Mepolizumab in Nasal Polyposis
Condition: Nasal Polyps
MeSH terms: Nasal Polyps
Intervention: Mepolizumab; Placebo; Run In Medication
Intervention description: 750 mg of mepolizumab by IV infusion; Placebo by IV infusion; subjects will undergo a run-in period of 10 - 14 days on a low dose of Intranasal Steroids (INS).
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 109.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Quality of Life; Intranasal Steroids; Severe Nasal Polyposis; Polyp Relapse; Endoscopic Polyp Score; Surgery

Summary:

      A two-part, randomised, double-blind, placebo controlled, multi-centre study to investigate
      the use of mepolizumab (SB-240563) in reducing the need for surgery in subjects with severe
      bilateral nasal polyposis.
    

Eligibility criteria:

        Inclusion:

        A subject will be eligible for inclusion in this study only if all of the following
        criteria apply:

          1. Subjects have a diagnosis of severe bilateral nasal polyposis at the screening visit
             and Visit 1 (i.e. at end of run-in period) which meets the definition of the situation
             indicative of the need for surgery as described in Decision Table 1 in Appendix 3.

          2. Subjects must have had at least one previous surgery for the removal of nasal polyps.

          3. Subjects must have an history of refractory response to steroid therapy as shown by
             being deemed potentially eligible for surgery despite having been on a
             regular/continuous course of nasal corticosteroids for the treatment of nasal
             polyposis for at least 3 months and/or have received a short course of oral steroids
             in the past for nasal polyp treatment.

          4. Male or female between 18 and 70 years of age, inclusive at time of signing informed
             consent.

          5. BMI within the range 19.0 to 31.0 kg/m2 (inclusive).

          6. Subjects must be free of any clinically significant disease that would interfere with
             the study schedule or procedures or compromise his/her safety.

          7. Subjects with concurrent asthma must be maintained on no more than 10mg/day of
             Prednisolone or the equivalent.

          8. Female subjects of childbearing potential must agree to use one of the contraception
             methods listed in Section 8.1. This criterion must be followed from 1 month prior to
             first dose of study medication until four months after last dose of study medication.

             Females of non -childbearing potential are defined as pre-menopausal females with a
             documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of
             spontaneous amenorrhea. Females on hormone replacement therapy (HRT) and whose
             menopausal status is in doubt will be required to use one of the contraception methods
             in Section 8.1 if they wish to continue their HRT during the study (from 1 month prior
             to first dose of study medication until four months after last dose of study
             medication). Otherwise, they must discontinue HRT to allow confirmation of
             post-menopausal status prior to study enrollment. For most forms of HRT, at least 2- 4
             weeks will elapse between the cessation of therapy and the blood draw; this interval
             depends on the type and dosage of HRT. Following confirmation of their post-menopausal
             status, they can resume use of HRT during the study without use of a contraceptive
             method.

          9. Male subjects must agree to use one of the contraception methods listed in Section
             8.1. This criterion must be followed from the time of the first dose of study
             medication until four months after last dose of study medication.

         10. Subjects are capable of giving written informed consent, which includes agreeing to be
             compliant with the study requirements and restrictions listed in the consent form.

         11. Subjects are willing and available to complete the study and all measurements.

         12. Subjects are capable of reading, comprehending, and writing the local language at a
             sufficient level to complete study related materials.

        Exclusion:

        A subject will not be eligible for inclusion in this study if any of the following criteria
        apply:

          1. As a result of medical interview, physical examination, or screening investigation the
             physician responsible considers the subject unfit for the study.

          2. Subjects requiring oral corticosteroids at a dose greater than 10mg Prednisolone or
             equivalent during the study will be terminated from the study.

          3. Subjects who have had an asthma exacerbation requiring admission to hospital within 4
             weeks of Screening.

          4. Subjects who have received immunotherapy within the previous 12 months.

          5. Subjects with a positive pre-study drug/alcohol screen. A minimum list of drugs that
             will be screened for include amphetamines, barbiturates, cocaine, opiates,
             cannabinoids and benzodiazepines.

          6. Subjects with a known medical history of Hepatitis B, Hepatitis C, or HIV infection.

          7. Subjects with a history or suspicion of drug abuse or alcohol abuse within the last 6
             months.

          8. Subjects who are currently receiving, or have received within 3 months prior to first
             mepolizumab dose, chemotherapy, radiotherapy or investigational medications/therapies.

          9. Subjects with one or more of the following abnormal laboratory values:

               -  Serum creatinine ≥ 3 times institutional ULN

               -  AST or/ALT ≥ 5 times institutional ULN

               -  Platelet count < 50,000/μL

         10. Subjects 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
             subjects are acceptable.

         11. Subjects with a history of allergic reaction to anti-IL-5 or other antibody therapy.

         12. Pregnant females as determined by positive serum pregnancy test at screening or
             positive urine pregnancy test prior to each dosing occasion.

         13. Breastfeeding/Lactating females.

         14. Subjects who currently smoke or have smoked in the last 6 months.

         15. Subjects who are unwilling or unable to follow the procedures outlined in the
             protocol.