Clinical Trials Register

Summary
EudraCT Number:	2020-003062-39
Sponsor's Protocol Code Number:	D5242C00001
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-11-03
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Denmark - DHMA

A.2

EudraCT number

2020-003062-39

A.3

Full title of the trial

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)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Efficacy and safety of tezepelumab in participants with Severe Chronic Rhinosinusitis with Nasal Polyposis

A.3.2

Name or abbreviated title of the trial where available

WAYPOINT

A.4.1

Sponsor's protocol code number

D5242C00001

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04851964

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AstraZeneca AB
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AstraZeeneca AB
B.4.2	Country	Sweden
B.4.1	Name of organisation providing support	Amgen
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca AB
B.5.2	Functional name of contact point	Information Center
B.5.3	Address:
B.5.3.1	Street Address	N/A
B.5.3.2	Town/ city	N/A
B.5.3.3	Post code	N/A
B.5.3.4	Country	United States
B.5.6	E-mail	information.center@astrazeneca.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Tezepelumab via APFS
D.3.2	Product code	MEDI9929 anti-TSLP mAb (AMG157)
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tezepelumab
D.3.9.1	CAS number	1572943-04-4
D.3.9.2	Current sponsor code	MEDI9929
D.3.9.3	Other descriptive name	AMG157
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	99 to 121
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	Monoclonal antibody

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Severe Chronic Rhinosinusitis with Nasal Polyposis

E.1.1.1

Medical condition in easily understood language

Nasal Polyposis

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10080060
E.1.2	Term	Chronic rhinosinusitis with nasal polyps
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the effect of tezepelumab on Nasal Polyp Score and Participant Reported Nasal Congestion

E.2.2

Secondary objectives of the trial

Key Secondary Objectives:

To evaluate the effect of tezepelumab on loss of smell, nasal polypquality
of life compared with placebo, NP surgery and/or receiving SCS
for NP, sinus opacification, NPSD total symptom score (TSS), and lung
function in participants with co-morbid asthma and aspirin exacerbated
respiratory disease (AERD) /nonsteroidal anti-inflammatory drug
exacerbated respiratory disease (NSAID-ERD).

Other Secondary Objectives:

To evaluate the effect of tezepelumab on NPS, participant reported NC, loss of smell, sinus opacification, systemic corticosteroid use, NPSD, NPIF, asthma control in participants with co-morbid asthma and AERD/NSAID-ERD, and to evaluate the PK and immunogenicity of tezepelumab.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Participants with physician-diagnosed CRSwNP for at least 12 months prior to Visit 1 that have:
a. Severity consistent with need for surgery as defined by total NPS ≥ 5 (≥ 2 for each nostril) at screening, as determined by the central reader
b. Nasal Congestion Score (NCS) ≥ 2 at Visit 1
c. Ongoing documented NP symptoms over > 8 weeks prior to screening such as rhinorrhea and/or reduction/loss of smell

2. SNOT-22 total score ≥ 30 at screening (Visit 1)

3. Any standard of care for treatment of CRSwNP provided the participant is stable on that treatment for 30 days prior to Visit 1

4. 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)

Additional criteria to be checked prior to randomisation (Visit 3)

1. Confirmed central reading total NPS ≥ 5 (≥ 2 for each nostril) at Visit 2

2. Bi-weekly mean NCS≥ 2 (baseline bi-weekly mean score collected from study Day -13 to study Day 0)

3. SNOT-22 score ≥ 30 at randomisation (Visit 3)

4. At least 8 days of evaluable daily diary data in the 14-day period prior to randomisation (baseline bi-weekly mean score collected from study Day – 13 to study Day 0)

5. Subjects must have demonstrated a minimum 70% compliance with diary completion during the screening and run-in periods from Visit 1 to Visit 3.

6. At least 70% compliance with the participant’s background INCS as captured in the eDiary during the screening and run-in periods from Visit 1 to Visit 3.

E.4

Principal exclusion criteria

1. 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.

2. 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.

3. Positive COVID-19 PCR test (or COVID-19 rapid test) or COVID-19 entry screening questionnaire during the screening visit. Evaluation will be based on local standard of care as determined by current local guidelines

4. Regular use of decongestants (topical or systemic) at enrolment is not allowed unless used for endoscopic procedure.

5. Use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, mycophenolate, tacrolimus, gold, penicillamine, sulfasalazine, hydroxychloroquine, systemic corticosteroids for condition 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)

6. Receipt of COVID-19 vaccine (regardless of vaccine delivery platform) 28 days prior to date of IP administration at V3 (randomisation visit).

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in total NPS evaluated by nasal endoscopy at Week 52 and Change from baseline in bi-weekly mean NC score (NCS) evaluated as part of the Nasal Polyposis Symptom Diary (NPSD) at Week 52.

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline to Week 52

E.5.2

Secondary end point(s)

Key Secondary Endpoints:

At Week 52, change from baseline in bi-weekly mean loss of smell
evaluated as part of the NPSD, change from baseline in SNOT-22 scores,
change from baseline in Lund Mackay score (LMK) evaluated by CT,
change from baseline in bi-weekly mean NPSD TSS, and change from
baseline in pre-BD FEV1.

Time to surgery decision and/or SCS for NP, time to NP surgery decision, and time to SCS for NP up to Week 52.

Other Secondary Endpoints:

Through Week 52, change from baseline over time in NPS evaluated by nasal endoscopy, change from baseline over time in bi-weekly mean NCS evaluated by NPSD, change from baseline by domain of NPSD, and change from baseline in NPIF.

At Week 52, proportion of participants with (i) ≥1 point reduction and (ii) ≥2 points reduction in NPS, change from baseline in loss of smell evaluated by UPSIT test, change from baseline in modified LMK score evaluated by CT, sinus severity score by quantitative CT assessment, and change from baseline in ACQ-6. Exposure of SCS over 52 Weeks.

PK: Serum Concentration and Immunogenicity: Anti-drug antibody (ADA)

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline to Week 52

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Canada

China

Japan

United Kingdom

United States

Denmark

Germany

Hungary

Poland

Spain

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS (Last Visit of Last Subject)

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

350

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

158

F.4.2.2

In the whole clinical trial

400

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-01-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-12-16

P. End of Trial
P.	End of Trial Status	Ongoing

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