Clinical trial NCT06616922: Assessment of the Effects and Tolerability of RD03/2016 for the Treatment of Bacterial Conjunctivitis in Adults
Official title: Assessment of the Effects and Tolerability of RD03/2016 (Levofloxacin; Ketorolac Trometamol 0.5+0.5% w/v Eye Drops Solution) for the Treatment of Bacterial Conjunctivitis in Adults: a Multicentre, Randomized, Blinded-assessor, Phase II Non Inferiority Study - MIRAKLE
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Conjunctivitis, Bacterial
Keywords: RD03/2016
Levofloxacin
Lead sponsor: NTC srl
Sponsor class: INDUSTRY
First posted: 2024-09-27
Enrollment: 252
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, parallel-group, blinded-assessor study
Primary purpose: TREATMENT

Brief summary: This is a phase II, randomized, parallel-group, blinded-assessor, multicentre study to assess the non-inferiority of RD03/2016 eye drops vs. levofloxacin eye drops alone (1:1) in microbiological eradication in patients with a clinical diagnosis of bacterial conjunctivitis with moderate/severe signs.

Detailed description: This study will enroll 252 patients with clinical diagnosis of acute bacterial conjunctivitis with moderate/severe signs (score ≥ 2 for each cardinal sign, i.e., bulbar conjunctival injection, palpebral conjunctival injection and conjunctival discharge).

Enrolled patients will attend three study visits: baseline (Day 0), On-Therapy (OT; Day 3-4) and final visit (Day 7-9). The duration of the study for each patient will be 7-9 days.

Enrolled patients will undergo the following assessments: anamnesis; ophthalmological examination; swab of the lower conjunctiva for bacteriological examination, and a urine pregnancy test (for women of childbearing potential). Patients will be provided with a study smartphone to take photographs of the affected eye at home. Photographs will be taken by the person (a relative or a caregiver) assisting the patient and uploaded on the server of the study eCRF through eyePRO.net.

Test product (i.e. RD03/2016 - Levofloxacin; Ketorolac Trometamol 0.5+0.5% w/v eye drops solution) is the first fixed dose association between a quinolone antibiotic (i.e. levofloxacin) highly effective on the pathogenic bacteria that most frequently cause eye infections, and a nonsteroidal anti-inflammatory drug (NSAID) (i.e. ketorolac) highly effective in the control of signs and symptoms associated with inflammation.

The dosage proposed for RD03/2016 is one drop 4 times a day for 5 days, lower than that currently approved for levofloxacin alone. In patients with clinical diagnosis of bacterial conjunctivitis and in presence of moderate/severe signs and symptoms requiring an anti-inflammatory treatment for rapid symptomatic improvement, the use of RD03/2016 compared to treatment with levofloxacin alone could lead to a substantial simplification of the therapeutic regimen, without changing the rate of microbiological eradication.

Eligibility criteria: Inclusion Criteria:

1. Ability of patient to consent and provide signed written informed consent
2. Male or female aged ≥ 18 year.
3. Clinical diagnosis of acute bacterial conjunctivitis with moderate/severe signs (score ≥ 2 for each cardinal signs, i.e. bulbar conjunctival injection, palpebral conjunctival injection and conjunctival discharge, in at least one eye), not previously treated with antibiotics, steroids and nonsteroidal anti-inflammatory drugs (NSAIDs).
4. Able and willing to follow study procedures.
5. Availability of a person (a relative or a caregiver) to be trained for the execution of the photographic documentation required by the study and for the use of eyePRO.net.
6. Willing to interrupt the use of contact lenses for the entire duration of the study.

Exclusion Criteria:

1. Any acute ocular clinical disease other than bacterial conjunctivitis.
2. Any ocular surgery (including laser treatment) in the study eye within 30 days prior to study entry.
3. Any ocular (in the study eye) or systemic antimicrobial agents administered concurrently or within 3 days prior to study entry.
4. Any ocular (in the study eye) or systemic steroids or NSAIDs administered concurrently.
5. Pathological conditions or treatments that in the opinion of the Investigator may interfere with the efficacy and/or safety evaluations of the study (e.g. chronic blepharitis, glaucoma, moderate-severe dry eye).
6. Participation in previous clinical studies if less than 5 half-lives of the Investigational Medicinal Product (IMP) used have passed.
7. Hypersensitivity to the products, other quinolones, acetylsalicylic acid and other NSAIDs (due to potential for cross-sensitivity), or their excipients.
8. Contraindications to ocular treatment with levofloxacin and/or ketorolac.
9. Pregnancy or breastfeeding. Women of childbearing potential must have a negative urine pregnancy test at baseline visit and practice effective contraceptive measures throughout the study.

