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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04456673




Registration number
NCT04456673
Ethics application status
Date submitted
30/06/2020
Date registered
2/07/2020
Date last updated
8/04/2021

Titles & IDs
Public title
Pivotal Study to Assess the Efficacy, Safety and Tolerability of Dupilumab in Patients With Moderate to Severe COPD With Type 2 Inflammation
Scientific title
A Randomized, Double-blind, Placebo-controlled, Parallel-group, 52-week Pivotal Study to Assess the Efficacy, Safety, and Tolerability of Dupilumab in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD) With Type 2 Inflammation
Secondary ID [1] 0 0
2018-001954-91
Secondary ID [2] 0 0
EFC15805
Universal Trial Number (UTN)
Trial acronym
NOTUS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dupilumab SAR231893
Treatment: Drugs - Inhaled Corticosteroid
Treatment: Drugs - Inhaled Long-Acting Beta Agonist
Treatment: Drugs - Inhaled Long-Acting Muscarinic Antagonist
Treatment: Drugs - Placebo

Experimental: Dupilumab - Dupilmab administered every 2 weeks

Placebo Comparator: Placebo - Placebo dose administered every 2 weeks


Treatment: Drugs: Dupilumab SAR231893
Pharmaceutical form: Solution for injection
Route of administration: Subcutaneous

Treatment: Drugs: Inhaled Corticosteroid
Pharmaceutical form: Inhaled Powder
Route of administration: Oral inhalation

Treatment: Drugs: Inhaled Long-Acting Beta Agonist
Pharmaceutical form: Inhaled Powder
Route of administration: Oral inhalation

Treatment: Drugs: Inhaled Long-Acting Muscarinic Antagonist
Pharmaceutical form: Inhaled Powder
Route of administration: Oral inhalation

Treatment: Drugs: Placebo
Pharmaceutical form: Solution for injection
Route of administration: Subcutaneous

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annual rate of acute COPD exacerbation (AECOPD) - Annualized rate of moderate or severe COPD exacerbations over the 52-week treatment period compared to placebo
Timepoint [1] 0 0
Baseline to week 52
Secondary outcome [1] 0 0
Change in pre-bronchodilator FEV1 - Change in pre-bronchodilator FEV1 from baseline to Week 12 compared to placebo
Timepoint [1] 0 0
Baseline to week 12
Secondary outcome [2] 0 0
Change in SGRQ - Change from baseline to Week 52 in SGRQ total score compared to placebo
Timepoint [2] 0 0
Baseline to week 52
Secondary outcome [3] 0 0
Improvement in SGRQ - Proportion of patients with SGRQ improvement =4 points at Week 52
Timepoint [3] 0 0
Baseline to week 52
Secondary outcome [4] 0 0
Change in pre-bronchodilator FEV1 from baseline to Week 52 - Change in pre-bronchodilator FEV1 from baseline to Week 52 compared to placebo
Timepoint [4] 0 0
Baseline to week 52
Secondary outcome [5] 0 0
Change in pre-bronchodilator FEV1 from baseline to time points up to Week 44 - Change in pre-bronchodilator FEV1 from baseline to weeks other than 12 and 52 (i.e. Weeks 2, 4, 8, 24, 36, and 44) compared to placebo
Timepoint [5] 0 0
Baseline to weeks 2, 4, 8, 24, 36, 44
Secondary outcome [6] 0 0
Change in post-bronchodilator FEV1 lung function - Change in post-bronchodilator FEV1 from baseline at Weeks 2, 4, 8, 12, 24, 36 and 52 compared to placebo
Timepoint [6] 0 0
Baseline to weeks 2, 4, 8, 12, 24, 36, 52
Secondary outcome [7] 0 0
Change in forced expiratory flow (FEF) 25-75% - Change in FEF 25-75% from baseline to Weeks 2, 4, 8, 12, 24, 36, 44 and 52
Timepoint [7] 0 0
Baseline to weeks 2, 4, 8, 12, 24, 36, 44, 52
Secondary outcome [8] 0 0
Annualized rate of severe AECOPD - Annualized rate of severe COPD exacerbations compared to placebo over the 52-week treatment period
Timepoint [8] 0 0
Baseline through week 52
Secondary outcome [9] 0 0
Time to first AECOPD - Time to first moderate or severe COPD exacerbation compared with placebo during the 52-week treatment period
Timepoint [9] 0 0
Baseline through week 52
Secondary outcome [10] 0 0
Adverse events - Number of adverse events (AEs)/treatment-emergent adverse events (TEAEs)
Timepoint [10] 0 0
Baseline through week 64
Secondary outcome [11] 0 0
Potentially clinically significant abnormality (PCSA) in laboratory tests - Percentage of patients with at least one incidence of PCSA
Timepoint [11] 0 0
Baseline through week 64
Secondary outcome [12] 0 0
Anti-drug antibodies - Incidence of anti-drug antibodies against dupilumab
Timepoint [12] 0 0
Baseline through week 64

Eligibility
Key inclusion criteria
Inclusion criteria:

- Participants with a physician diagnosis of COPD who meet the following criteria at
screening:

- Current or former smokers with a smoking history of =10 pack-years.

