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Trial registered on ANZCTR


Registration number
ACTRN12622000548730
Ethics application status
Approved
Date submitted
23/03/2022
Date registered
7/04/2022
Date last updated
7/04/2024
Date data sharing statement initially provided
7/04/2022
Date results information initially provided
15/02/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety and Preliminary Efficacy of Intravaginal Low Iron Lactoferrin following antibiotic treatment on the incidence of recurrent bacterial vaginosis (BV)
Scientific title
Single arm, Phase 1b, repeat dose study to assess the safety and preliminary evidence of efficacy of Metrodora Therapeutics’ bovine lactoferrin (low iron MTbLF) on the recurrence of bacterial vaginosis (BV) in premenopausal females following treatment with vaginal metronidazole
Secondary ID [1] 306744 0
Protocol MT300V-103
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bacterial Vaginosis 325749 0
Condition category
Condition code
Infection 323086 323086 0 0
Studies of infection and infectious agents
Renal and Urogenital 323087 323087 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Metrodora Therapeutics Low Iron bovine Lactoferrin [Low Iron MTbLF] will be administered as a bilayer tablet intravaginally (into the vagina) using a single use applicator. Each tablet contains 300 mg of Low Iron MTbLF (bovine lactoferrin). Patients will self-administer 84 daily doses of study medication. Adherence to dosing will be monitored by clinical personnel through daily patient diary screening and study drug accountability (tablet count) during 4 visits over the course of the 12-week treatment period.
Intervention code [1] 323191 0
Prevention
Intervention code [2] 323303 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 330850 0
Assessment of safety of daily intravaginal administration for 12 weeks through medical review of serious adverse events and adverse events such as local mucosal irritation assessed by patients’ self-report and physical and abbreviated gynecological examinations, vital signs, and clinical laboratory blood tests and urinalysis.
Timepoint [1] 330850 0
Adverse events will be assessed from the time the patient provides informed consent through the end of the study. Physical examination will take place at screening visit, visit 1 (enrollment visit), visit 2 (two weeks post-first dose), visit 3 (four weeks post-first dose), visit 4 (eight weeks post-first dose), visit 5 (twelve weeks post-first dose) and end of study visit (twenty-four weeks post-first dose). Abbreviated gynecological examination will take place at screening visit, visit 1 (enrollment visit), visit 2 (two weeks post-first dose), visit 3 (four weeks post-first dose), visit 4 (eight weeks post-first dose), visit 5 (twelve weeks post-first dose) and end of study visit (twenty-four weeks post-first dose). Vital signs will take place at screening visit, visit 1 (enrollment visit), visit 2 (two weeks post-first dose), visit 3 (four weeks post-first dose), visit 4 (eight weeks post-first dose), visit 5 (twelve weeks post-first dose) and end of study visit (twenty-four weeks post-first dose). Clinical laboratory tests and urinalysis will take place at screening visit, visit 2 (two weeks post-first dose), visit 3 (four weeks post-first dose), visit 4 (eight weeks post-first dose) and visit 5 (twelve weeks post-first dose).
Secondary outcome [1] 407813 0
Determination of BV recurrence after repeated doses of low iron MTbLF through Amsel criteria assessment and Nugent score (BV defined as the presence of at least 3 out of 4 positive Amsel criteria and a Nugent score 4-10) at or by the end of treatment (12 weeks following treatment of BV with vaginal metronidazole). This is a composite outcome determined by the requirement that both Amsel (clinical diagnosis) and Nugent score (microbial diagnosis) need to be assessed as BV positive for determining BV recurrence.
Timepoint [1] 407813 0
Secondary timepoint (1): Prior to first dosing on visit 1 (enrollment visit), visit 2 (two weeks post-first dose), visit 3 (four weeks post-first dose), visit 4 (eight weeks post-first dose) and visit 5 (twelve weeks post-first dose).
Secondary outcome [2] 407814 0
Determination of BV recurrence after repeated doses of low iron MTbLF through Amsel criteria assessment and Nugent score (BV defined as the presence of at least 3 out of 4 positive Amsel criteria and a Nugent score 4-10) at or by 24 weeks (24 weeks after 1st dose administration, 12 weeks after end of treatment).
Timepoint [2] 407814 0
Prior to first dosing on visit 1 (enrollment visit), visit 2 (two weeks post-first dose), visit 3 (four weeks post-first dose), visit 4 (eight weeks post-first dose), visit 5 (twelve weeks post-first dose) and visit 8 (twenty-four weeks post-first dose, at end of study).
Secondary outcome [3] 407815 0
Assessment of Low Iron MTbLF concentrations in vaginal fluid using standard laboratory methods. Vaginal fluid will be isolated from vaginal swabs and analyzed by high performance liquid chromatography (HPLC) to determine concentrations of Low Iron MTbLF.
Timepoint [3] 407815 0
At screening visit, prior to the first dosing at the enrollment visit, at around 12 hours post dose on visits 2, 3, 4 and 5 (weeks 2, 4, 8 and 12 post-first dose respectively) and at the end of the study visit (twenty-four weeks post-first dose).
Secondary outcome [4] 407816 0
Assessment of Low Iron MTbLF concentrations in blood samples using standard laboratory methods. Levels of MTbLF will be quantified in plasma using an enzyme-linked immunosorbent assay (ELISA) specific for bovine lactoferrin.
Timepoint [4] 407816 0
Prior to first dosing on visit 1 (enrollment visit) and at around 12 hours post dose on visits 2, 3, 4 and 5 (weeks 2, 4, 8 and 12 respectively).

Eligibility
Key inclusion criteria
1. Premenopausal females aged 18-45 with a diagnosis of BV confirmed by at least 3 out of 4 positive Amsel criteria (must collect all 4 Amsel criteria):
a. Off-white (milky or gray), thin, homogeneous discharge with minimal or absent pruritus and inflammation of the vulva and vagina
b. Vaginal secretion pH of greater than 4.5
c. A fishy odor (i.e., a positive whiff test) of the vaginal discharge with the addition of a drop of KOH
d. The presence of clue cells greater than 20 percent of the total epithelial cells on microscopic examination of the saline wet mount
2. Nugent score of 4 to 10 prior to antibiotic treatment
3. Willing to complete a course of metronidazole (vaginal for 5 days)
4. Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks, and adverse effects
5. Regular predictable menstrual cycles or amenorrheic for at least 3 months due to use of a long-acting progestin or continuous use of oral contraceptives
6. Must be of non-childbearing potential or if of childbearing potential, must agree to use a reliable method of birth control for 3 months after last dose of study drug treatment. (Reliable methods of birth control include tubal ligation, male partner with a vasectomy, a steroidal contraceptive (oral, patch, injectable or implantable), IUD, condoms or abstinence)
Minimum age
18 Years
Maximum age
45 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Anticipate having 6 or more different sexual partners over the 24 week course of the study
2. Currently pregnant, lactating or within the first 2 months postpartum
3. Planning to donate ova within 3 months of study completion
4. Urogenital infection at screening
Note: Urogenital infection includes urinary tract infection, Trichomonas (T.) vaginalis, Neisseria (N.) gonorrhoeae, Chlamydia (C.) trachomatis, Mycoplasma genitalium, Treponema pallidum or vulvo-vaginal candidiasis
5. Positive for HIV or Hepatitis B or C, or herpes simplex virus active lesions at screening, or has previously tested positive for any STD within the last 30 days
6. Currently receiving, or requiring during the study, other intravaginal treatment of any kind (e.g., tablet, suppository, cream, gel, foam, vaginal ring, etc.)
