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Mepolizumab in Nasal Polyposis

Primary Purpose

Nasal Polyps

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Mepolizumab

Placebo

Run In Medication

About this trial

This is an interventional treatment trial for Nasal Polyps focused on measuring Quality of Life, Intranasal Steroids, Severe Nasal Polyposis, Polyp Relapse, Endoscopic Polyp Score, Surgery

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion:

A subject will be eligible for inclusion in this study only if all of the following criteria apply:

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.
Subjects must have had at least one previous surgery for the removal of nasal polyps.
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.
Male or female between 18 and 70 years of age, inclusive at time of signing informed consent.
BMI within the range 19.0 to 31.0 kg/m2 (inclusive).
Subjects must be free of any clinically significant disease that would interfere with the study schedule or procedures or compromise his/her safety.
Subjects with concurrent asthma must be maintained on no more than 10mg/day of Prednisolone or the equivalent.
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.
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.
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.
Subjects are willing and available to complete the study and all measurements.
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:

As a result of medical interview, physical examination, or screening investigation the physician responsible considers the subject unfit for the study.
Subjects requiring oral corticosteroids at a dose greater than 10mg Prednisolone or equivalent during the study will be terminated from the study.
Subjects who have had an asthma exacerbation requiring admission to hospital within 4 weeks of Screening.
Subjects who have received immunotherapy within the previous 12 months.
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.
Subjects with a known medical history of Hepatitis B, Hepatitis C, or HIV infection.
Subjects with a history or suspicion of drug abuse or alcohol abuse within the last 6 months.
Subjects who are currently receiving, or have received within 3 months prior to first mepolizumab dose, chemotherapy, radiotherapy or investigational medications/therapies.
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
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.
Subjects with a history of allergic reaction to anti-IL-5 or other antibody therapy.
Pregnant females as determined by positive serum pregnancy test at screening or positive urine pregnancy test prior to each dosing occasion.
Breastfeeding/Lactating females.
Subjects who currently smoke or have smoked in the last 6 months.
Subjects who are unwilling or unable to follow the procedures outlined in the protocol.

Sites / Locations

GSK Investigational Site
GSK Investigational Site
GSK Investigational Site
GSK Investigational Site
GSK Investigational Site
GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Other

No Intervention

Arm Label

Treatment Periods 1-8

Run In period

Treatment periods 9-13

Arm Description

Part A comprises eight outpatient visits (Visits 1 - 8). For six of these visits, subjects will receive a dose of either 750 mg mepolizumab or placebo. Dosing occurs in four week intervals. Assessment for entry into Part B will take place at the last visit in Part A (Visit 8). Subjects not eligible for Part B will have study exit procedures performed and be discontinued.

10-14 day run in period to assess the patients suitability for entry into Part A of the trial.

Subjects eligible for Part B will attend the clinic for up to 5 more outpatient visits (Visits 9 - 13) for assessments. Visits occur every four weeks. There is no dosing in Part B. At the point when each subject meets Study Exit criteria, study exit procedures will be performed and the subject will exit the study.

Outcomes

Primary Outcome Measures

Number of Participants With a Reduced Need for Surgery at Week 25

Assessment of the nasal polyposis condition was performed after six months of dosing to determine the situation indicative of a reduction in the need for surgery. The components used to determine the need for surgery were endoscopic polyp (ENP) scores and a severity of condition as measured by a visual analogue scale (VAS). Surgery was still deemed required for a participant with an ENP score of >=3, or an ENP score of 2 and a VAS symptom score of >7. The number of participants with reduced need for polyp surgery are presented as missing data set to non-responders (NR) and missing data last observation carry forward (LOCF). LOCF is defined as missing responses at Week 25 imputed with the last non-missing post-dose observation for that participant.

Secondary Outcome Measures

Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Each nostril was assessed for polyps and graded at Weeks 1, 2, 5, 9, 13, 17, 21, and 25. The right and left nostrils were scored from 0 to 4, where, 0 = No polyps; 1 = Small polyps in the middle meatus not reaching below the inferior border of the middle concha; 2 = Polyps reaching below the lower border of the middle turbinate; 3 = Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle concha; and 4 = Large polyps causing complete obstruction/congestion of the inferior meatus. The ENP score was recorded for both the right and the left nostril. The higher of the two scores was derived and used for the analysis. The ENP score ranges from 0 to 4, with a higher score indicating a larger polyp.

Number of Participants Who Required Polyp Surgery at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Assessment of the nasal polyposis condition was performed after 6 months of dosing to determine the situation indicative of a reduction in the need for surgery. The components used to determine the need for surgery were endoscopic polyp scores and a severity of condition as measured by a VAS. Surgery was required for participants with ENP scores of >=3, or ENP scores of 2 and a VAS symptom score of >7.

Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 2, 5, 9, 13, 17, 21, and 25

SBP and DBP were measured at Baseline (Week 1) and at Weeks 2, 5, 9, 13, 17, 21, and 25. Baseline is defined as the Week 1 pre-dose assessment. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value.

Mean Change From Baseline in Pulse Rate at Weeks 2, 5, 9, 13, 17, 21, and 25

Pulse rate was measured at Baseline (Week 1) and at Weeks 2, 5, 9, 13, 17, 21, and 25. Baseline is defined as the Week 1 pre-dose assessment. Change from Baseline is defined as the difference between the post-dose post-Baseline visit value and the Baseline value.

Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

A single safety 12-lead ECG was performed using a standard 12-lead ECG machine at Weeks 1, 2, 5, 9, 13, 17, 21, and 25. Any abnormal clinically significant (CS) and not clinically significant (NCS) findings were identified. ECG abnormaility with respect to CS and NCS findings were judged by the investigator or appropriately qualified designee. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Absolute Values of Clinical Chemistry Parameters Including Blood Urea Nitrogen (BUN), Glucose Fasting, Chloride, Sodium, Potassium, Carbon Dioxide, and Calcium at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

BUN, glucose fasting, chloride, sodium, potassium, carbon dioxide (CO2), and calcium were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

Absolute Values of the Clinical Chemistry Parameters of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), and Gamma Glutamyltransferase (GGT) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

ALT, AST, ALP, and GGT were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

Absolute Values of the Clinical Chemistry Parameters of Albumin and Protein at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Albumin and protein were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

Absolute Values of the Clinical Chemistry Parameters of Total and Direct Bilirubin, Creatinine (CRT), and Uric Acid (UA) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Total bilirubin (TB) and direct bilirubin (DB), creatinine, and uric acid were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

Absolute Values of the Hematology Parameters of Platelet Count and White Blood Cell (WBC) Count, Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Platelet count, WBC count, basophils, eosinophils, lymphocytes, monocytes, and neutrophils were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

Absolute Values of the Hematology Parameters of Hemoglobin and Mean Corpuscular Hemoglobin Concentration (MCHC) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Hemoglobin and MCHC were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

Absolute Values of the Hematology Parameter of Red Blood Cell (RBC) Count and Reticulocyte Count (RC) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

RBC count and RC were assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

Absolute Values of the Hematology Parameter of Mean Corpuscular Hemoglobin (MCH) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

MCH was assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

Absolute Values of the Hematology Parameter of Mean Corpuscular Volume (MCV) at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

MCV was assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

Absolute Value of the Hematology Parameter of Reticulocyte Count/Erythrocyte Uncorrected at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Reticulocyte count was assessed at Week 1 pre-dose, Week 2, Week 5 pre-dose, Week 9 pre-dose, Week 13 pre-dose, Week 17 pre-dose, Week 21 pre-dose, and Week 25 (4 Weeks post last dose).

Number of Participants With Positive Clinically Relevant Urinalysis Results at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Specific gravity, power of hydrogen (pH), glucose, protein, blood, and ketones were assessed at Weeks (Wk) 1, 2, 5, 9, 13, 17, 21, and 25. Results for all urinalysis parameters were assessed for clinical relevance by physician. Clinically relevant positive results are presented. Clinically relevant positive results are defined as those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Number of Participants With Any Treatment-emergent Adverse Event (AE) and Serious Adverse Event (SAE)

An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is an important medical event that jeopardizes the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or is associated with liver injury and impaired liver function.

Mean of the Forced Expiratory Volume in 1 Second (FEV1) at Weeks 2, 5, 9, 13, 17, 21, and 25

FEV1 is defined as the volume of air forcefully expelled from the lungs in one second. FEV1 measurements were taken by spirometry at each clinic visit. FEV1 was calculated as the maximum of three readings taken at each time point for each participant. Spirometry data is plotted and analyzed using a repeated measures model to calculate treatment difference, confidence intervals and p-values.

Mean of Forced Vital Capacity (FVC) at Weeks 2, 5, 9, 13, 17, 21, and 25

FVC is defined as the maximum amount of air that can forcibly be blown out after a maximum inspiration. FVC was calculated as the maximum of three readings taken at each time point for each participant. Spirometry data are plotted and analyzed using a repeated measures model to calculate treatment difference, confidence intervals and p-values.