- Moderate-to-severe COPD (post-bronchodilator FEV1/ forced vital capacity [FVC]
ratio <0.70 and post-bronchodilator FEV1 % predicted >30% and =70%).

- Medical Research Council (MRC) Dyspnea Scale grade =2.

- Patient-reported history of signs and symptoms of chronic bronchitis (chronic
productive cough) for 3 months in the year up to screening in the absence of
other known causes of chronic cough.

- Documented history of high exacerbation risk defined as exacerbation history of
=2 moderate or =1 severe within the year prior to inclusion. At least one
exacerbation should have occurred while the patient was taking inhaled
corticosteroid (ICS)/long acting beta agonist (LABA)/long acting muscarinic
antagonist (LAMA) (or LABA/LAMA if ICS is contraindicated). Moderate
exacerbations are recorded by the investigator and defined as AECOPD that require
either systemic corticosteroids (intramuscular, intravenous, or oral) and/or
antibiotics. One of the two required moderate exacerbations has to require the
use of systemic corticosteroids. Severe exacerbations are recorded by the
investigator and defined as AECOPD requiring hospitalization or observation > 24
hours in emergency department/urgent care facility.

- Background triple therapy (ICS + LABA + LAMA) for 3 months prior to randomization
with a stable dose of medication for =1 month prior to Visit 1; Double therapy
(LABA + LAMA) allowed if ICS is contraindicated.

- Evidence of Type 2 inflammation: Patients with blood eosinophils =300 cells/microliter
at Visit 1.
Minimum age
40 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- COPD diagnosis for less than 12 months prior to randomization.

- A current diagnosis of asthma or history of asthma according to the 2018 Global
Initiative for Asthma (GINA) guidelines or other accepted guidelines.

- Significant pulmonary disease other than COPD (e.g., lung fibrosis, sarcoidosis,
interstitial lung disease, pulmonary hypertension, bronchiectasis, Churg-Strauss
Syndrome etc) or another diagnosed pulmonary or systemic disease associated with
elevated peripheral eosinophil counts.

- Cor pulmonale, evidence of right cardiac failure.

- Treatment with oxygen of more than 12 hours per day.

- Hypercapnia requiring Bi-level ventilation.

- AECOPD as defined in inclusion criteria within 4 weeks prior to screening, or during
the screening period.

- Respiratory tract infection within 4 weeks prior to screening, or during the screening
period.

- History of, or planned pneumonectomy or lung volume reduction surgery. Patients who
are participating in the acute phase of a pulmonary rehabilitation program, ie, who
started rehabilitation <4 weeks prior to screening (Note: patients in the maintenance
phase of a rehabilitation program can be included).

- Diagnosis of a-1 anti-trypsin deficiency.

The above information is not intended to contain all considerations relevant to a patient's
potential participation in a clinical trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 0360001 - Murdoch
Recruitment hospital [2] 0 0
Investigational Site Number 0360003 - Westmead
Recruitment postcode(s) [1] 0 0
6150 - Murdoch
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment outside Australia
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Humenne
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Poprad
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Cape Town
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South Africa
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Durban
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South Africa
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Gatesville
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South Africa
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Parow
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South Africa
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Pretoria
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Valencia
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Ukraine
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Ivano-Frankivsk
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Kharkiv
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Ukraine
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Kyiv
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Lviv
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Ukraine
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Zaporizhzhia
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Ukraine
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Zaporizhzhya
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United Kingdom
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Blackpool
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United Kingdom
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Bradford
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United Kingdom
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Bristol
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United Kingdom
State/province [138] 0 0
North Shields
Country [139] 0 0
United Kingdom
State/province [139] 0 0
Swansea

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sanofi
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Regeneron Pharmaceuticals
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Primary Objective:

To evaluate the efficacy of dupilumab administered every 2 weeks in patients with moderate or
severe Chronic Obstructive Pulmonary Disease (COPD) as measured by

- Annualized rate of acute moderate or severe COPD exacerbation (AECOPD)

Secondary Objectives:

To evaluate the effect of dupilumab administered every 2 weeks on

- Pre-bronchodilator forced expiratory volume in 1 second (FEV1) over 12 weeks compared to
placebo

- Health related quality of life, assessed by the change from baseline to Week 52 in the
St. George's Respiratory Questionnaire (SGRQ)

- Pre-bronchodilator FEV1 over 52 weeks compared to placebo

- Lung function assessments

- Moderate and severe COPD exacerbations

- To evaluate safety and tolerability

- To evaluate dupilumab systemic exposure and incidence of antidrug antibodies (ADA)
Trial website
https://clinicaltrials.gov/show/NCT04456673
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Trial Transparency email recommended (Toll free number for US & Canada)
Address 0 0
Country 0 0
Phone 0 0
800-633-1610
Fax 0 0
Email 0 0
Contact-US@sanofi.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04456673