Safety, Tolerability, and Acceptability Study of Intravaginal Administration of LABTHERA-001 Capsules in Healthy Women

NCT ID: NCT05587283

Last Updated: 2023-03-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-02

Study Completion Date

2023-05-31

Brief Summary

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This is a phase 1, Single-Center, Double-Blind, Randomized, Placebo-Controlled, dose escalation, clinical trial enrolling 24 healthy participants. The main subject is to investigate the safety and tolerability of the LABTHERA-001 capsule and to explore the acceptability of the capsule.

Detailed Description

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Bacterial vaginosis (BV) is the most common vaginal syndrome frequently found in women. BV is currently mainly treated with antibiotics. However, antibiotic administration can cause various side effects. And one of them is destroying the normal bacteria in the vagina, affecting the balance of the vaginal flora, increasing the likelihood of bacterial vaginosis recurrence, and causing drug resistance of bacteria. Therefore, the importance of fundamental treatment with the recovery of balance in normal vaginal flora is being recognized increasingly. The study drug for this trial, LABTHERA-001, has been derived from the bacteria Lactobacillus plantarum ATG-K2. Administration of the ATG-K2 strain will temporarily colonize the vagina to encourage a more normal microbiome.

The main goals of this study are 1. to determine whether LABTHERA-001 is safe and well tolerated in healthy adult women. And 2. to investigate the acceptability of the LABTHERA-001 capsule or matching placebo by completing a satisfaction evaluation questionnaire.

Conditions

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Bacterial Vaginosis Vaginal Disease Bacterial Infections Vaginitis Infection, Bacterial

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Eight participants will be randomized to be allocated into either a treatment group or a placebo control group (3:1 ratio) for each cohort. There will be three ascending dose cohorts. For the first two doses, the next dose cohorts will begin enrollment only after the safety data review meets a satisfactory evaluation by the safety review committee.
Primary Study Purpose

OTHER

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Low dose LABTHERA-001 capsule

Low dose LABTHERA-001 capsule (0.2 x 10\^9 CFU), administered intravaginally once a day for 7 consecutive days.

Group Type EXPERIMENTAL

Experimental: Low dose LABTHERA-001 capsule

Intervention Type DRUG

Low dose LABTHERA-001 capsule, 0.2 x 10\^9 CFU/capsule with excipients.

Medium dose LABTHERA-001 capsule

Medium dose LABTHERA-001 capsule (1 x 10\^9 CFU), administered intravaginally once a day for 7 consecutive days.

Group Type EXPERIMENTAL

Experimental: Medium dose LABTHERA-001 capsule

Intervention Type DRUG

Medium dose LABTHERA-001 capsule, 1 x 10\^9 CFU/capsule with excipients.

High dose LABTHERA-001 capsule

High dose LABTHERA-001 capsule (5 x 10\^9 CFU), administered intravaginally once a day for 7 consecutive days.

Group Type EXPERIMENTAL

Experimental: High dose LABTHERA-001 capsule

Intervention Type DRUG

High dose LABTHERA-001 capsule, 5 x 10\^9 CFU/capsule with excipients.

Low dose Placebo capsule

Low dose Placebo (excipients of the study drug) capsule administered intravaginally once a day for 7 consecutive days.

Group Type PLACEBO_COMPARATOR

Placebo Comparator: Low dose Placebo capsule

Intervention Type OTHER

Medium dose Placebo capsule, filled with excipients; Lactose, and magnesium stearate.

Medium dose Placebo capsule

Medium dose Placebo capsule (excipients of the study drug) administered intravaginally once a day for 7 consecutive days.

Group Type PLACEBO_COMPARATOR

Placebo Comparator: Medium dose Placebo capsule

Intervention Type OTHER

Medium dose Placebo capsule, filled with excipients; Lactose, and magnesium stearate.

High dose Placebo capsule

High dose Placebo capsule (excipients of the study drug) administered intravaginally once a day for 7 consecutive days.

Group Type PLACEBO_COMPARATOR

Placebo Comparator: High dose Placebo capsule

Intervention Type OTHER

High dose Placebo capsule, filled with excipients; Lactose, and magnesium stearate.

Interventions

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Experimental: Low dose LABTHERA-001 capsule

Low dose LABTHERA-001 capsule, 0.2 x 10\^9 CFU/capsule with excipients.

Intervention Type DRUG

Experimental: Medium dose LABTHERA-001 capsule

Medium dose LABTHERA-001 capsule, 1 x 10\^9 CFU/capsule with excipients.

Intervention Type DRUG

Experimental: High dose LABTHERA-001 capsule

High dose LABTHERA-001 capsule, 5 x 10\^9 CFU/capsule with excipients.

Intervention Type DRUG

Placebo Comparator: Low dose Placebo capsule

Medium dose Placebo capsule, filled with excipients; Lactose, and magnesium stearate.

