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Distal Subungual OnychomycosisPhase 2NCT04188574

A Trial Involving Treatment of BB2603 in Subjects With Distal Subungual Onychomycosis of the Toenail

A Phase 2 study testing BB2603-1, BB2603-3 and BB2603-10 in people with Distal Subungual Onychomycosis and Fungal Infection, run by Blueberry Therapeutics at 20 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study will be a multicenter, international, randomized, vehicle-controlled, parallel-group, double-blinded study. Subjects who are eligible to participate with a confirmed diagnosis of Distal Subungual onychomycosis (DSO) of the toenail will be randomized and participate in one of the following treatment groups… Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
BB2603-1, BB2603-3 and BB2603-10
Could I receive a placebo?
No, everyone receives an active treatment
How many people
111 participants
Where
20 sitesin 3 countries
Study dates
22 Mar 2021to 28 Jun 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female ≥18 (and ≤99) at the time of Informed Consent.
  • Clinically and mycologically (KOH and culture positive for dermatophytes [microbial infection with fungus belonging to the genus Trichophyton, Microsporum, Epidermophyton]) confirmed diagnoses of DSO of the target toenail affecting ≥25% to ≤60% of the target toenail as determined through clinimetric measurement.
  • Signed written informed consent form (ICF) prior to any trial related activity (subjects must have the mental, literate, and legal ability to give a written informed consent, which must comply with the ICH GCP guidelines and local requirements).
  • Subjects must be willing and able to comply with trial requirements.
  • Females must be either postmenopausal for ≥1 year (ie 12 consecutive months of amenorrhea, for which there is no other obvious pathologic or physiologic cause), or surgically sterile (tubal ligation, hysterectomy, or bilateral oophorectomy) for at least 6 months or, if of childbearing potential must use either highly effective birth control methods such as:
  • Oral, intravaginal or transdermal oestrogen- and progestogen-containing hormonal contraception associated with inhibition of ovulation
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  • Oral, injectable or implantable progestogen-only hormonal contraception associated with inhibition of ovulation
  • Intrauterine device or intrauterine hormone-releasing system
  • Bilateral tubal occlusion
  • Vasectomised partner provided that the partner is the sole sexual partner and that the vasectomised partner has received medical assessment of the surgical success Clinical Study Protocol
  • Sexual abstinence, ie, refraining from heterosexual intercourse during the entire period of risk associated with the trial treatments
  • OR
  • Acceptable birth control methods such as:
  • Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action
  • Male or female condom with or without spermicide
  • Cap, diaphragm or sponge with spermicide
  • A combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods) are also considered acceptable birth control methods
  • while using trial medication and 28 days after last dose of IMP.
  • Birth control methods which are considered unacceptable: Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method. Female condom and male condom should not be used together.
  • Treatment with the IMP will be discontinued in case of pregnancy.
  • The criteria with respect to pregnancy and contraception are in line with the CTFG Recommendations, v1.1, Sept 2020.