Primary outcomes:
measure: Proportion of patients with microbiological eradication
timeFrame: At the Final visit (Day 7-9)
Secondary outcomes:
measure: By-pathogen microbiological eradication rate of levofloxacin-susceptible bacteria
timeFrame: At baseline that are eradicated at the final visit (Day 7-9)
measure: Overall per-patient microbiological eradication rate of bacteria intermediate or resistant to levofloxacin
timeFrame: At the final visit (Day 7-9)
measure: Overall by-pathogen microbiological eradication rate of bacteria intermediate or resistant to levofloxacin
timeFrame: At baseline that are eradicated at the final visit (Day 7-9)
measure: Proportion of patients with clinical cure
timeFrame: At Day 3-4 and final visit (Day 7-9)
measure: Time to clinical cure
timeFrame: Every 12 ± 1 hours from Day 0 to Day 7-9
measure: Time to resolution (absence) of bacterial conjunctivitis symptoms
timeFrame: Every 12 ± 1 hours from Day 0 to Day 7-9
Other outcomes:
measure: Safety: Adverse events throughout the study
timeFrame: Throughout the study, from Day 0 to Day 7-9
measure: Local tolerability: Ocular itching/burning or discomfort related to study drug instillation
timeFrame: Twice a day, from Day 0 to Day 5
measure: Compliance: Assessment of the number of instillations
timeFrame: From Day 1 to Day 5
measure: Feasibility: Microbiological eligibility rate
timeFrame: At the Final visit (Day 7-9)
measure: Feasibility: Patient confidence in using the study smartphone and eyePRO.net
timeFrame: At the Final visit (Day 7-9)
measure: Feasibility part 1: Assessment of the mean number of pictures uploaded at a time through eyePRO.net
timeFrame: At the Final visit (Day 7-9)
measure: Feasibility part 2: Assessment of the mean number of pictures uploaded at a time through
timeFrame: At the Final visit (Day 7-9)
measure: Feasibility part 3: Assessment of the mean number of pictures uploaded at a time through
timeFrame: At the Final visit (Day 7-9)
measure: Feasibility: Accuracy of photographic assessments of clinical cure against the gold standard direct ocular examination
timeFrame: At the Final visit (Day 7-9)
Locations:
city: Karlsruhe
country: Germany
facility: Städtisches Klinikum Karlsruhe Augenklinik
city: Bari
country: Italy
facility: A.O.U. Policlinico Consorziale di Bari
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII
city: Camaiore
country: Italy
facility: Ospedale della Versilia
city: Carrara
country: Italy
facility: Centro Polispecialistico Achille Sicari
city: Catania
country: Italy
facility: Presidio Ospedaliero G. Rodolico - A.O.U. "Policlinico - Vittorio Emanuele"
city: Chiari
country: Italy
facility: ASST Franciacorta - Ospedale di Chiari
city: Chieti
country: Italy
facility: Clinica Oftalmologica Ospedale SS Annunziata
city: Firenze
country: Italy
facility: Clinica Oculistica Azienda Ospedaliero-Universitaria Careggi di Firenze
city: Messina
country: Italy
facility: Clinica Oculistica Azienda Ospedaliero - Universitaria Policlinico "G. Martino"
city: Milano
country: Italy
facility: ASST Fatebenefratelli Sacco - Istituto Fatebenefratelli e Oftalmico
city: Milano
country: Italy
facility: ASST Fatebenefratelli Sacco
city: Milano
country: Italy
facility: ASST Santi Carlo e Paolo
city: Milano
country: Italy
facility: Clinica Oculistica Ospedale San Giuseppe
city: Milano
country: Italy
facility: Ospedale Maggiore Policlinico - U.O. Oculistica Fondazione IRCCS Ca' Granda
city: Milazzo
country: Italy
facility: Oculistica Ospedale G. Fogliani
city: Napoli
country: Italy
facility: U.O.S.C. Oculistica Az. Osp. di Rilievo Nazionale A. Cardarelli
city: Palermo
country: Italy
facility: A.O.U. Policlinico P. Giaccone
city: Palermo
country: Italy
facility: ARNAS Civico Di Cristina Benfratelli
city: Pisa
country: Italy
facility: Presidio Ospedaliero di Cisanello - Azienda Ospedaliero Universitaria Pisana
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario - IRCSS Agostino Gemelli
city: Roma
country: Italy
facility: IRCCS Fondazione G.B. Bietti
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Casa Sollievo della Sofferenza
city: Savigliano
country: Italy
facility: S.S. Annunziata di Savigliano
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese
city: Treviso
country: Italy
facility: Ospedale di Treviso, AULSS2 Treviso
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona
city: Ivanovo
country: Russian Federation
facility: Regional Budgetary Institution of Healthcare "Ivanovo Regional Clinical Hospital"
city: Moscow
country: Russian Federation
facility: Federal State Autonomous Institution "S.N. Fedorov National Medical Research Center "MNTK "Eye Microsurgery" of the Ministry of Health of the Russian Federation
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Educational Institution of High Professional Education "Moscow State Medical Stomatology University named after A.I.Evdokimov"
city: Moscow
country: Russian Federation
facility: State Budgetary Institution "National Medical Research Center for Eye Diseases named after Helmholts" of the Ministry of Healthcare of the Russian Federation
city: Omsk
country: Russian Federation
facility: State Budgetary Healthcare Institution of the Omsk Region "Clinical Ophthalmological Hospital named after V.P. Vykhodtsev"
city: Saint Petersburg
country: Russian Federation
facility: Private Institution of Healthcare "Clinical hospital "RR-Medicine" of the city of Saint-Petersburg"
city: San Pietroburgo
country: Russian Federation
facility: LLC Sphera-Med
city: Yaroslavl
country: Russian Federation
facility: State Budgetary Healthcare Institution of Yaroslavl Region "Clinical Hospital #2"
city: Madrid
country: Spain
facility: Sección De Cornea, Hospital Universitario La Paz
city: Marbella
country: Spain
facility: Ophthalmology Unit Empresa Pública Hospital Costa del Sol
city: Valencia
country: Spain
facility: Hospital La Fe Avenida de Fernando Abril Martorell
city: Valladolid
country: Spain
facility: Servicio De Oftalmología Hospital Universitario Rio Hortega
city: Vigo
country: Spain
facility: Servicio Oftalmología (Unidad Córnea Y Superficie Ocular) - Hospital do Meixoeiro Camino De Meixoeiro
Study officials:
affiliation: Ospedale San Raffaele IRCCS S.r.l.
name: Francesco Bandello, Prof.
role: PRINCIPAL_INVESTIGATOR
References: