Mepolizumab in Nasal Polyposis

NCT01362244 | Completed Phase 2 Results DMC

• 2 other identifiers: 1117822008-003772-21
• Study Type: interventional
• Target: 109
• Locations: 3 countries
• Sites: 6

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.

Conditions

Nasal Polyps

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Week 25

Secondary Outcomes (38)

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

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

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

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

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

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

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

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

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

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

Study Arms (3)

Treatment Periods 1-8

EXPERIMENTAL

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.

Drug: Mepolizumab; Drug: Placebo

Run In period

OTHER

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

Drug: Run In Medication

Treatment periods 9-13

NO INTERVENTION

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.

Interventions

Mepolizumab DRUG

750 mg of mepolizumab by IV infusion

Treatment Periods 1-8

Placebo DRUG

Placebo by IV infusion

Treatment Periods 1-8

Run In Medication DRUG

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

Run In period

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (6)

GSK Investigational Site

Ghent, 9000, Belgium

Location

GSK Investigational Site

Amsterdam, 1105 AZ, Netherlands

Location

GSK Investigational Site

Cambridge, United Kingdom

Location

GSK Investigational Site

London, EC1M 6BQ, United Kingdom

Location

GSK Investigational Site

London, SW3 6NP, United Kingdom

Location

GSK Investigational Site

London, WC1X 8DA, United Kingdom

Location

Related Publications (2)

• Bachert C, Sousa AR, Lund VJ, Scadding GK, Gevaert P, Nasser S, Durham SR, Cornet ME, Kariyawasam HH, Gilbert J, Austin D, Maxwell AC, Marshall RP, Fokkens WJ. Reduced need for surgery in severe nasal polyposis with mepolizumab: Randomized trial. J Allergy Clin Immunol. 2017 Oct;140(4):1024-1031.e14. doi: 10.1016/j.jaci.2017.05.044. Epub 2017 Jul 4.

  PMID: 28687232 BACKGROUND

• Chong LY, Piromchai P, Sharp S, Snidvongs K, Webster KE, Philpott C, Hopkins C, Burton MJ. Biologics for chronic rhinosinusitis. Cochrane Database Syst Rev. 2021 Mar 12;3(3):CD013513. doi: 10.1002/14651858.CD013513.pub3.

  PMID: 33710614 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Nasal Polyps

Interventions

mepolizumab; Jogging; Dosage Forms

Condition Hierarchy (Ancestors)

Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Polyps; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Running; Locomotion; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise; Motor Activity; Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques

Limitations and Caveats

Part B was removed due to the low numbers of participants enrolling into Part B. GSK determined it was no longer feasible to achieve a meaningful number of participants and therefore recruitment into this portion of the study was stopped.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2011
• First Posted: May 30, 2011
• Study Start: May 12, 2009
• Primary Completion: December 5, 2014
• Study Completion: December 5, 2014
• Last Updated: April 12, 2021
• Results First Posted: March 28, 2016

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share

Locations

BE (1); NL (1); GB (4)