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Trial registered on ANZCTR


Registration number
ACTRN12619000295145
Ethics application status
Approved
Date submitted
20/02/2019
Date registered
26/02/2019
Date last updated
10/11/2022
Date data sharing statement initially provided
26/02/2019
Date results information initially provided
10/11/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Pharmacokinetics of Intravaginal Lactoferrin Preparations
Scientific title
Evaluation of the Effects of Various Intravaginal MTbLF (bovine lactoferrin) Formulations on bLF Metabolism in Vaginal Fluid in pre-menopausal females with symptomatic bacterial vaginosis
Secondary ID [1] 297447 0
Protocol MT300V-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bacterial Vaginosis 309466 0
Condition category
Condition code
Infection 308308 308308 0 0
Studies of infection and infectious agents
Renal and Urogenital 310300 310300 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Metrodora Therapeutics bovine Lactoferrin [MTbLF] will be administered intravaginally (into the vagina) using a single use applicator. The formulation contains 300 mg of MTbLF (bovine lactoferrin) along with filler, thickener, mucoadhesive gelling agent, glidant and lubricant (excipients). The excipients are all compendial inactive ingredients commonly used in vaginally administered products. Patients will receive 10 daily doses of study medication. Patients will receive 3 doses of a single formulation in the clinical unit administered by a healthcare practitioner separated by 24 hours in consecutive days of their preference. The remaining days, they will self-administer the same formulation daily at home. Adherence to dosing will be monitored by clinical personnel over the course of the 3 nights/2 days in-clinic treatment period and by monitoring a patient home dosing record along with counting tablets during the at home dosing period.
Intervention code [1] 312282 0
Treatment: Drugs
Comparator / control treatment
Uncontrolled
Control group
Uncontrolled

Outcomes
Primary outcome [1] 307272 0
Assessment of 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) and/or SDS-PAGE to determine concentrations of MTbLF.
Timepoint [1] 307272 0
At the baseline visit, prior to the first dosing. At 0 hours post 1st in-clinic dose and at 24 hours post 1st and 2nd in-clinic dose. At 2 hours, 4 hours, 8 hours, 12 hours and 18 hours post dose for the in-clinic stay. At 12±2 hours post dose for the 3rd in-clinic dose and the 7 daily home doses.
Primary outcome [2] 307281 0
Assessment of safety through medical review of adverse events and serious adverse events, physical and abbreviated gynecological examinations, vital signs and clinical laboratory tests. This is the first in human study with vaginally administered MTbLF. However, other vaginal administered bovine lactoferrin (bLF) preparations have been studied in humans and have been found to be well-tolerated. While there are no known identified or potential risks with the use of MTbLF intravaginally, patients will be closely monitored for safety and tolerability.
Timepoint [2] 307281 0
Adverse events will be assessed from the time the patient provides informed consent through the end of the Follow Up Visit, which will occur once between Day 21 to Day 35 after receiving the first dose. Serious adverse events will be assessed from the time the patient provides informed consent until 30 days after the last dose. Physical and abbreviated gynecological examination will take place at screening visit and at final visit, 11 days post initial dose. Vital signs will take place at screening visit, at baseline visit prior to initial dose, at Day 6 and at the final visit, 11 days post initial dose. Clinical laboratory tests will take place at screening visit, 6 days post initial dose and at the final visit, 11 days post initial dose.
Secondary outcome [1] 351322 0
Assessment of the vaginal microbiota. Assessment by 16S rRNA, using RT-PCR.
Vaginal swabs will be collected and analyzed by RT-PCR and 16S rRNA gene sequencing to identify bacterial species present.
Timepoint [1] 351322 0
At the baseline visit, prior to first dosing, at T=12 hours during in-clinic visits and at 12 ± 2 hours post each daily home dose and at final visit (Day 11). At the Follow Up Visit 21 to 35 days after first dose of study medication.
Secondary outcome [2] 367107 0
Assess changes in MTbLF iron saturation and the residual ability of MTbLF to chelate available iron in vaginal fluid samples after administration of various formulations.

This is a composite secondary outcome. Vaginal fluid will be isolated from vaginal swabs and analyzed spectrophotometrically.
Timepoint [2] 367107 0
At the baseline visit, prior to the first dosing. At 0 hours post 1st in-clinic dose and at 24 hours post 1st and 2nd in-clinic dose. At 2 hours, 4 hours, 8 hours, 12 hours and 18 hours post dose for the in-clinic stay. At 12±2 hours post dose for the 3rd in-clinic dose and the 7 daily home doses.
Secondary outcome [3] 367255 0
This is a primary outcome-Assessment of 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 [3] 367255 0
At the baseline visit, prior to the first dosing. At 0 hours post 1st in-clinic dose and at 24 hours post 1st and 2nd in-clinic dose. At 2 hours, 8 hours and 12 hours post 1st and 2nd in-clinic dose and at final visit, 11 days post initial dose.
Secondary outcome [4] 367258 0
Assessment of the bacterial vaginosis (BV) status. Three vaginal swabs will be collected to assess BV status. The first swab will be used for Amsel criteria. The second swab will be used for Gram Stain/Nugent Score. The third vaginal swab will be used for a PCR-based assessment of BV (AusDiagnostics Vaginosis and Vaginitis PCR test).
Timepoint [4] 367258 0
PCR-based assessment of BV (AusDiagnostics Vaginosis and Vaginitis PCR test) at screening to confirm eligibility. Also, at baseline visit prior to first dosing, at T=12 hours during in-clinic visits and 12 ±2 hours post each daily home dose, at final visit (Day 11) and at the Follow Up Visit that will be done once between Day 21 and Day 35 after receiving the first dose. For Amsel criteria, at baseline visit, Day 8, at final visit (Day 11) and at the Follow Up Visit that will be done once between Day 21 and Day 35 after receiving the first dose. For Gram stain/Nugent Score, at baseline visit, Day 8, at final visit (Day 11) and at the Follow Up Visit that will be done once between Day 21 and Day 35 after receiving the first dose.