Mean Peak Expiratory Flow Rate (PEFR) at Indicated Weeks 2, 5, 9, 13, 17, 21, and 25

PEFR is defined as the maximum airflowrate generated during a forced expiration beginning with the lungs fully inflated. PEFR was calculated as the maximum of three readings taken at each time point for each participant. Spirometry data is plotted and analyzed using a repeated measures model to calculate treatment difference, confidence intervals and p-values.

Individual Symptoms Visual Analogue Scale (VAS) Scores at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Participants were asked to indicate on a VAS (0 to 10 centimeters) the severity of nasal polyposis and its four symptoms (one VAS for each symptom): rhinorrhea; mucus in the throat; nasal blockage; loss of smell. The left-hand side of the scale (0) represents "not troublesome," and the right hand side of the scale (10) represents "worst possible troublesome." Hence the score ranges between 0 to 10, with higher scores indicating greater severity.

Mean Peak Nasal Inspiratory Flow (PNIF) at Weeks 2, 5, 9, 13, 17, 21, and 25

Participants used a portable hand-held inspiratory flow meter to measure and record PNIF in the morning prior to taking the study medication. Three measurements were taken, and the largest measurement was recorded in the electronic diary. PNIF data is plotted and analyzed using a repeated measures model to calculate treatment difference, confidence intervals and p-values.

Olfaction Testing: Worst Nostril Score (WNS) and Mean Nostril Score (MNS) at Weeks 2, 5, 9, 13, 17, 21, and 25

Sniffin'Sticks were used to assess each participant's sense of smell (olfaction). Olfaction testing results were recorded for both the right and left nostrils The worst nostril score (number of correct answers for the worst nostril) and the mean nostril score (mean number of correct answers across both nostrils) were recorded. Scores range from 0 to 12 (high score indicating normal olfactory sensation). Olfaction data are plotted and analyzed using a repeated measures model to calculate treatment difference, confidence intervals and p-values.

Sino-Nasal Outcome Test (SNOT)-22 Questionnaire Total Score at Week 25 (Adjusted for Week 1 Baseline)

SNOT-22 questionnaire is a modification of the SNOT-20 and contains the questions (ques) related to smell and nasal obstruction. Each ques is graded with a numerical score for each response (resp); scores range from 0 for "no symptoms" to 5 for "as bad as things could be." Scores for each of the ques is summed to derive the total score for that par. at that visit. If the par. did not complete any ques at a visit, then he/she were not to have any missing values imputed, and his/her total score for that visit was set to missing. If a par. had some missing scores (but no more than 50% missing at that visit), then scores for the missing resp were imputed as the mean of the non-missing resp for that par. at that visit. The SNOT-22 total score ranges from 0 to 110, with higher scores representing a worse quality of life. Questionnaire data analysis was done using an ANCOVA to obtain the LS-means, treatment difference and confidence interval at Week 25, adjusting for Week 1 Baseline scores.

Index Score of the EuroQoL Quality of Life-5D (EQ-5D) Questionnaire at Week 25 (Adjusting for Week 1 Baseline Scores)

The EQ-5D is a standardized, 2-part questionnaire used to measure health outcomes. The first part contains descriptions of the following five components: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Responses to each of the five domains are measured on a 3-point scale (1-no problems, 2-some problems, and 3-severe problems). An index for the descriptive scores was derived using the general European weights, obtained for each of the countries in this study. Index scores were derived for each participant at each time point by taking sum of weights. Index score ranges from -0.718 to 1, with lower scores indicating poor health. ANCOVA model with treatment, Baseline (Week 1 scores) and country as factors was used to calculate treatment difference and confidence intervals at Week 25.

VAS Score of the EQ-5D Questionnaire at Week 25 (Adjusting for Week 1 Baseline Scores)

The EQ-5D is a standardized, 2-part questionnaire used to measure health outcomes. The second part of the questionnaire is a VAS question, requiring the participant to self rate his/her health score on a scale of 0 (worst imaginable health state) to 100 (best imaginable health state). ANCOVA model with treatment, Baseline (Week 1 scores) and country as factors was used to calculate treatment difference and confidence intervals at Week 25.

Systemic Clearance of Mepolizumab 750 mg

Blood samples were collected for the assessment of systemic clearance at Weeks 1, 2, 5, 9, 13, and 25. Systemic Clearance (CL) is estimated using a population-Pharmacokinetic model incorporating all available data points from all participants. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.

