Moderate to severe nasal polyposis MedDRA version: 19.0 Level: PT Classification code 10028756 Term: Nasal polyps System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Code: AK001
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: AK001 drug product (DP)
Current Sponsor code: AK001 drug product (DP)
Concentration unit: mg/ml mill
Sponsors
Allakos, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients are eligible for the study if all of the following criteria are met: 1. Written informed consent 2. Male and female patients aged =18 and =75 years at the time of Screening 3. SNOT-22 =30 4. At Screening, TPS of =5 for both nostrils with presence on endoscopy of nasal polyps of grade =2 in each nostril according to the polyp grading scale Polyp grading scale for each nostril: 0=no nasal polyps 1=small polyps in the middle meatus not reaching below the inferior border of the middle turbinate 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 turbinate 4=large polyps causing complete obstruction of the inferior nasal cavity 5. History of at least 2 of the following symptoms for more than 4 weeks prior to Screening: a) Anterior nasal discharge b) Posterior nasal discharge c) Nasal congestion, blockade, or obstruction d) Decreased sense of smell e) Facial pain or pressure 6. Received continuous topical nasal steroids and/or leukotriene receptor antagonists for at least 8 weeks prior to Screening unless failure or no effect of prior nasal steroid or leukotriene receptor antagonist therapy is documented 7. At randomization, received =80% of doses of NASONEX scheduled during the Run-in period 8. At randomization, TPS of =5 for both nostrils with presence on endoscopy of nasal polyps of grade =2 in each nostril according to the polyp grading scale (see Inclusion Criterion #4) and despite prior INS treatment during the Run-in period 9. Female patients must be post-menopausal for =1 year with documented follicle-stimulating hormone (FSH) >30 IU/L, surgically sterile (tubal ligation, hysterectomy, or bilateral oophorectomy) for at least 3 months, or, if of child-bearing potential, willing to use a highly effective method of contraception from Screening until at least 3 months after the last dose of the study drug was administered, which corresponds to approximately 5 half-lives of the study drug 10. Male patients with female partners of childbearing potential must agree to use a highly effective method of contraception from Screening until at least 3 months after the last dose of the study drug was administered, which corresponds to approximately 5 half-lives of the study drug. All fertile men with female partners of childbearing potential should be instructed to contact the Investigator immediately if they suspect their partner might be pregnant (e.g., missed or late menstrual period) at any time during study participation. 11. Negative Screening ova and parasite test 12. No clinically significant Screening 12-lead ECG, vital sign, hematology, chemistry, or urinalysis findings 13. Able to comply with all study procedures including recording scores of symptoms (i.e., anterior nasal discharge; posterior nasal discharge, nasal congestion, blockade, or obstruction; decreased sense of smell; facial pain or pressure) at clinic visits Additional Sub-study Inclusion Criteria: 1. Written informed consent to participate in the sub-study 2. Able to comply with all sub-study requirements (procedures and clinic visits) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: Patients are ineligible for the study if any of the following criteria are met: 1. Use of systemic corticosteroids within 6 weeks prior to Screening (or 5 half-lives, whichever is longer) or scheduled to receive systemic corticosteroids 2. Chronic use of antibiotic therapy within 3 months prior to Screening 3. Receipt of short-term antibiotic therapy within 14 days prior to Screening or use of antibiotics during the Screening period 4. Nasal surgery (including polypectomy) within 6 months prior to Screening 5. Significant mechanical nasal airway obstruction due to septal deviation based on Investigator assessment 6. Use of investigational drugs or participation in another clinical trial within 30 days prior to Screening or 5 half lives, whichever is longer 7. Use of any medications that may interfere with the study, such