WAYPOINT: Efficacy and Safety of Tezepelumab in Participants With Severe Chronic Rhinosinusitis With Nasal Polyposis

Sponsor

AstraZeneca (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04851964

Collaborator

Amgen (Industry)

400

Enrollment

135

Locations

Arms

42.1

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Multicentre, Randomised, Double-Blind, Parallel-Group, Placebo-Controlled Phase 3 Efficacy and Safety Study of Tezepelumab in Participants with Severe Chronic Rhinosinusitis with Nasal Polyposis

Condition or Disease	Intervention/Treatment	Phase
Chronic Rhinosinusitis With Nasal Polyps	Biological: Experimental: Tezepelumab Other: Placebo	Phase 3

Detailed Description

This is a multicentre, randomised, double-blind, placebo controlled, parallel group study designed to evaluate the efficacy and safety of tezepelumab in adults with severe, chronic rhinosinusitis with nasal polyposis. Approximately 400 subjects will be randomized globally. Subjects will receive tezepelumab, or placebo, administered via subcutaneous injection using the accessorized pre-filled syringe (APFS), over a 52-week treatment period. The study also includes a post-treatment follow-up period of 12-24 weeks for participants who complete the 52-week treatment period.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Double-Blind

Primary Purpose:

Treatment

Official Title:

A Multicentre, Randomised, Double-Blind, Parallel-Group, Placebo-Controlled Phase 3 Efficacy and Safety Study of Tezepelumab in Participants With Severe Chronic Rhinosinusitis With Nasal Polyposis (WAYPOINT)

Actual Study Start Date :

Apr 22, 2021

Anticipated Primary Completion Date :

Aug 2, 2024

Anticipated Study Completion Date :

Oct 25, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tezepelumab Tezepelumab subcutaneous injection, in an accessorized pre-filled syringe.	Biological: Experimental: Tezepelumab Tezepelumab subcutaneous injection Other Names: Tezepelumab
Placebo Comparator: Placebo Placebo subcutaneous injection, in an accessorized pre-filled syringe.	Other: Placebo Placebo subcutaneous injection

Arm

Intervention/Treatment

Experimental: Tezepelumab

Tezepelumab subcutaneous injection, in an accessorized pre-filled syringe.

Biological: Experimental: Tezepelumab

Tezepelumab subcutaneous injection

Other Names:

Tezepelumab

Placebo Comparator: Placebo

Placebo subcutaneous injection, in an accessorized pre-filled syringe.

Other: Placebo

Placebo subcutaneous injection

Outcome Measures

Primary Outcome Measures

Nasal Polyp Score [Baseline to Week 52]
Change from baseline in total Nasal Polyp Score at Week 52. The Nasal Polyp Score is the sum of the right and left nostril scores (maximum 8), as evaluated by nasal endoscopy.
Participant Reported Nasal Congestion [Baseline to Week 52]
Change from baseline in bi-weekly mean Nasal Congestion score evaluated as part of the Nasal Polyposis Symptom Diary at Week 52. Nasal Congestion Score is captured by asking participants to rate the severity of their worst nasal congestion over the past 24 hours (0-None; 1-Mild; 2-Moderate; 3-Severe).

Secondary Outcome Measures

Loss of Smell [Baseline to Week 52]
Change from baseline in bi-weekly mean loss of smell evaluated by the Nasal Polyposis Symptom Diary by asking patients to rate the severity of their worst difficulty with sense of smell over the past 24 hours at week 52. Response options include: 0- None; 1- Mild; 2- Moderate; 3- Severe.
Nasal Polyp-Quality of Life Compared with Placebo [Baseline to Week 52]
Change from baseline in SinoNasal Outcome Test 22 (SNOT-22) scores at Week 52.SinoNasal Outcome Test 22 scores are participant-reported and assess physical problems, functional limitations and emotional consequences of SinoNasal conditions. Patient-reported symptom severity and symptom impact over the past 2 weeks are captured via a 6-point scale (0-No Problem to 5-Problem as bad as it can be). The total score is the sum of item scores and has a range from 0 to 110 (higher scores indicate poorer outcomes).
Nasal Polyposis Surgery and/or Receiving Systemic Corticosteroids for Nasal Polyposis [Up to Week 52]
Time to surgery and/or systemic corticosteroids for nasal polyposis, time to nasal polyposis surgery, and time to systemic corticosteroids for nasal polyposis up to Week 52.
Sinus Opacification [Baseline to Week 52]
Change from baseline in Lund Mackay score evaluated by CT, sinus severity score by quantitative CT assessment, at Week 52. The Lund-Mackay score scoring system is used to provide a quantitative assessment of nasal sinuses on sinus CT scans. Based on the sinus CT images, the five sinuses (maxillary, anterior ethmoid, posterior ethmoid, sphenoid and frontal) on each site are score by central radiologist as follows: (0-Normal; 1-Partial Opacification; 2-Total Opacification). The osteomeatal complex is scored for right and left sides (0 - Not occluded; 2- Occluded). The total score ranges from 0 to 24 (higher scores indicate poorer outcomes).
Nasal Polyposis Symptom Diary Total Symptom Score [Baseline to Week 52]
Change from baseline in bi-weekly mean Nasal Polyposis Symptom Diary Total Symptom Score at Week 52. The participant will complete an 11-item nasal polyposis symptom diary each morning throughout the screening, treatment and followup periods. The participant is asked to consider their experience with nasal polyposis/nasal polyps over the past 24hrs when responding to each question. Participants are asked to report their experience with nasal polyposis symptoms (nasal blockage, nasal congestion, runny nose, postnasal drip (mucus drainage down the throat), headache, facial pain, facial pressure, difficulty with sense of smell) and symptom impacts (difficulty with sleeping due to nasal symptoms and difficulty with daily activities due to nasal symptoms). Participants report the severity of each symptom and symptom impact at its worst using a 4-point verbal rating scale (0-None to 3-Severe). A total symptom score is calculated by taking the sum of the 8 equally weighted symptom items.
Resolution/Near Complete Resolution of Nasal Polyps (defined as maximum NPS of 1 in each nostril) [At Week 52]
Proportion of participants who achieve a maximum NPS of 1 in each nostril at Week 52.
Resolution/Near Complete Resolution of Nasal Polyps (defined as maximum NPS of 1 in each nostril) and Nasal Polyposis Symptom Diary Total Symptom Score response [At Week 52]
Proportion of participants who achieve a maximum NPS of 1 in each nostril and Nasal Polyposis Symptom Diary Total Symptom Score response at Week 52.
Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) in Participants with Comorbid Asthma and Aspirin Exacerbated Respiratory Disease (AERD)/Nonsteroidal Anti-Inflammatory Drug Exacerbated Respiratory Disease (NSAID-ERD) [Baseline to Week 52]
Change from baseline in pre-bronchodilator forced expiratory volume in 1 second at Week 52. For participants with comorbid asthma and aspirin exacerbated respiratory disease (AERD)/nonsteroidal anti-inflammatory drug exacerbated respiratory disease (NSAID-ERD), difference in change from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1) in the tezepelumab arm as compared to placebo at Week 52. FEV1 is defined as the volume of air exhaled from the lungs in the first second of forced expiration.

