A phase II/III multi-centre, open-label, parallel group study to prove the non-inferiority of safety and efficacy of Metronidazole/Neomycin Sulfate/ Nystatin, 500mg/ 65.000UI/100.000UI pessaries (Antibiotice SA) versus Tergynan® vaginal tablets (Bouchara–Recordati Laboratories) in the treatment of specific and non-specific vaginitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Antibiotice S.A.

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13], Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

19 Nov 2024 → ongoing

Decision date (initial)

2024-11-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Antibiotice SA

External identifiers

EU CT number

2024-518862-28-00

EudraCT number

2019-002851-40

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Efficacy comparison between Metronidazole/Neomycin Sulfate/ Nystatin, 500mg/ 65.000UI/100.000UI pessaries (Antibiotice SA) and Tergynan® vaginal tablets (Bouchara–Recordati Laboratories) considering the therapeutic cure (both clinical and microbiologic/mycological cure) after a 10-day treatment.

Secondary objectives 2

1. 1. Safety and tolerability profile comparison between Metronidazole/Neomycin Sulfate/ Nystatin, 500mg/ 65.000UI/100.000UI pessaries (Antibiotice SA) and Tergynan® vaginal tablets (Bouchara–Recordati Laboratories)
2. 2. Impact of bacterial vaginosis (BV), respectively vulvovaginal candidiasis (VVC) on Quality of Life (QoL)

Conditions and MedDRA coding

female patients with bacterial vaginosis (BV), respectively vulvovaginal candidiasis (VVC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. 1. Diagnosis of bacterial vaginosis (BV) based on the presence of at least three of the following Amsel criteria: a. Homogeneous vaginal discharge (off white, yellowish, milky or grey, thin), b. positive KOH (whiff test), c. vaginal secretions pH of > 4.5, d. clue cells > /= 20 percent of vaginal squamous epithelial cells on saline "wet mount" or Gram coloration The BV diagnosis will be confirmed by a Nugent score equal or higher than seven on bacteriological analysis of vaginal samples.
2. 2. Diagnosis of vulvovaginal candidiasis (VVC) based on the presence of hyphae or pseudohyphae on KOH or saline preparation; with a vaginal pH less than or equal to 4.5 and clinically must have at least two or more of the following signs and symptoms of VVC, each rated based on severity* with minimum composite score of 2. Signs include vulvovaginal edema, erythema, and/or excoriation. Symptoms include vulvovaginal itching, burning, and/or irritation. *Severity will be graded on a scale of 0-3 (absent = 0; mild = 1; moderate = 2; severe = 3).
3. 3. Post-menarche women, between 18 and 50 years old;
4. 4. Participant is in general good health based on medical history, physical examination, vital signs, and pelvic examination.
5. 5. Subjects who have regular menstrual cycles (Subjects with regular menstrual cycles with intervals between 21 to 35 days)
6. 6. Subject is willing and able to provide written informed consent prior to any study related procedures being performed.
7. 7. Women of child bearing potential must have a negative high sensitivity urine pregnancy test or negative serum pregnancy test result upon entry into the study.
8. 8. Women of childbearing potential must agree to practice reliable contraception* for the 28-day period before enrollment through 30 days following treatment. * Acceptable birth control methods for the purposes of this study may include, but are not limited to, abstinence from intercourse with a malepartner, monogamous relationship with vasectomized partner, barrier methods to include non-lubricated condoms and diaphragms, intrauterine devices, and licensed hormonal methods. NuvaRing® contraceptive use will be prohibited from this study since the device can alter vaginal secretions.
9. 9. Any Pap test performed in the prior 3 years must be normal or ASCUS Human papillomavirus (HPV) negative.
10. 10. Subjects must agree to abstain from sexual intercourse throughout the first 10 days of the study. Following the first 10 days, subjects must agree to use a non-lubricated condom when engaging in sexual intercourse.
11. 11. Subjects must be willing to abstain from alcohol ingestion during the 10 days treatment period and for 1 day afterward.
12. 12. Subjects must agree to refrain from the use of intra-vaginal products throughout the study (e.g., douches, feminine deodorant sprays, spermicides, lubricated condoms, tampons, and diaphragms).
13. 13. Subject is willing and able to cooperate to the extent and degree required by this protocol at the discretion of the investigator.