Who cannot join

  • Any other form of OM except DSO.
  • Nails with clinical evidence of no or low distal growth.
  • DSO of the target toenail where involvement has extended into the proximal portion of the target nail (unaffected proximal nail is ≤3mm) or nail matrix. Any severe OM defined as 3 or more affected toes on one foot.
  • Estimated target toenail thickness >3mm.
  • Presence of dermatophytoma (defined as thick masses of fungal hyphae and necrotic keratin between the nail plate and nail bed) on the target nail.
  • History of dermatophyte infections unresponsive to systemic or topical anti-fungal drugs (other than OM).
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  • Presence of toenail infection that does not involve a dermatophyte.
  • Presence of toenail infection that involves a non-dermatophyte fungus or yeast in combination with a dermatophyte, where the non-dermatophyte is, in the opinion of the Investigator, considered to be causative of OM based on clinical appearance, medical history or lifestyle risk.
  • Topical treatment with an antifungal medication within 12 weeks before Randomisation/Visit 2 (with the exception of up to 2 weeks' treatment during the screening period with a non-terbinafine topical antifungal to treat clinically active TP).
  • Other exclusion criteria
  • Systemic use of anti-fungal treatment within 12 months before Randomisation/Visit 2.
  • Past use within the last 6 months before Randomisation/Visit 2 or planned use of laser therapy, photodynamic therapy, chemical, surgical, relevant mechanical removal for OM or debridement.
  • Concomitant clinically suspected active TP at Randomisation/Visit 2.
  • Known allergy or known intolerabilities to any of the tested treatment products.
  • Subjects with diabetes, immune suppression, peripheral vascular disease, lymphatic insufficiency, recurrent cellulitis, or other compromised states of health whether due to underlying medical disorders or to long-term immunosuppressive treatments (including >4 weeks systemic corticoids or >4 weeks topical corticoids on the feet). Topical immunosuppressive treatment if not on the target nail is allowed.
  • Females of childbearing potential with a positive serum pregnancy test at Screening/Visit 1 and/or a positive urine pregnancy test at Randomisation/Visit 2 are excluded.
  • Women of childbearing potential who are pregnant or breast feeding or who plan to become pregnant after enrolment until 28 days after the last dose of IMP.
  • Subjects previously randomised in this trial or received BB2603 previously.
  • Use of any investigational agent during the study or within 28 days or 5 half-lives prior to Randomisation/Visit 2, whichever is longer.
  • Close affiliation with the Investigator (eg, a close relative) or persons working at a trial site, or subject who is an employee of the Sponsor's company.
  • Subjects who are institutionalised because of legal or regulatory order.
  • Hepatic impairment with AST or ALT >5 x Upper Limit of Normal.
  • Estimated creatinine clearance using Cockcroft-Gault formula and actual body weight <30 ml/min.
  • Presence of any other condition or infection of the foot or nail or other disease process that might affect the safety and well-being of the subject or confound the treatment evaluation (eg, psoriasis, lichen planus, or other medical conditions known to induce nail changes, trauma, previous toenail surgery with any residual disfigurement or any dermatological or nail condition that could mimic the signs and symptoms of OM, signs of severe peripheral circulatory insufficiency, use of chronic immunosuppressive medication or radiation therapy within 2 months prior to trial entry or planned during the trial period, immunocompromised).
  • Subjects deemed to be at risk of re-infection or recurrence of OM due to occupational, environmental or behavioural lifestyle in the opinion of the Investigator.
  • Any other significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in this trial, or may influence the result of the trial, or the subject's availability to participate in the trial.
  • Any known or suspected hypersensitivity to, or known allergy to, or other intolerability to BB2603 or its active ingredient or excipients.

Trial locations and contacts

20 sites in 3 countries.

20 sites in 3 countries

Poland12 sites
  • NZOZ Dermal

    Bialystok

  • NZOZ Osteo-Medic

    Bialystok

  • Klinika Dermatologii, Wenerologii

    Gdansk

  • Centrum Medyczne Angelius Provita

    Katowice

  • Gyncentrum Osrodek Badan Klinicznych

    Katowice

  • ETG Lodz

    Lodz

  • Etg Lublin Kunickiego

    Lublin

  • ETG Siedlce

    Siedlce

  • Laser Clinic

    Szczecin

  • ETG Warszawa

    Warsaw

  • dermMedica

    Wroclaw

  • ETG Zamość

    Zamość

Other trials in Poland

Germany6 sites
  • Licca Clinical Research Institute

    Augsburg

  • Praxis Dr. med. Thomas Wildfeuer & Kolleg*innen

    Berlin

  • Hautzentrum Jahrhunderthaus Gemeinschaftspraxis Dres. Niesmann und Othlinghaus

    Bochum

  • Uniklink Carl Gustav Carus, Klinik und Polyklinik für Dermatologie

    Dresden

  • Hautarztpraxis Dres. Leitz

    Stuttgart

  • Centroderm GmbH

    Wuppertal

Other trials in Germany

Czechia2 sites
  • Dermatovenerologická klinika VFN

    Prague

  • Sanatorium prof. Arenbergera

    Prague

Other trials in Czechia

About this study

Official title: A Multi-Centre, International, Randomised, Vehicle Controlled, Parallel-Group, Double-Blinded Phase 2 Trial of BB2603 Topical Treatment in Subjects With Distal Subungual Onychomycosis (DSO) of the Toenail