Other Outcome Measures

Nasal Polyp Score [Baseline to Week 52]
Change from baseline over time in Nasal Polyp Score through Week 52. The Nasal Polyp Score is the sum of the right and left nostril scores (maximum 8), as evaluated by nasal endoscopy.
Nasal Polyp Score [Baseline to Week 52]
Proportion of participants with (i) ≥1 point reduction and (ii) ≥2 points reduction in the Nasal Polyp Score at Week 52. The Nasal Polyp Score is the sum of the right and left nostril scores (maximum 8), as evaluated by nasal endoscopy.
Participant Reported Nasal Congestion [Baseline to Week 52]
Change from baseline over time in bi-weekly mean Nasal Congestion Score evaluated by Nasal Polyposis Symptom Diary through Week 52. Nasal Congestion Score is captured by asking participants to rate the severity of their worst nasal congestion over the past 24 hours (0-None; 1-Mild; 2-Moderate; 3-Severe).
Loss of Smell [Baseline to Week 52]
Change from baseline in loss of smell evaluated by University of Pennsylvania Smell Identification Test (UPSIT) at Week 52. The University of Pennsylvania Smell Identification Test is a quantitative test of olfactory function which uses microencapsulated odorants that are released by scratching standardized odour-impregnated test booklets. Scores are based on number of correctly identified odours (score range 0-40).
Sinus Opacification [Baseline to Week 52]
Change from baseline in Modified Lund Mackay score evaluated by CT at Week 52. The Modified Lund-Mackay score scoring system is used to provide a semi-quantitative assessment of nasal sinuses on sinus CT scans. Based on the sinus CT images, the five sinuses (maxillary, anterior ethmoid, posterior ethmoid, sphenoid and frontal) on each site are score by central radiologist as follows: (0-0% Opacification; 1-1-25% Opacification; 2-26-50% Opacification; 3-51-75% Opacification; 4-76-99% Opacification; 5-100% Opacification). The osteomeatal complex is scored for right and left sides (0 - Not occluded; 2- Occluded). The maximum total Modified Lund Mackay score is 50, 54 when including the Osteomeatal complex score.
Systemic Corticosteroid Use [Over 52 weeks]
Exposure of systemic corticosteroids over 52 Weeks.
Nasal Polyposis Symptom Diary [Baseline to Week 52]
Change from baseline by domain of the Nasal Polyposis Symptom Diary through Week 52. The participant will complete an 11-item nasal polyposis symptom diary each morning throughout the screening, treatment and follow-up periods. The participant is asked to consider their experience with nasal polyposis/nasal polyps over the past 24 hours when responding to each question. Participants are asked to report their experience with nasal polyposis symptoms (nasal blockage, nasal congestion, runny nose, postnasal drip (mucus drainage down the throat), headache, facial pain, facial pressure, and difficulty with sense of smell) and symptom impacts (difficulty with sleeping due to nasal symptoms and difficulty with daily activities due to nasal symptoms). Participants report the severity of each symptom and symptom impact at its worst using a 4-point verbal rating scale (0-None to 3-Severe).
Nasal Peak Inspiratory Flow [Baseline to Week 52]
Change from baseline in Nasal Peak Inspiratory Flow through Week 52. Nasal peak inspiratory flow evaluation represents a physiologic measure of the air flow through both nasal cavities during forced inspiration expressed in liters per minute.
Asthma Control in Participants with Comorbid Asthma and Aspirin Exacerbated Respiratory Disease (AERD)/Nonsteroidal Anti-Inflammatory Drug Exacerbated Respiratory Disease (NSAID-ERD) [Baseline to Week 52]
Change from baseline in Asthma Control Questionnaire-6 at Week 52. The Asthma Control Questionnaire is an assessment of asthma symptoms (nighttime waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and short acting beta-agonist use). Participants are asked to recall their level of asthma control during the previous week by responding to one bronchodilator use question and 5 symptom questions. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled).
Serum trough concentrations [Baseline to Week 52]
Serum trough concentrations at each scheduled visit.
Immunogenicity anti-drug antibodies [Baseline to Week 52]
Incidence of anti-drug antibodies (ADA) over 52 weeks.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants with physician-diagnosed CRSwNP for at least 12 months prior to Visit 1 that have:
Severity consistent with need for surgery as defined by total NPS ≥ 5 (≥ 2 for each nostril) at screening, as determined by the central reader
Nasal Congestion Score (NCS) ≥ 2 at Visit 1
Ongoing documented NP symptoms over > 8 weeks prior to screening such as rhinorrhea and/or reduction/loss of smell
SNOT-22 total score ≥ 30 at screening (Visit 1)
Any standard of care for treatment of CRSwNP provided the participant is stable on that treatment for 30 days prior to Visit 1
Documented treatment of nasal polyposis exacerbation with SCS for at least 3 consecutive days or one IM depo-injectable dose (or contraindications/intolerance to) within the past 12 months prior to Visit 1 but not within the last 3 months prior to Visit 1 and/or any history of NP surgery (or contraindications/intolerance to)

Exclusion Criteria:

Any clinically important comorbidities other than asthma (e.g. active lung infection, bronchiectasis, pulmonary fibrosis, cystic fibrosis, primary ciliary dyskinesia, allergic bronchopulmonary mycosis, hypereosinophilic syndromes, etc.) that could confound interpretation of clinical efficacy results.
Sinus surgery within 6 months of screening visit OR any sinus surgery in the past which changed the lateral wall of the nose making NPS evaluation impossible.
Positive COVID-19 PCR test (or COVID-19 rapid test) or COVID-19 entry screening questionnaire during the screening visit. In case of long turnaround time of the nasopharyngeal swab test results from central lab, the site has the following alternatives: Perform COVID-19 nasopharyngeal or oropharyngeal swab test through local lab, Perform a COVID-19 rapid antigen test at the site, provided it is approved by the local health authorities
Regular use of decongestants (topical or systematic) at enrolment is not allowed unless used for endoscopic procedure
Use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, mycophenolate, tacrolimus, gold, penicillamine, sulfasalazine, hydroxychloroquine, systemic corticosteroids or any experimental anti-inflammatory therapy) within 3 months prior to Visit 1 and during the study period. Systemic corticosteroid use is defined as treatment with a burst of systemic corticosteroids for at least 3 consecutive days or a single IM depo-injectable dose of corticosteroids (considered equivalent to a 3-day burst of systemic corticosteroids).
Receipt of COVID-19 vaccine (regardless of vaccine delivery platform) 28 days prior to date of IP administration at Visit 3 (randomisation visit).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35209
2	Research Site	Bakersfield	California	United States	93301
3	Research Site	Huntington Beach	California	United States	92647
4	Research Site	Los Angeles	California	United States	90073
5	Research Site	Newport Beach	California	United States	92663
6	Research Site	Riverside	California	United States	92506
7	Research Site	Roseville	California	United States	95661
8	Research Site	Walnut Creek	California	United States	94598
9	Research Site	Colorado Springs	Colorado	United States	80923
10	Research Site	Denver	Colorado	United States	80230
11	Research Site	Boca Raton	Florida	United States	33487
12	Research Site	Fort Lauderdale	Florida	United States	33301
13	Research Site	Atlanta	Georgia	United States	30308
14	Research Site	Chicago	Illinois	United States	60657
15	Research Site	Ames	Iowa	United States	50010
16	Research Site	Lakeside Park	Kentucky	United States	41017
17	Research Site	Louisville	Kentucky	United States	40205
18	Research Site	Baltimore	Maryland	United States	21224
19	Research Site	Boston	Massachusetts	United States	02115
20	Research Site	Boston	Massachusetts	United States	02115
21	Research Site	Columbia	Missouri	United States	65212
22	Research Site	New York	New York	United States	10003
23	Research Site	New York	New York	United States	10028
24	Research Site	Winston-Salem	North Carolina	United States	27103
25	Research Site	Oklahoma City	Oklahoma	United States	73120
26	Research Site	Conroe	Texas	United States	77304
27	Research Site	Dallas	Texas	United States	75231
28	Research Site	Norfolk	Virginia	United States	23507
29	Research Site	Spokane	Washington	United States	99201
30	Research Site	Hamilton	Ontario	Canada	L8S 1G5
31	Research Site	London	Ontario	Canada	N6A 4V2
32	Research Site	Montreal	Quebec	Canada	H2X 3E4
33	Research Site	Montreal	Quebec	Canada	H3G 1L5
34	Research Site	Montreal	Quebec	Canada	H4A 3J1
35	Research Site	Trois-Rivières	Quebec	Canada	G8T 7A1
36	Research Site	Quebec		Canada	G1S 4L8
37	Research Site	Quebec		Canada	G1V 4G5
38	Research Site	Quebec		Canada	G1V 4W2
39	Research Site	Bengbu		China	233060
40	Research Site	Chengdu		China	610072
41	Research Site	Fuzhou		China	350001
42	Research Site	Guangzhou		China	510120