Eligibility
Key inclusion criteria
1. In Part 1 and Part 2, premenopausal healthy females or pre-menopausal females with asymptomatic BV age 18 - 50 years old. In Part 3, pre-menopausal females with symptomatic BV age 18 - 45 years old who test positive for BV (AusDiagnostics Vaginitis and Vaginosis PCR test of “Flora consistent with Bacterial Vaginosis”)
2. Able to understand and sign informed consent form prior to initiation of any study-related procedures
3. Able to commit to in-clinic monitoring over a 3-night period for scheduled visits and assessments
4. Able to return to the clinic daily for scheduled assessments for the 7 days of home dosing and for a Follow Up Visit 21 to 35 days after first dose of study medication
5. Willing to abstain from sexual activity 24 hours before dosing and Day -1 through Day 11
6. Body Mass Index (BMI) range of 18-35.0
Minimum age
18 Years
Maximum age
45 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Currently pregnant or lactating
2. Menopausal
3. Anticipate menstruation to occur during the in-clinic period of the study
4. Women with with greater than or equal to 4 episodes of treatment for symptomatic vaginal infections during the past year (women with a history of BV are allowed)
5. Currently receiving, or requiring during the study, other intravaginal treatment of any kind (e.g., tablet, suppository, cream, gel, foam, vaginal ring, douching, etc.). Intrauterine devices (e.g., IUD) are acceptable.
6. Gynecologic surgery in past 3 months
7. Received antifungal or antimicrobial therapy (systemic or intravaginal) within the last 14 days prior to study drug administration.
8. HIV positive or has previously tested positive for any STD within the last 30 days
9. Test positive by AusDiagnostics Vaginitis and Vaginosis PCR test at screening for trichomoniasis or candidiasis
10. Diagnosis of cervical intra-epithelial neoplasia or cervical carcinoma
11. Any abnormal anatomy or pathology of the vagina
12. Taking concomitant diuretics
13. History of allergy to bovine milk, bovine milk products, lactoferrin, or components of the MTbLF Drug Product.
14. 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.
15. Regular smokers unwilling to abstain from smoking for the duration of the 3-day in-clinic part of the study. Subjects who smoke but are willing and able to abstain for the 3-day in-clinic study duration can be included.
16. Asthma requiring preventer medication. Subjects with mild asthma requiring an occasional reliever inhaler can be included.

Study design
Purpose of the study
Treatment
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
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
27/02/2019
Actual
28/02/2019
Date of last participant enrolment
Anticipated
Actual
16/08/2021
Date of last data collection
Anticipated
Actual
8/09/2021
Sample size
Target
24
Accrual to date
Final
18
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 300553 0
Commercial sector/Industry
Name [1] 300553 0
Metrodora Therapeutics Pty Ltd
Country [1] 300553 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Metrodora Therapeutics Pty Ltd
Address
58 Gipps Street, Collingwood, 3066 VIC
Country
Australia
Secondary sponsor category [1] 300037 0
None
Name [1] 300037 0
Address [1] 300037 0
Country [1] 300037 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301347 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 301347 0
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 301347 0
Australia
Date submitted for ethics approval [1] 301347 0
Approval date [1] 301347 0
08/10/2018
Ethics approval number [1] 301347 0

Summary
Brief summary
This research study in BV patients is testing the safety, tolerability, pharmacokinetics (the levels of drug in the blood and in vaginal fluid) of a formulation of a drug called Metrodora Therapeutics bovine Lactoferrin (MTbLF) when it is given Intravaginally (into the vagina). 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 Bacterial Vaginosis (BV). The overall goal of this study is to optimize the formulation to test in future studies as a treatment for BV.
BV patients will receive 10 daily doses of study medication; 3 doses of a single formulation in the clinical unit separated by 24 hours in consecutive days of their preference and the remaining days, they will self-administer the same formulation daily. A series of vaginal swabs and blood samples will be collected over a 24-hour period following each of the two first doses in clinic, once approximately 12 hours after the third in-clinic dose and after each home dosing and at the Follow Up visit 21 to 35 days after first dose of study medication .
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 86690 0
Dr Aarthy Joseph
Address 86690 0
Nucleus Network Pty Ltd
Level 5
89 Commercial Road
Melbourne, VIC 3004
Country 86690 0
Australia
Phone 86690 0
+61 385939894
Fax 86690 0
Email 86690 0
[email protected]
Contact person for public queries
Name 86691 0
Dr Aarthy Joseph
Address 86691 0
Nucleus Network Pty Ltd
Level 5
89 Commercial Road
Melbourne, VIC 3004
Country 86691 0
Australia
Phone 86691 0
+61 385939894
Fax 86691 0
Email 86691 0
[email protected]
Contact person for scientific queries
Name 86692 0
Dr Gary Gelbfish
Address 86692 0
Metrodora Therapeutics
2502 Avenue I,
Brooklyn, NY 11210
USA
Country 86692 0
United States of America
Phone 86692 0
+1-9176136162
Fax 86692 0
Email 86692 0
[email protected]

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
SourceTitleYear of PublicationDOI
EmbaseCharacterization of proteolytic degradation products of vaginally administered bovine lactoferrin.2022https://dx.doi.org/10.1371/journal.pone.0268537
EmbaseProteolysis of vaginally administered bovine lactoferrin: clearance, inter-subject variability, and implications for clinical dosing.2023https://dx.doi.org/10.1007/s10534-022-00481-7
N.B. These documents automatically identified may not have been verified by the study sponsor.