Intervention Type OTHER

Placebo Comparator: Medium dose Placebo capsule

Medium dose Placebo capsule, filled with excipients; Lactose, and magnesium stearate.

Intervention Type OTHER

Placebo Comparator: High dose Placebo capsule

High dose Placebo capsule, filled with excipients; Lactose, and magnesium stearate.

Intervention Type OTHER

Other Intervention Names

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Lactobacillus Plantarum ATG-K2 Lactobacillus Plantarum ATG-K2 Lactobacillus Plantarum ATG-K2 Control substance Control substance Control substance

Eligibility Criteria

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Inclusion Criteria

1. Healthy non-smoking woman aged 18 to 45 years old as of the date of written consent
2. Agrees to maintain her contraceptive method during the clinical trial if she has regular menstrual cycles (21-35 days) or has had amenorrhea for more than 12 weeks before the Screening Visit due to continued use of long-acting progestin or oral contraceptives.
3. Confirmed normal cervical screen test (CST) performed at the Screening Visit
4. Has had sexual experiences that included vaginal intercourse
5. Has experienced gynecological examinations previously
6. Agrees to discontinue the use of the following during the clinical trial period (Screening Visit to End of study visit or early termination visit):

* products for vaginal insertion (e.g., tampons, menstrual cups, etc.)
* Other vaginal products (e.g., contraceptive creams, vaginal cleaners, lubricants, etc.)
7. Agrees to be sexually abstinent from 72 hours before the Day 1 visit until the first study visit after final administration of IP (nominally the Day 9 visit).
8. Agrees to continue to use the following highly effective contraceptive methods during the clinical trial period and for at least 30 days after the final dose of study treatment, if woman of child-bearing potential (has experienced menarche and is not permanently sterile or postmenopausal):

* Female: combined (estrogen and progestogen containing) hormonal/ contraception associated with inhibition of ovulation (oral or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD; if inserted more than 12 weeks before the Screening visit), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner, sexual abstinence
* Male partner: 'Vasectomy,' 'condom'
9. Able and willing to insert a hard capsule into her vagina
10. Able and willing to answer questions about her health status and sexual life
11. Able and willing to undergo vaginal and cervical examinations by the Investigator
12. Agrees and can comply with the planned clinical trial procedures after receiving a full explanation and voluntarily decides to participate and gives written informed consent

Exclusion Criteria

1. Confirmed to have the following urogenital infections from the vaginal discharge test performed at the Screening Visit, or had the following diagnosed urogenital infections within three weeks before the Screening Visit, or has a history of clinically significant urogenital infections at the discretion of the Investigator:

• Urinary tract infection, bacterial vaginosis, candida vaginitis, trichomonas vaginalis, Neisseria gonorrhoeae, chlamydia trachomatis, treponema pallidum, herpes simplex
2. History of recurrent genital herpes
3. Has the following diagnosed urogenital infections, or had two or more clinically significant urogenital infections within 24 weeks before the Screening Visit, at the discretion of the Investigator:

• \[Gonococcus, chlamydia trachomatis, syphilis treponema, trichomonas vaginitis, candida vaginitis, etc.\]
4. Has vaginitis symptoms (abnormal vaginal discharge, itching, burning sensation, etc.) at Screening or pre-dose at the Day 1 visit, or between the Screening and Day 1 visits.
5. Is pregnant, lactating, within eight weeks of childbirth, or is planning pregnancy within 60 days of the last dose of IP.
6. Is menopausal, defined as being amenorrhoeic for at least 12 months without an alternative cause.
7. Has had an intrauterine device (IUD) inserted within 12 weeks before the Screening Visit
8. Underwent pelvic surgery within 12 weeks before the Screening Visit
9. Received cervical cryotherapy or cervical laser treatment within 12 weeks before the Screening Visit
10. Started to use long-acting hormonal contraceptives within 12 weeks before the Screening Visit \[e.g., DMPA (depot formulation including medroxyprogesterone acetate)\] (However, participants who have continuously used the contraceptive for more than 12 weeks can be enrolled at the discretion of the Investigator.)
11. Has a clinically significant medical history or current medical condition as assessed by the Investigator including but not limited to the cardiovascular system, respiratory system, kidney, endocrine system, hematology, digestive system, central nervous system, psychiatric disorder, or infectious disease, that may affect the safety evaluation of the investigational product or jeopardize the individual's involvement in the study. History of any cancer (including non-melanoma skin cancer) is exclusionary.
12. Positive test for SARS-CoV-2 (COVID-19) during the Screening period and pre-dose at the Day 1 visit (may be re-screened when eligible).
13. Positive diagnosis of human immunodeficiency virus (HIV), hepatitis B or C at the Screening Visit
14. Confirmed to have severe damage to the vaginal epithelium in the physical examination at the Screening Visit
15. Used immunosuppressants within four weeks before the Screening Visit
16. Used antibiotics or antifungals within three days before the Screening Visit (However, enrollment is possible if the individual agrees to a washout period equivalent to three times or more the half-life of the corresponding drugs as of the randomization date.)
17. History of hypersensitivity reactions to the components of the study drug or history of other serious drug hypersensitivity reactions, at the discretion of the Investigator
18. History of or current drug or alcohol abuse; or tests positive to urine drug screen or alcohol breath test at the Screening or Day 1 visits; or does not agree to abstain from alcohol 24 hours before each study visit and to consume no more than 10 standard drinks per week with no more than 4 standard drinks on any one day at any other time during their participation in the study. One standard drink contains 10 g alcohol. Urine drug screen may be repeated once only at the discretion of the Investigator.
19. Current tobacco smoker; or smoked more than one pack of cigarettes (or tobacco equivalent) per day for more than 10 years; or uses nicotine-replacement therapy (including vaping); or does not agree to abstain from using tobacco or nicotine-containing products during the study.
20. Received other investigational products within four weeks before the Screening Visit
21. Received COVID-19 vaccination or any other vaccination within 8 weeks before the first dose of IP, and/or is planning or scheduled to be vaccinated (including COVID-19 initial, second or booster dose) during the study period up to the final follow-up visit.
22. Judged by the Investigator to be unsuitable for participation in this clinical trial.
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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ATOGEN AUSTRALIA PTY LTD