43	Research Site	Hangzhou		China	310003
44	Research Site	Hangzhou		China	310014
45	Research Site	Hefei		China	230601
46	Research Site	Hengyang		China	50012
47	Research Site	Lanzhou		China	730030
48	Research Site	Nanchang		China	330006
49	Research Site	Nanjing		China	210009
50	Research Site	Qingdao		China	266011
51	Research Site	Shanghai		China	200003
52	Research Site	Shanghai		China	200031
53	Research Site	Shanghai		China	200065
54	Research Site	Shanghai		China	200433
55	Research Site	Shijiazhuang		China	050051
56	Research Site	Suzhou		China	215006
57	Research Site	Taizhou		China	225300
58	Research Site	Tianjin		China	300121
59	Research Site	Tianjin		China	300211
60	Research Site	Wenzhou		China	325027
61	Research Site	Wu Han		China	430060
62	Research Site	Xi'An		China
63	Research Site	Xicheng District		China	100050
64	Research Site	Yinchuan		China	750001
65	Research Site	Zhengzhou		China	450007
66	Research Site	Zunyi		China	563100
67	Research Site	Aarhus N		Denmark	8200
68	Research Site	Hillerød		Denmark	3400
69	Research Site	Hvidovre		Denmark	2650
70	Research Site	København NV		Denmark	2400
71	Research Site	Køge		Denmark	4600
72	Research Site	Odense		Denmark	5000
73	Research Site	Vejle		Denmark	7100
74	Research Site	Ålborg		Denmark	9000
75	Research Site	Berlin		Germany	10629
76	Research Site	Berlin		Germany	13353
77	Research Site	Dresden		Germany	01307
78	Research Site	Heidelberg		Germany	69120
79	Research Site	Lübeck		Germany	23538
80	Research Site	Marburg		Germany	35043
81	Research Site	München		Germany	81675
82	Research Site	Tübingen		Germany	72076
83	Research Site	Wiesbaden		Germany	65183
84	Research Site	Budapest		Hungary	1083
85	Research Site	Budapest		Hungary	1106
86	Research Site	Budapest		Hungary	1134
87	Research Site	Nyíregyháza		Hungary	4400
88	Research Site	Pécs		Hungary	7621
89	Research Site	Székesfehérvár		Hungary	8000
90	Research Site	Veszprém		Hungary	8200
91	Research Site	Holon		Israel	Israel
92	Research Site	Jerusalem		Israel	91120
93	Research Site	Kfar Saba		Israel	4428164
94	Research Site	Ramat Gan		Israel	52621
95	Research Site	Rehovot		Israel	7661041
96	Research Site	Tel Aviv		Israel	69710
97	Research Site	Bunkyo-ku		Japan	113-8431
98	Research Site	Chuo-shi		Japan	409-3898
99	Research Site	Habikino-shi		Japan	583-0886
100	Research Site	Ichikawa-shi		Japan	272-0111
101	Research Site	Itabashi-ku		Japan	173-8610
102	Research Site	Kashiwa-shi		Japan	277-0882
103	Research Site	Kisarazu-shi		Japan	292-8535
104	Research Site	Koshigaya-shi		Japan	343-0031
105	Research Site	Koshigaya-shi		Japan	343-8555
106	Research Site	Miyazaki-shi		Japan	880-8510
107	Research Site	Moriguchi-shi		Japan	570-0074
108	Research Site	Nagaoka-shi		Japan	940-8621
109	Research Site	Nerima-ku		Japan	177-0035
110	Research Site	Niigata-shi		Japan	951-8520
111	Research Site	Osaka-shi		Japan	553-0003
112	Research Site	Saitama-shi		Japan	336-8522
113	Research Site	Sapporo-shi		Japan	003-0022
114	Research Site	Sendai-shi		Japan	983-8512
115	Research Site	Suwa-shi		Japan	392-8510
116	Research Site	Toyama-shi		Japan	939-8282
117	Research Site	Toyonaka Shi		Japan	560-0082
118	Research Site	Yokohama-shi		Japan	227-8501
119	Research Site	Yokohama-shi		Japan	236-0037
120	Research Site	Yufu-shi		Japan	879-5593
121	Research Site	Kraków		Poland	31-513
122	Research Site	Nadarzyn		Poland	05-830
123	Research Site	Wrocław		Poland	50-556
124	Research Site	Wrocław		Poland	53-301
125	Research Site	Zawadzkie		Poland	47-120
126	Research Site	Łodź		Poland	90-153
127	Research Site	Barakaldo		Spain	48903
128	Research Site	Barcelona		Spain	08036
129	Research Site	Jerez de la Frontera		Spain	11407
130	Research Site	Madrid		Spain	28040
131	Research Site	Santiago de Compostela		Spain	15706
132	Research Site	Sevilla		Spain	41009
133	Research Site	Dundee		United Kingdom	DD1 9SY
134	Research Site	London		United Kingdom	SE1 9RT
135	Research Site	Manchester		United Kingdom	M13 9WL