. Participants will collect samples two more times and answer questions three more times if they are randomly chosen to receive lefamulin alone or four more times if they are randomly chosen to receive doxycycline followed by lefamulin during the study. The study team will culture M. genitalium then determine minimum inhibitory concentrations (MICs) to three antibiotics (azithromycin, moxifloxacin, and lefamulin) to see whether it is resistant to any of these antibiotics. The study team will also test for M. genitalium to confirm whether the participants have an infection at baseline and see if lefamulin cured the infection upon completion of the lefamulin.
After 20 patients have been enrolled, the study team will conduct an interim analysis to assess futility. Futility will be defined as less than five percent probability that true efficacy is greater than or equal to 60 percent (i.e., less than or equal to three of the first 10 participants experience microbiologic cure). If neither lefamulin alone nor doxycycline followed by lefamulin meets criteria for futility, the study team will continue the study. If one regimen meets criteria for futility, the study team will drop the regimen that met the criteria for futility and continue to administer the other regimen to the remaining 20 participants. If both regimens meet criteria for futility, the study team will halt the study.
Study participants will be informed of their M. genitalium test of cure results. If the lefamulin does not cure the infection, the study physician will consult with the referring physician who will continue to treat the infection per clinic standard of care.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mycoplasma Genitalium Infection
Keywords
Lefamulin, Doxycycline, M. genitalium
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Lefamulin alone
Arm Type
Experimental
Arm Description
Lefamulin 600mg tablet orally twice daily for 7 days
Arm Title
Doxycycline followed by lefamulin
Arm Type
Experimental
Arm Description
Doxycycline 100mg tablet orally twice daily for 7 days followed by lefamulin 600mg tablet orally twice daily for 7 days
Intervention Type
Drug
Intervention Name(s)
Lefamulin
Other Intervention Name(s)
Xenleta
Intervention Description
600mg tablet orally twice daily
Intervention Type
Drug
Intervention Name(s)
Doxycycline
Intervention Description
100mg tablet orally twice daily
Primary Outcome Measure Information:
Title
Microbiologic cure
Description
Defined as a negative Aptima Mycoplasma genitalium test 21-28 days after completion of the lefamulin
Time Frame
21-28 days after completion of the lefamulin
Secondary Outcome Measure Information:
Title
Microbiologic cure after lefamulin alone compared to microbiologic cure after doxycycline followed by lefamulin
Description
Defined as a negative Aptima Mycoplasma genitalium test 21-28 days after completion of the lefamulin
Time Frame
21-28 days after completion of the lefamulin
Title
Clinical cure
Description
Defined as the absence of symptoms, visible discharge, and other clinical signs (e.g., less than 5 PMNs/HPF on Gram stained smear where available) 21-28 days after completion of the lefamulin
Time Frame
21-28 days after completion of the lefamulin
Title
Reported adherence to lefamulin
Description
Defined by self-reported number of tablets taken
Time Frame
7 days from initial study start if randomized to lefamulin alone; 14 days from initial study start if randomized to lefamulin and doxycycline
Title
Reported adverse events
Description
Defined by self-reported adverse events
Time Frame
42 days from initial study start if randomized to lefamulin alone; 49 days from initial study start if randomized to lefamulin and doxycycline
Title
Sustained microbiologic cure
Description
Defined as a negative Aptima Mycoplasma genitalium test 42-47 days after completion of the lefamulin
Time Frame
42-47 days after completion of the lefamulin
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Physician referral
Persistent symptomatic urogenital M. genitalium infection documented by any nucleic acid amplification test (NAAT) 14-90 days after completion of the prior antimicrobial regimen for M. genitalium
Low risk of reinfection, defined as no unprotected sex with an untreated sex partner since completion of the prior antimicrobial regimen for M. genitalium
Living in the United States
Male or female sex at birth
At least 18 years of age
English-speaking
Able to provide written informed consent
Able to undergo a test to confirm M. genitalium infection at baseline and tests of cure 21-28 days and 42-47 days after completion of the lefamulin
Referring physician willing and able to provide needed patient information
Exclusion Criteria:
Rectal M. genitalium infection only
Females with pelvic inflammatory disease (PID), pregnancy, or currently breastfeeding
Females of reproductive age not on a highly effective method of contraception (i.e., intrauterine device (IUD), Nexplanon, progesterone only depot injection with last injection less than three months prior, oral contraceptive pill and last menstrual period less than 28 days prior)
Known QT prolongation or ventricular arrhythmias including torsades de pointes
Receiving concurrent drugs known to prolong QT interval (i.e., Class IA or III antiarrhythmics, antipsychotics, erythromycin, pimozide, moxifloxacin, tricyclic antidepressants)
Receiving strong or moderate CYP3A or P-gp inducers, strong CYP3A or P-gp inhibitors, moderate CYP3A or P-gp inhibitors, or sensitive CYP3A4 substrates that prolong QT interval
Moderate or severe liver impairment
Known liver disease
Renal failure requiring dialysis
Known allergy to doxycycline, other tetracyclines, and/or lefamulin
Unwilling or unable to undergo a test to confirm M. genitalium infection at baseline or tests of cure 21-28 days and 42-47 days after completion of the lefamulin
Not fluent in English and/or not able to provide written informed consent
Referring physician unwilling or unable to provide needed patient information
At the study physician's discretion
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lisa E Manhart, PhD, MPH
Organizational Affiliation
University of Washington
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lindley Barbee, MD, MPH
Organizational Affiliation
University of Washington
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Not federally funded. Currently no IPD sharing plan.
Learn more about this trial
Lefamulin for M. Genitalium Treatment Failures
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