UNKNOWN

Sponsor Role collaborator

AtoGen Co. Ltd

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christopher Argent, Dr.

Role: PRINCIPAL_INVESTIGATOR

Scientia Clinical Research Ltd

Locations

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Scientia Clinical Research

Randwick, New South Wales, Australia

Site Status RECRUITING

Countries

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Australia

Central Contacts

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Scientia Clinical Research Study Team

Role: CONTACT

+61 02 9382 5800

AtoGen Assistant Manager

Role: CONTACT

+82 70 7725 2203

Facility Contacts

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Christopher Argent, Dr.

Role: primary

+61 02 9382 5800

References

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Mastromarino P, Vitali B, Mosca L. Bacterial vaginosis: a review on clinical trials with probiotics. New Microbiol. 2013 Jul;36(3):229-38. Epub 2013 Jun 30.

Reference Type BACKGROUND
PMID: 23912864 (View on PubMed)

Kenyon C, Colebunders R, Crucitti T. The global epidemiology of bacterial vaginosis: a systematic review. Am J Obstet Gynecol. 2013 Dec;209(6):505-23. doi: 10.1016/j.ajog.2013.05.006. Epub 2013 May 6.

Reference Type BACKGROUND
PMID: 23659989 (View on PubMed)

Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I, Reno H, Zenilman JM, Bolan GA. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021 Jul 23;70(4):1-187. doi: 10.15585/mmwr.rr7004a1.

Reference Type BACKGROUND
PMID: 34292926 (View on PubMed)

Vicariotto F, Mogna L, Del Piano M. Effectiveness of the two microorganisms Lactobacillus fermentum LF15 and Lactobacillus plantarum LP01, formulated in slow-release vaginal tablets, in women affected by bacterial vaginosis: a pilot study. J Clin Gastroenterol. 2014 Nov-Dec;48 Suppl 1:S106-12. doi: 10.1097/MCG.0000000000000226.

Reference Type BACKGROUND
PMID: 25291116 (View on PubMed)

De Seta F, Parazzini F, De Leo R, Banco R, Maso GP, De Santo D, Sartore A, Stabile G, Inglese S, Tonon M, Restaino S. Lactobacillus plantarum P17630 for preventing Candida vaginitis recurrence: a retrospective comparative study. Eur J Obstet Gynecol Reprod Biol. 2014 Nov;182:136-9. doi: 10.1016/j.ejogrb.2014.09.018. Epub 2014 Sep 17.

Reference Type BACKGROUND
PMID: 25305660 (View on PubMed)

Strus M, Chmielarczyk A, Kochan P, Adamski P, Chelmicki Z, Chelmicki A, Palucha A, Heczko PB. Studies on the effects of probiotic Lactobacillus mixture given orally on vaginal and rectal colonization and on parameters of vaginal health in women with intermediate vaginal flora. Eur J Obstet Gynecol Reprod Biol. 2012 Aug;163(2):210-5. doi: 10.1016/j.ejogrb.2012.05.001. Epub 2012 Jun 19.

Reference Type BACKGROUND
PMID: 22721635 (View on PubMed)

Hemalatha R, Mastromarino P, Ramalaxmi BA, Balakrishna NV, Sesikeran B. Effectiveness of vaginal tablets containing lactobacilli versus pH tablets on vaginal health and inflammatory cytokines: a randomized, double-blind study. Eur J Clin Microbiol Infect Dis. 2012 Nov;31(11):3097-105. doi: 10.1007/s10096-012-1671-1. Epub 2012 Jul 10.

Reference Type BACKGROUND
PMID: 22777592 (View on PubMed)

Other Identifiers

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LT-001

Identifier Type: -

Identifier Source: org_study_id

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