Volume of Distribution of Mepolizumab 750 mg

Volume of distribution at steady-state was derived from pharmacokinetic parameter estimates of a population pharmacokinetic model. Blood samples were collected for analysis of volume of distribution at Weeks 1, 2, 5, 9, 13, and 25. All available concentrations at all available datapoints from all participants were incorporated into the model. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.

Bodyweight-adjusted Clearance

Clearance is the volume of plasma that would contain the amount of drug excreted per day. Blood samples were collected for the assessment of bodyweight-adjusted clearance at Weeks 1, 2, 5, 9, 13, and 25. Clearance was estimated using a population-pharmacokinetic model incorporating all available data points from all participants. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.

Steady-State Volume of Distribution

Steady-state volume of distribution is the blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces. Blood samples were collected for the assessment of steady-state volume of distribution at Weeks 1, 2, 5, 9, 13, and 25. Steady-state volume of distribution was estimated using a population-pharmacokinetic model incorporating all available data points from all participants. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.

Maximum Observed Plasma Drug Concentration (Cmax), Average Concentration (Cav[0-inf]), and Steady State Maximum Observed Plasma Drug Concentration (Cmax SS)

Blood samples were collected for the assessment of Cmax, Cav(0-inf), and Cmax SS at Weeks 1, 2, 5, 9, 13, and 25. These parameters were estimated using a population-pharmacokinetic model incorporating all available data points from all participants. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.

Area Under the Plasma Drug Concentration Versus Time Curve From Time 0 Extrapolated to Infinite Time (AUC[0-inf])

Blood samples were scheduled to be collected for the assessment of AUC(0-inf) at Weeks 1, 2, 5, 9, 13, and 25 AUC[0-inf] is derived from individual systemic clearance estimates using the expression AUC[0-inf] = Dose/CL. Hence all data are incorporated into the estimation of CL and by implication AUC[0-inf].

Half-life (Alpha) and Half-life (Beta)

Half-life (Alpha) is the rate of decline in plasma concentrations due to the process of drug redistribution from the central to the peripheral compartment and half-life (Beta ) is the rate of decline due to the process of drug elimination due to metabolism. Blood samples were collected for the assessment of half-life (Alpha) and half-life (Beta) at Weeks 1, 2, 5, 9, 13, and 25. Half-life was estimated using a population-pharmacokinetic model incorporating all available data points from all participants. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.

Pharmacokinetic/Pharmacodynamic (PK/PD) Model Derived Baseline

Blood samples were collected for the assessment of PK/PD model derived Baseline at Weeks 1, 2, 5, 9, 13, 17, 21 and 25. An exploratory Emax direct response model was fitted to serial blood eosinophil count data (including placebo) using model-predicted mepolizumab concentrations (with zero imputed for placebo treated participants). All available blood eosinophil count data were incorporated into the model. Individual values were estimated from the model as post-hoc values after incorporating between-participant variability.

PK/PD Model Derived Coefficient of Variation of Baseline (CV[Baseline]), Variation of Maximal Effect of Drug (CV[Emax]), and Residual

A residual is the difference between the observed and predicted values. Blood samples were collected for the assessment of PK/PD model derived CV(Baseline), CV(Emax), and residual at Weeks 1, 2, 5, 9, 13, 17, 21 and 25. An exploratory Emax direct response model was fitted to serial blood eosinophil count data (including placebo) using model-predicted mepolizumab concentrations (with zero imputed for placebo treated subjects). All available datapoints were incorporated into the model. Individual values are estimated from the model as post-hoc values after incorporating between-participant variability.

PK/PD Model Derived Half Maximal Effective Drug Concentration (EC50)

Blood samples were collected for the assessment of PK/PD model derived EC50 at Weeks 1, 2, 5, 9, 13, 17, 21 and 25. An exploratory Emax direct response model was fitted to serial blood eosinophil count data (including placebo) using model-predicted mepolizumab concentrations (with zero imputed for placebo treated participants). All available datapoints were incorporated into the model. Individual values are estimated from the model as post-hoc values after incorporating between-partcipant variability.

PK/PD Model Derived Maximum Inhibition

Blood samples were collected for the assessment of Maximum Inhibition at Weeks 1, 2, 5, 9, 13, 17, 21 and 25. An exploratory Emax direct response model was fitted to serial blood eosinophil count data (including placebo) using model-predicted mepolizumab concentrations (with zero imputed for placebo treated participants). All available datapoints were incorporated into the model. Individual values are estimated from the model as post-hoc values after incorporating between-participant variability.

Number of Participants With Positive Immunogenicity (Anti-mepolizumab Antibody Testing)

Blood samples were collected at Week 1 pre-dose, Week 5 pre-dose, Week 13 pre-dose and Week 25 (4 weeks post last dose) for anti-mepolizumab antibody testing using a validated electrochemiluminescent (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'.

Full Information

NCT ID

NCT01362244

First Posted

May 26, 2011

Last Updated

March 16, 2021

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT01362244

Brief Title

Mepolizumab in Nasal Polyposis

Official Title

A Randomised, Double-Blind, Placebo Controlled, Multi-Center Study To Investigate The Use Of Mepolizumab (Sb-240563) In Reducing The Need For Surgery In Subjects With Severe Bilateral Nasal Polyposis

Study Type

Interventional

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Completed

Study Start Date

May 12, 2009 (Actual)

Primary Completion Date

December 5, 2014 (Actual)

Study Completion Date

December 5, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed Description

Nasal polyposis has long been known as chronic inflammatory disease of the nasal mucosa. This disease is characterized by the presence of polyps in the upper nasal cavity, originating from within the ostiomeatal complex. The presence of polyps can cause long-term symptoms such as prominent nasal obstruction, post-nasal drip, loss of smell, and discharge. These symptoms can impact greatly upon a patient's quality of life.The etiology of nasal polyposis is currently unknown. The aim of this present study is to investigate the use of mepolizumab in reducing the potential need for surgery in subjects with severe bilateral nasal polyposis. The study is split into two parts: Part A is the treatment phase and focuses on the reduction of the need for surgery by exploring the efficacy of six doses of mepolizumab (one dose every four weeks) on nasal polyposis. This dosing regime will build upon the previous PoC study by exploring the potential for increased clinical efficacy as assessed by the potential need for surgery, and also and increased duration of action as assessed by time to relapse. Part B is the follow-up phase and will assess post-treatment nasal polyposis dynamics with a focus on time to relapse. All subjects participating in this study will undergo a run-in period on a low dose of intranasal steroids (INS) prior to first dosing. INS will be continued throughout the study up until study exit. This is to reflect the real life circumstances in which mepolizumab is intended to be used as a therapy. The overall aim of the study design is to further assess the impact in the potential need for surgery and explore an appropriate mepolizumab therapeutic regimen strategy for the treatment of nasal polyposis. In this study, the assessment of nasal polyposis will be performed by means of combining endoscopic polyp score with subject reported symptoms. This approach reflects real-life clinical assessment of nasal polyposis. Also, this study incorporates condition specific and general medical questionnaires in order to obtain a better understanding of the impact of severe nasal polyposis of the subject's quality of life (QOL). This is in line with increasing focus in the medical field on the effects of medical conditions and treatments on the quality of life of patients (Fokkens et al 2007).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nasal Polyps

Keywords

Quality of Life, Intranasal Steroids, Severe Nasal Polyposis, Polyp Relapse, Endoscopic Polyp Score, Surgery

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

109 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment Periods 1-8

Arm Type

Experimental

Arm Description

Arm Title

Run In period

Arm Type

Other

Arm Description

10-14 day run in period to assess the patients suitability for entry into Part A of the trial.

Arm Title

Treatment periods 9-13

Arm Type

No Intervention

Arm Description

Intervention Type

Drug

Intervention Name(s)

Mepolizumab

Intervention Description

750 mg of mepolizumab by IV infusion

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo by IV infusion

Intervention Type

Drug

Intervention Name(s)

Run In Medication

Intervention Description

subjects will undergo a run-in period of 10 - 14 days on a low dose of Intranasal Steroids (INS).

Primary Outcome Measure Information:

Title

Number of Participants With a Reduced Need for Surgery at Week 25

Description

Time Frame

Week 25

Secondary Outcome Measure Information:

Title

Number of Participants With Endoscopic Nasal Polyp (ENP) Score Dynamics at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Description

Time Frame

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Title

Number of Participants Who Required Polyp Surgery at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Description

Time Frame

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Title

Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Weeks 2, 5, 9, 13, 17, 21, and 25

Description

Time Frame

Baseline and Weeks 2, 5, 9, 13, 17, 21, and 25

Title

Mean Change From Baseline in Pulse Rate at Weeks 2, 5, 9, 13, 17, 21, and 25

Description

Time Frame

Baseline and Weeks 2, 5, 9, 13, 17, 21, and 25

Title

Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Description

Time Frame

Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Title

Absolute Values of Clinical Chemistry Parameters Including Blood Urea Nitrogen (BUN), Glucose Fasting, Chloride, Sodium, Potassium, Carbon Dioxide, and Calcium at Weeks 1, 2, 5, 9, 13, 17, 21, and 25

Description

Time Frame