Exclusion criteria 16

1. 1. Subjects with clinical manifestation of other active vaginal infections, such as infection by Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, Herpes simplex type 2 (HSV-2, or genital herpes) or known infection with HPV, or another vaginal or vulvar condition, that in opinion of the Investigator might confuse interpretation of response to study product. (e.g.- erosive lichen planus, desquamative interstitial vaginitis, contact dermatitis involving the vulvar epithelium, allergy. The above-mentioned infections are detected during clinical examination, as per Investigator’s opinion and experience
2. 2. Subjects diagnosed with cervical intraepithelial neoplasia) class 2 or class 3 (CIN 2 or 3) or carcinoma of the cervix;
3. 3. Subjects who have undergone gynaecological procedures in the month prior to inclusion (such as cauterization of the cervix, cervical biopsy, high-frequency surgery);
4. 4. Subjects who received intravaginal or systemic antimicrobial or antifungal therapy one-month prior randomization;
5. 5. Subjects on immunosuppressive medications (such as corticosteroids, cyclosporine, etc.);
6. 6. Knowledge of positive test result for human immunodeficiency virus or viral hepatitis B or C;
7. 7. Active disease or history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinoma of the skin which is considered cured with minimal risk of recurrence
8. 8. Diabetes Mellitus Type I or Type II;
9. 9. Subjects diagnosed with Pelvic Inflammatory Disease;
10. 10. Participation in any experimental study or ingestion of any experimental drug 12 months before the start of this study;
11. 11. Consumes excessive amounts of alcohol, abuses drugs, or has any condition that would compromise compliance;
12. 12. Subjects who in Investigator's opinion would be non-compliant or Subjects with other vaginal or vulvar conditions, which in the investigator's opinion may confound interpretation of clinical response;
13. 13. Female subjects that are pregnant or lactating or planning to become pregnant during the study period;
14. 14. Virgin female subjects.
15. 15. Subjects who have a known hypersensitivity to components of the formula.
16. 16. Menstruating at the time of diagnosis or expected to menstruated during the course of the treatment (10 days)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants with clinical cure at V2 assessed on BV, respectively VVC group (on each treatment arm). Clinical cure is defined as: a. a score of zero (0) for any sign and symptom scored as 1–2 at baseline; or a score of 0–1 for any sign and symptom scored as 3 at baseline and without the need for further treatment at the discretion of the research clinician) among participants with VVC at baseline, b. absence of all of the following 3 Amsel criteria: Thin, off white, yellowish, mil

Secondary endpoints 11

1. Proportion of participants with microbiological/mycological cure at V2 assessed on BV, respectively VVC group (on each treatment arm) a. Microbiologic cure of BV is defined as a Nugent score of 0-3 b. Mycological cure of VVC is defined as negative Candida culture.
2. Therapeutic cure defined as combination between clinical cure and microbiologic/mycological cure for VVC, respectively BV at V2 (on each treatment arm)
3. Proportion of participants reporting urogenital AEs following the first dose of the study product through V2 among participants with BV ( on each treatment arm).
4. Proportion of participants reporting urogenital AEs following the first dose of the study product through V2 among participants with VVC (on each treatment arm).
5. Proportion of participants reporting serious adverse events (SAEs) considered product-related following the first dose of the study product through V3 among participants with BV (on each treatment arm).
6. Proportion of participants reporting serious adverse events (SAEs) considered product-related following the first dose of the study product through V3 among participants with VVC (on each treatment arm).
7. The proportion of participants experiencing symptom relief (at least one day free of all symptoms) as assessed by the participant. [ Time Frame: Day 1-10]
8. The proportion of participants who need additional treatment per physician opinion following initiation of study treatment and through the final study visit. [Time Frame: Day 1-10]
9. The median time (time defined as earliest time point of reported symptom resolution) to symptom relief (at least one day free of all symptoms) as assessed by the participant. [Time Frame: Day 1-10]
10. Proportion of participants who need additional treatment per physician opinion following initiation of study treatment and through the final study visit.
11. Sustainability of therapeutic cure on each treatment arm from V2 to V3

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Antibiotice S.A.

Sponsor organisation

Antibiotice S.A.

Address

Str Valea Lupului Nr 1

City

Iasi

Postcode

707410

Country

Romania

Scientific contact point

Organisation

Antibiotice S.A.

Contact name

Clinical Trials Center

Public contact point

Organisation

Antibiotice S.A.

Contact name

Clinical Trials Center

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications