Resumen

La poliposis nasal (PN) ha sido reconocida desde hace tiempo como una enfermedad inflamatoria crónica de la mucosa nasal. Esta enfermedad se caracteriza por la presencia de pólipos en la cavidad nasal superior, originados en el complejo ostiomeatal. La presencia de pólipos puede causar síntomas a largo plazo como obstrucción nasal prominente, goteo posnasal, pérdida del olfato y rinorrea. Mepolizumab (SB240563) es un anticuerpo monoclonal humanizado de tipo Inmunoglobulina G1 [IgG1], kappa, que bloquea la unión de la interleucina-5 humana (hIL-5) al complejo receptor de interleucina-5 (IL-5) expresado en la superficie de los eosinófilos, inhibiendo así la señalización. Se ha demostrado que la neutralización de IL-5 con mepolizumab reduce los eosinófilos en sangre, esputo y tejidos, por lo que se considera una opción de tratamiento en diversas enfermedades eosinofílicas, incluida la PN. El objetivo de este estudio de fase 3 (FaseIII) aleatorizado, doble ciego, de grupos paralelos es evaluar la eficacia clínica y la seguridad de mepolizumab 100 miligramos (mg) subcutáneo (SC) como tratamiento adyuvante al tratamiento de mantenimiento en adultos con PN bilateral grave. El estudio incluirá un período de rodaje de 4 semanas seguido de una aleatorización a un período de tratamiento de 52 semanas. Los participantes recibirán mepolizumab 100 mg o placebo SC administrado por el investigador o su delegado mediante una jeringa de seguridad precargada cada 4 semanas durante 52 semanas. A lo largo de todo el período del estudio (rodaje + período de tratamiento + seguimiento), los participantes recibirán el tratamiento estándar (SoC) para PN, que consiste en spray nasal diario de furoato de mometasona (MF) y, si se requiere, lavados nasales con solución salina, ciclos cortos ocasionales de corticosteroides orales (OCS) a dosis altas y/o antibióticos. El período de tratamiento constará de trece dosis de mepolizumab o placebo administradas cada 4 semanas. Además, hasta los primeros 200 participantes aleatorizados serán seguidos cada dos meses durante hasta 6 meses adicionales después de la Visita 15 (7 meses después de la última dosis) con el fin de evaluar el mantenimiento de la respuesta y validar un modelo fisiológico derivado del estudio previo de Fase 2. Aproximadamente 400 participantes serán aleatorizados (200 participantes por brazo de tratamiento) en el estudio. La duración total del estudio será de 76 semanas para los primeros 200 participantes aleatorizados y de 52 semanas para el resto de los participantes que no participen en el seguimiento de 6 meses sin tratamiento.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

years of age and older inclusive, at the time of signing the informed consent.
Body weight greater or equal to 40 kilogram (kg).
Male or female participants (with appropriate contraceptive methods) to be eligible for entry into the study. To be eligible for entry into the study, woman of childbearing potential (WOCBP) must commit to consistent and correct use of an acceptable method of birth control from the time of consent, for the duration of the trial, and for 105 days after last study drug administration.
Participants who have had at least one previous surgery in the previous 10 years for the removal of NP. NP Surgery is defined as any procedure involving instruments with resulting incision (cutting open) and removal of polyp tissue from the nasal cavity (polypectomy). For the purpose of inclusion into this study, any procedure involving instrumentation in the nasal cavity resulting in dilatation of the nasal passage such as balloon sinuplasty, insertion of coated stents or direct injection of steroids or other medication without any removal of NP tissue is not accepted.
Participants with bilateral NP as diagnosed by endoscopy or computed tomography (CT) scan.
Presence of at least two of the following symptoms one of which should be either nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip) and either nasal discharge (anterior/posterior nasal drip); facial pain/pressure; reduction or loss of smell for at least 12 weeks prior to screening.
Participants with severe NP symptoms defined as an obstruction VAS symptom score of \>5.
Severity consistent with a need for surgery as described by:
Participants with an overall VAS symptom score \>7,
Participants with an endoscopic bilateral NP score of at least 5 out of a maximum score of 8 (with a minimum score of 2 in each nasal cavity).
Treatment with intranasal corticosteroids (INCS) for at least 8 weeks prior to screening.

Criterios de exclusión

As a result of medical interview, physical examination, or screening investigation, the physician responsible considers the participant unfit for the study.
Cystic fibrosis
Eosinophilic granulomatosis with polyangiitis (also known as churg strauss syndrome), young's, kartagener's or dyskinetic ciliary syndromes.
Antrochoanal polyps
Nasal septal deviation occluding one nostril
Acute sinusitis or upper respiratory track infection (URTI) at screening or in 2 weeks prior to screening
Ongoing rhinitis medicamentosa (rebound or chemical induced rhinitis)
Participants who have had an asthma exacerbation requiring admission to hospital within 4 weeks of Screening.
Participants who have undergone any intranasal and/or sinus surgery (for example polypectomy, balloon dilatation or nasal stent insertion) within 6 months prior Visit 1.
Participants where NP surgery is contraindicated in the opinion of the Investigator.
Participants with a known medical history of human immunodeficiency virus (HIV) infection.
Participants with a known, pre-existing parasitic infestation within 6 months prior to Visit 1.
Participants who are currently receiving, or have received within 3 months (or 5 half lives - whatever is the longest) prior to first mepolizumab dose, chemotherapy, radiotherapy or investigational medications/therapies.
Participants with a history of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK medical monitor, contraindicates their participation. Aspirin-sensitive participants are acceptable.
Participants with a history of allergic reaction to anti-IL-5 or other monoclonal antibody therapy.
Participants on a waiting list for NP surgery while at screening
Participants that have taken part in previous mepolizumab, reslizumab, dupilumab or benralizumab studies.
Use of systemic corticosteroids (including oral corticosteroids) or corticosteroid nasal solution (intranasal corticosteroid is accepted) within 4 weeks prior to Screening or planned use of such medications during the double-blind period.
INCS dose changes within 1 month prior to screening.
Treatments with biological or immunosuppressive treatment (other than omalizumab) treatment within 5 terminal phase half lives of Visit 1.
Omalizumab treatment in the 130 days prior to Visit 1.
Commencement of leukotriene antagonist treatment less than 30 days prior to Visit 1.
Allergen immunotherapy within the previous 3 months.
Women who are pregnant or lactating or are planning on becoming pregnant during the study.
Participants who currently smoke or have smoked in the last 6 months.
Any participant who is considered unlikely to survive the duration of the study period or has any rapidly progressing disease or immediate life-threatening illness (e.g. cancer). In addition, any participant who has any other condition (e.g. neurological condition) that is likely to affect respiratory function should not be included in the study.
Participants who have known, pre-existing, clinically significant endocrine, autoimmune, cardiovascular, metabolic, neurological, renal, gastrointestinal, hepatic, hematological or any other system abnormalities that are uncontrolled with standard treatment.
Immunocompromized, other than that explained by the use of corticosteroids taken as therapy.
A current malignancy or previous history of cancer in remission for less than 12 months prior to Screening. Participants with successfully treated basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ, with no evidence of recurrence may participate in the study.
Current active liver or biliary disease (with the exception of gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment).
Corrected QT interval (QTc) \>450 milliseconds (msec) or QTc \>480 msec in participants with bundle branch block at visit 1.
A known or suspected history of alcohol or drug abuse within 2 years prior to Screening (Visit 1) that in the opinion of the investigator would prevent the participant from completing the study procedures.
An investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the aforementioned that is involved in this study.
In the opinion of the investigator, any participant who is unable to read and/or would not be able to complete a questionnaire.

Intervenciones

drug

Mepolizumab

Mepolizumab injection 100 mg/millilitre (mL) is a clear to opalescent, colorless to pale yellow to pale brown sterile solution for SC injection in a single-use, safety syringe.

drug

Placebo

Placebo is a clear to opalescent, colorless sterile solution for SC injection in a single-use, safety syringe.

drug

Mometasone furoate

All participants will receive mometasone furoate usually 400 micrograms (mcg), 2 actuations (50 mcg/actuation) in each nostril twice daily. Intolerant participants will use 200g (2 actuations \[50 g/actuation\] in each nostril once daily).

Ubicaciones

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Florida, Buenos Aires, Argentina

GSK Investigational Site

La Plata, Buenos Aires, Argentina

GSK Investigational Site

Mar del Plata, Buenos Aires, Argentina

GSK Investigational Site

Rosario, Santa Fe Province, Argentina

GSK Investigational Site

Buenos Aires, Argentina

GSK Investigational Site

Buenos Aires, Argentina

GSK Investigational Site

Buenos Aires, Argentina

GSK Investigational Site

Mendoza, Argentina

GSK Investigational Site

Mendoza, Argentina

GSK Investigational Site

San Miguel de Tucumán, Argentina

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Mepolizumab

Placebo

Mometasone furoate

Ubicaciones

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

GSK Investigational Site

Patrocinadores