7. Gynecologic surgery in past 2 months, including IUD insertion or removal, pelvic surgery, cervical cryotherapy or cervical laser treatment
8. Received antifungal or antibacterial therapy other than metronidazole (systemic or intravaginal) within the last 14 days prior to enrolment
9. Use of disulfiram within past 2 weeks or other contraindication to use of vaginal metronidazole
10. Any condition requiring regular periodic use of systemic antibiotics during participation in the study
11. Under treatment for cervical intra-epithelial neoplasia or cervical carcinoma
12. Patients with another vaginal or vulvar condition, which would confound the interpretation of clinical response
13. Taking concomitant diuretics or probiotics or use of vaginal acidifying agents
14. Failure to complete prescribed days of metronidazole with the last dose taken no later than 48 hours prior to allocation to treatment
15. History of allergy to bovine milk, bovine milk products, lactoferrin, or components of the low iron MTbLF Drug Product. Patients with oral lactose intolerance are eligible for the study
16. Received another investigational agent within 4 weeks prior to screening or within 5 half-lives of the investigational agent, whichever is greater, or planned receipt of an investigational agent not specified by this protocol during the study period

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
27/04/2022
Actual
30/08/2022
Date of last participant enrolment
Anticipated
Actual
2/08/2023
Date of last data collection
Anticipated
30/09/2024
Actual
9/02/2024
Sample size
Target
24
Accrual to date
Final
19
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 23555 0
East Sydney Doctors - Darlinghurst
Recruitment postcode(s) [1] 38977 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 311080 0
Commercial sector/Industry
Name [1] 311080 0
Metrodora Therapeutics Pty Ltd
Country [1] 311080 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Metrodora Therapeutics Pty Ltd
Address
Level 7, 330 Collins Street, Melbourne Victoria 3000, Australia
Country
Australia
Secondary sponsor category [1] 312410 0
None
Name [1] 312410 0
Address [1] 312410 0
Country [1] 312410 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310617 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 310617 0
123 Glen Osmond Road, Eastwood SA 5063
Ethics committee country [1] 310617 0
Australia
Date submitted for ethics approval [1] 310617 0
Approval date [1] 310617 0
21/03/2022
Ethics approval number [1] 310617 0

Summary
Brief summary
This research study in BV patients is testing the safety, tolerability, preliminary evidence of efficacy and pharmacokinetics (the levels of drug in the blood and in vaginal fluid) of a bilayer tablet formulation of a drug called Metrodora Therapeutics Low Iron bovine Lactoferrin (Low Iron MTbLF) when it is given Intravaginally (into the vagina) after patients’ completion of primary treatment with antibiotics. Lactoferrin is a naturally occurring protein present in milk, saliva, tears, and other bodily fluids that has antimicrobial activity and may have an important therapeutic effect for the treatment of recurrent Bacterial Vaginosis (BV). The overall goal of this study is to optimize the duration of Low Iron MTbLF treatment post antibiotics for the prevention of recurrence of BV and the evaluation of different diagnostics to follow recurrence during the treatment period.
BV patients will receive antibiotic treatment (metronidazole 0.75% intravaginal daily for 5 days at bedtime) for symptomatic BV. Then, they will self-administer daily doses of study medication for 12 weeks. They will self-collect three vaginal swabs weekly at home for the duration of the 12-week treatment and then the 12-week follow up period. A series of vaginal swabs and blood samples will be collected by a healthcare practitioner during 4 in-clinic visits that will take place in the 12-week treatment period and at the end of the study on week 24. Patients will use a patient diary to record symptoms, dosing of study medication and other study-related information daily during treatment (weeks 1 to 12) and twice a week during weeks 13-24.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 118278 0
Dr Catherine Insley
Address 118278 0
East Sydney Doctors
102 Burton Street, Darlinghurst 2010, New South Wales
Country 118278 0
Australia
Phone 118278 0
+61 29332 2531
Fax 118278 0
Email 118278 0
trials@eastsydneydoctors.com.au
Contact person for public queries
Name 118279 0
Dr Catherine Insley
Address 118279 0
East Sydney Doctors
102 Burton Street, Darlinghurst 2010, New South Wales
Country 118279 0
Australia
Phone 118279 0
+61 29332 2531
Fax 118279 0
Email 118279 0
trials@eastsydneydoctors.com.au
Contact person for scientific queries
Name 118280 0
Dr Gary Gelbfish
Address 118280 0
Metrodora Therapeutics
2502 Avenue I,
Brooklyn, NY 11210
Country 118280 0
United States of America
Phone 118280 0
+19176136162
Fax 118280 0
Email 118280 0
ggelbfish@metrodora.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.