This study will be a multicenter, international, randomized, vehicle-controlled, parallel-group, double-blinded study. Subjects who are eligible to participate with a confirmed diagnosis of Distal Subungual onychomycosis (DSO) of the toenail will be randomized and participate in one of the following treatment groups: BB2603-1: 0.01% terbinafine/0.03% polyhexanide formulation, or BB2603-3: 0.03% terbinafine/0.09% polyhexanide formulation, or BB2603-10: 0.1% terbinafine/0.3% polyhexanide formulation, or Vehicle: 0.3% polyhexanide/20% ethanol/water formulation. The subject in each treatment group will be treated twice daily (BID) for 12 weeks and then complete a 28-day post-treatment visit.

Read the detailed description

Onychomycosis (OM; fungal nail infection) is a common and contagious fungal infection of the nail plate or nail bed, leading to the gradual destruction of the nail plate. OM is considered the most prevalent of the nail ailments, accounting for about 50% of all diseased nails and about 30% of cutaneous fungal infections. The prevalence of OM is reported to be 23% across Europe, 13.8% in North America and approximately 10% in Japan, with the prevalence increasing in Western countries, presumably due to lifestyle changes and the ageing of the population.

Distal subungual onychomycosis (DSO) is the most common form of OM, characterised by invasion of the nail bed and underside of the nail plate beginning at the hyponychium. This infection is visualised as nails with normal surface texture and thickness but variable "bays" of white nail that extend from the distal nail tip proximally into the area of the nail bed. The vast majority of cases of OM are caused by dermatophyte fungi. In 80% to 98% of affected individuals, Trichophyton rubrum with additional infections caused by Trichophyton mentagrophytes var interdigitale (commonly referred to as Trichophyton mentagrophytes) or Epidermophyton floccosum. The dermatophyte Trichophyton rubrum is the major cause of tinea pedis (TP; athlete's foot) and OM. OM is a progressive disease; if left untreated, OM can lead to permanent nail damage and associated discomfort.

Onychomycosis is currently treated with surgery, medical devices (eg laser therapy), oral or topical anti-fungal agents or a combination of both. Oral terbinafine, when used for a minimum of 3 months, can achieve an efficacy of 38% or higher if treatment is extended but has a significant drug-interaction and side effect profile, including liver failure, and periodic monitoring (after 4-6 weeks of treatment) of liver function test is recommended. Topical agents are used for up to 18 months but have significantly lower efficacy rates of less than 20%.

Terbinafine is a well-established synthetic allylamine anti-fungal developed by Sandoz (now Novartis) and commercially available worldwide for more than 25 years in different oral and topical formulations as a dermal cream (1%), emulsion gel (1%), solution/spray (1%), as well as oral tablets (250 mg and 125 mg). It is highly hydrophobic in nature and tends to accumulate in skin, nails, and fatty tissues. Terbinafine's anti-fungal mechanism of action is by inhibition of squalene epoxidase in the fungal cell membrane. This leads to a deficiency in ergosterol and an intracellular accumulation of squalene, resulting in fungal cell rupture/lysis (fungicidal activity).

Dermatophytoses of nails, in contrast to those at other body sites, are particularly difficult to eradicate with drug treatment. This is the consequence of factors intrinsic to the nail (the hard, protective nail plate, sequestration of pathogens between the nail bed and plate, and slow growth of the nail). The unique barrier properties of the nail plate, which hampers the passage of anti-fungal drugs in a concentration required to eradicate the deeply-seated causative fungi in the nail bed, is a specific challenge.

As such, there is a recognized need for a simple, effective and curative topical treatment for OM. Furthermore, topical treatment may result in minimal adverse systemic events and possibly improved adherence.