as immunosuppressive drugs during the 2 weeks before Screening, or expected to require such medications through Day 112 8. Pregnancy or lactation in women 9. In patients with comorbid asthma, either of the following: a) A FEV1 =60% at Screening b) An asthma exacerbation requiring systemic (oral and/or parenteral) steroid treatment or hospitalization for >24 hours for treatment of asthma within 30 days prior to Screening 10. History of human immunodeficiency virus infection or other severe immunosuppressive disease 11. Current diagnosis or prior history of allergic fungal sinusitis, cystic fibrosis, ciliary dyskinesia, Wegener’s Granulomatosis, or Churg-Strauss syndrome 12. Current diagnosis or prior history of any other condition likely to present with non eosinophilic nasal polyps
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the effect of each of 2 different dose levels of AK001 separately in combination with an intranasal steroid (INS) versus the INS alone on the reduction in size of nasal polyps as evaluated by the change from Baseline to Week 12 after the start of treatment in Total Polyp Score (TPS);Primary end point(s): Total Polyp Score (TPS): Change from Baseline to Week 12;Timepoint(s) of evaluation of this end point: Screening, Day -3, Day 21, Day 49, Day 84, Day 112;Secondary Objective: 1. To evaluate the effect of each of 2 different dose levels of AK001 separately in combination with an INS versus the INS alone on changes from Baseline to Week 12 after the start of treatment in: a) Size of polyps as evaluated by Lund-Mackay score at selected sites by CT scan b) Nasal airway patency as evaluated by peak nasal inspiratory flow (PNIF) c) Ability to smell by the UPSIT Test d) Patient-reported symptoms of sinusitis (Sino-nasal Outcome Test-22 [SNOT-22] and Visual Analogue Scales [VASs]) e) Clinical Symptoms improvement scale f) Quality of life (Short Form Health Survey [SF-36]) 2. To evaluate the time to first response in TPS 3. To evaluate the change in TPS, UPSIT, and patient-reported symptoms of sinusitis over time 4. To evaluate the safety and tolerability of each of 2 different dose levels of AK001 separately in combination with an INS during 7 weeks of study drug in patients with moderate to severe nasal polyps and whose symptoms are resistant to INSs | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Size of polyps as evaluated by Lund-Mackay score at selected sites by CT scan • Nasal airway patency as evaluated by PNIF • UPSIT • SNOT-22 (patient-reported symptoms) • VASs (patient-reported symptoms) • clinical symptoms improvement scale • SF-36 (quality of life) • Blood eosinophil and basophil absolute counts The following specific additional efficacy endpoints will be evaluated in patients with comorbid asthma: • TPS by blinded centralized evaluation of endoscopy • Pulmonary function (FEV1, FVC, and FEF) assessed using spirometry • ACT • Use of asthma rescue therapy Pharmacokinetic endpoints: Blood samples obtained from the arm that is not used for the study drug infusion will be obtained pre-dose on Days 0, 21, and 49 and on Days 14, 84, and 112 for PK analyses. Serum concentrations of AK001 will be measured using a validated enzyme-linked immunosorbent assay (ELISA) method. Safety endpoints: • TEAEs • Withdrawals from study due to AEs • Vital sign findings • Laboratory test (including anti-drug antibody [ADA]) findings • Concomitant medication use • Physical examination (PE) findings;Timepoint(s) of evaluation of this end point: • Size of polyps as evaluated by Lund-Mackay score by CT scan: Days -3, 84, 112 • PNIF: Days 0, 21, 84, 112 • UPSIT: Days 0, 14, 21, 49, 84, 112 • SNOT-22: Screening, Days 0, 14, 21, 49, 84, 112 • VASs: Screening, Run-in, Days -3, 0, 14, 21, 49, 84, 112 • SF-36: Days 0, 21, 49, 84, 112 • Blood eosinophil and basophil absolute counts: Screening, Days -3, 14, 21, 49, 84, 112 • Pulmonary function (FEV1, FVC, and FEF) assessed using spirometry: Screening, Days 21, 49 • ACT: Screening, Days 0, 21, 49, 84, 112 • Use of asthma rescue therapy: Screening, Run-in, Days -3, 0, 14, 21, 49, 84, 112 • Pharmakokinetics: Days 0, 14, 21, 49, 84, 112 • Safety: various timepoints | — |
Countries
Belgium, Germany, Netherlands, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Trials Information
Allakos, Inc.
Outcome results
None listed