Resumen

Este es un estudio de 16 semanas, aleatorizado, doble ciego, controlado con placebo, de grupos paralelos y multicéntrico, para evaluar la eficacia y seguridad de OPN-375 186 µg dos veces al día (BID) en adolescentes con poliposis nasal bilateral, seguido de una fase de tratamiento abierto de 12 semanas. El número total planificado de sujetos es de aproximadamente 72 adolescentes (de 12 a 17 años) que serán asignados aleatoriamente para recibir 1 de 2 tratamientos del estudio en una proporción 2:1 (OPN-375 186 µg: placebo). Para el subestudio de farmacocinética, se incluirán hasta 14 sujetos para obtener 10 que lo completen.

Descripción detallada

El objetivo principal de este estudio es evaluar la eficacia de la administración intranasal de OPN-375 186 µg dos veces al día (BID) versus placebo en adolescentes con poliposis nasal bilateral y congestión nasal, analizando la reducción de los síntomas de congestión/obstrucción nasal al final de la semana 4, medida por las puntuaciones promedio de los síntomas matutinos instantáneos en el diario de 7 días, y la reducción del grado total de pólipos a la semana 16, determinada por la puntuación de una escala de graduación de gravedad de 0 a 6 puntos.

Elegibilidad

Edad mínima: 12 YearsEdad máxima: 17 YearsSexo: ALL

Criterios de inclusión

Male or female subjects aged 12 to 17 years, inclusive, at time of Visit 1 (Screening).
Female subjects, if sexually active, must,
be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method \[e.g., condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel\], or male partner sterilization) before entry and throughout the study, or
be surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), or
be abstinent.
All female subjects not documented to be infertile (e.g., infertility due to congenital abnormality or surgical sterilization) must have a negative serum or urine beta-human chorionic gonadotropin (hCG) at Visit 1 (Screening) and a negative urine pregnancy test at the Visit 2 (Day 1/Randomization/Baseline).
Must have bilateral nasal polyposis with a grade of 1 to 3 in each of the nasal cavities as determined by a nasal polyp grading scale score measured by nasoendoscopy at Visit 1 (Screening).
Must report at least mild symptoms of nasal congestion/obstruction as demonstrated by an average morning nasal congestion/obstruction score of at least 1.0 over a 7 day period during the single-blind run-in period. (Subjects not meeting this inclusion criterion may be re-screened once after at least 4 weeks.)
Subjects with comorbid asthma must be stable, defined as no exacerbations (e.g., no emergency room visits, hospitalization, or oral or parenteral steroid use) within the 3 months before Visit 1 (Screening). Subjects who received inhaled corticosteroids are required to be on no more than a moderate dosage regimen as defined by 2015 Global Initiative for Asthma Guidelines (GINA) for 1 month before Visit 1 (Screening) and to be expected to remain on it throughout the study (GINA 2015). Subjects receiving inhaled fluticasone alone or in combination may not participate in the PK sub-study.
Must be able to cease treatment with intranasal medications including, but not limited to, intranasal oxymetazoline or any other decongestants, intranasal antihistamines, intranasal steroids, intranasal sodium cromolyn, nasal atropine, nasal ipratropium bromide, inhaled corticosteroids (except permitted doses listed above for asthma) at Visit 1 (Screening). \[Note: intranasal antibiotics and saline are permissible\]
If taking oral antihistamines, must be on a stable regimen for at least 2 weeks prior to Visit 1 (Screening), and agree to not change the dose of these medications until after Visit 3 (Week 4) of the study.
Subjects (with assistance from parent or legal guardian if needed) must demonstrate the ability to complete the daily diary during the run-in period to be eligible for randomization.
Must demonstrate correct use of the demo EDS.
Must be capable, in the opinion of the investigator, of providing assent and the appropriate parent(s) or guardian must provide an informed consent to participate in the study.
Have received mepolizumab (Nucala®), reslizumab (Cinquair®), dupilumab (Dupixent®), omalizumab (Xolair®), or benralizumab (Fasenra™) within 6 months of Visit 1
Have nasal or oral candidiasis
Have taken a potent CYP3A4-inhibitor within 14 days before Visit 1 (Screening)
Any serious or unstable concurrent disease, psychiatric disorder, or any significant concomitant medical condition that, in the opinion of the investigator could confound the results of the study or could interfere with the subject's participation or compliance in the study, or pose a specific risk to the subject due to study participation
History or current diagnosis of any form of glaucoma or ocular hypertension (i.e., \>21 mm Hg)
History of intraocular pressure elevation on any form of steroid therapy
Current diagnosis of the presence (in either eye) of a cataract of Grade 1 or greater as defined on the Eye Examination Worksheet OR, less than a Grade 1 cataract with associated visual impairment
A recent (within 1 year of Visit 1 \[Screening\]) history of drug or alcohol abuse or dependence
Positive urine drug screen at screening visit for stimulants, opioids, or cocaine
Have participated in an investigational drug clinical trial within 30 days of Visit 1 (Screening)
Parents, guardian or caregivers of the subject who are employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.

Criterios de exclusión

Pregnancy or lactation
Has a history of cystic fibrosis
Have used XHANCE (fluticasone propionate) nasal spray within the past 2 months
Inability to achieve bilateral nasal airflow for any reason, including nasal septum deviation
Inability to examine both nasal cavities for any reason, including severe nasal septum deviation
Have known history of nasal septum erosion, ulceration or perforation, or evidence of such lesion on Visit 1 (Screening) nasal examination/nasoendoscopy
Other significant nasal pathology or abnormal anatomy
Has had any episode of epistaxis with frank bleeding in the 3 months before Visit 1 (Screening)
History of more than 5 sinus or nasal surgeries for either nasal polyps or nasal/sinus inflammation (lifetime)
Have had any surgery on the nasal septum
History of sinus or nasal surgery within 6 months before Visit 1 (Screening)
History of any surgical procedure that prevents the ability to accurately diagnose or grade polyps
Current, ongoing rhinitis medicamentosa (rebound rhinitis)
Have significant oral structural abnormalities (e.g., a cleft palate)
History of Churg-Strauss syndrome or dyskinetic ciliary syndromes
Purulent nasal infection (recent fever or symptoms of lethargy), acute sinusitis, or upper respiratory tract infection within 2 weeks before Visit 1 (Screening). Potential subjects presenting with one of these infections may be rescreened after 4 weeks.
Have an allergy, hypersensitivity, or contraindication to corticosteroids or steroids
Have a hypersensitivity to any excipients in the study drug

Ubicaciones