Being tested
BB2603-1, BB2603-3, BB2603-10, Vehicle
Keywords
DSO, Fungual Infection, Fungus, Nail
Medical subject headings
Mycoses, Onychomycosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BB2603-1Drug

    Treatment with topical spray twice-daily (BID) BB2603-1: 0.01% terbinafine

  • BB2603-3Drug

    Treatment with topical spray twice-daily (BID) BB2603-3: 0.03% terbinafine

  • BB2603-10Drug

    Treatment with topical spray twice-daily (BID) BB2603-10: 0.1% terbinafine

  • VehicleOther

    Treatment with topical spray twice-daily (BID): 0.3% polyhexanide/ 20% ethanol/ water formulation.

Study groups in NCT04188574
Study groupRoleWhat they receive
BB2603-10ExperimentalTreatment with topical spray twice-daily (BID) BB2603-10: 0.1% terbinafine
Receives: Drug: BB2603-10; Other: Vehicle
BB2603-3ExperimentalTreatment with topical spray twice-daily (BID) BB2603-3: 0.03% terbinafine
Receives: Drug: BB2603-3; Other: Vehicle
BB2603-1ExperimentalTreatment with topical spray twice-daily (BID)BB2603-1: 0.01% terbinafine
Receives: Drug: BB2603-1; Other: Vehicle
Vehicle ControlOther0.3% polyhexanide/ 20% ethanol/ water formulation.
Receives: Drug: BB2603-1; Drug: BB2603-3; Drug: BB2603-10; Other: Vehicle

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of subjects with an Early Response for BB2603-10 versus vehicle

    Early Response is defined as clinimetrically assessed clear nail growth (yes/no) and/or negative dermatophyte culture (yes/no).

    Measured: 16 weeks

Secondary outcomes (7)
  1. Number of subjects with a Complete Cure for BB2603-10 versus vehicle

    Complete Cure is assessed programmatically and is defined as satisfying the following: binary (yes/no) completely clear nail and mycological response (negative KOH and negative dermatophyte culture).

    Measured: 52 weeks

  2. Number of subjects with Completely Clear Nail, Almost Clear Nail, Negative KOH or Negative Dermatocyte Culture, assessed separately, for BB2603-10 versus vehicle

    Completely Clear Nail (yes/no), Almost Clear Nail (yes/no), Negative KOH (yes/no) and Negative Dermatocyte Culture (yes/no) are each assessed separately

    Measured: 52 weeks

  3. Concentration of terbinafine in the plasma in all subjects

    Terbinafine, the active component of BB2603, will be measured in pg/ml

    Measured: 52 weeks

  4. Number of subjects with adverse events

    Safety and tolerability data will be assessed by number of subjects with adverse events (AEs), serious adverse events, drug discontinuations due to AEs, and deaths. Data will be assessed at Week 16, 24 and 28 .

    Measured: 16, 24, 28 weeks

  5. Number of subjects with an Early Response for BB2603-1 or BB2603-3, respectively versus vehicle

    Early Response is defined as clinimetrically assessed clear nail growth (yes/no) and/or negative dermatophyte culture (yes/no).

    Measured: 16 weeks

  6. Number of subjects with a Complete Cure for BB2603-1 or BB2603-3, respectively versus vehicle

    Complete Cure is assessed programmatically and is defined as satisfying the following: binary (yes/no) completely clear nail and mycological response (negative KOH and negative dermatophyte culture).

    Measured: 52 weeks

  7. Number of subjects with Completely Clear Nail, Almost Clear Nail, Negative Dermatocyte Culture or Negative Dermatophyte Culture, assessed separately for BB2603-1 or BB2603-3, respectively versus vehicle

    Completely Clear Nail (yes/no), Almost Clear Nail (yes/no), Negative KOH (yes/no) and Negative Dermatocyte Culture (yes/no) are each assessed separately

    Measured: 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Dec 2019
  2. Study start22 Mar 2021
  3. Primary completion6 Dec 2022
  4. Study completion28 Jun 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Double-Blinded
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
111 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04188574
Sponsor's protocol ID
BBTAF202
Status last verified
Jul 2023
First submitted
16 Sep 2019
Last updated
1 Aug 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BB2603-1, BB2603-3 and BB2603-10 in people with Distal Subungual Onychomycosis and Fungal Infection, run by Blueberry Therapeutics at 20 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Poland, Germany, Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of subjects with an Early Response for BB2603-10 versus vehicle (time frame: 16 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2023.

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