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Trial record 1 of 1 for:    NOTUS | COPD
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Pivotal Study to Assess the Efficacy, Safety and Tolerability of Dupilumab in Patients With Moderate to Severe COPD With Type 2 Inflammation (NOTUS)

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ClinicalTrials.gov Identifier: NCT04456673
Recruitment Status : Recruiting
First Posted : July 2, 2020
Last Update Posted : December 21, 2022
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Study Description
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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)

Condition or disease Intervention/treatment Phase
Chronic Obstructive Pulmonary Disease Drug: Dupilumab SAR231893 Drug: Inhaled Corticosteroid Drug: Inhaled Long-Acting Beta Agonist Drug: Inhaled Long-Acting Muscarinic Antagonist Drug: Placebo Phase 3

Detailed Description:
Approximately 68 weeks including a 4-week screening period, a 52-week treatment period, and 12 weeks of follow-up
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 924 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : June 12, 2020
Estimated Primary Completion Date : July 1, 2023
Estimated Study Completion Date : October 20, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: COPD Lung Diseases
Drug Information available for: Dupilumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Dupilumab
Dupilumab administered every 2 weeks
 Drug: Dupilumab SAR231893

Pharmaceutical form: Solution for injection

Route of administration: Subcutaneous

Other Name: Dupixent

Drug: Inhaled Corticosteroid

Pharmaceutical form: Inhaled Powder

Route of administration: Oral inhalation


Drug: Inhaled Long-Acting Beta Agonist

Pharmaceutical form: Inhaled Powder

Route of administration: Oral inhalation


Drug: Inhaled Long-Acting Muscarinic Antagonist

Pharmaceutical form: Inhaled Powder

Route of administration: Oral inhalation
Placebo Comparator: Placebo
Placebo dose administered every 2 weeks
 Drug: Inhaled Corticosteroid

Pharmaceutical form: Inhaled Powder

Route of administration: Oral inhalation


Drug: Inhaled Long-Acting Beta Agonist

Pharmaceutical form: Inhaled Powder

Route of administration: Oral inhalation


Drug: Inhaled Long-Acting Muscarinic Antagonist

Pharmaceutical form: Inhaled Powder

Route of administration: Oral inhalation


Drug: Placebo

Pharmaceutical form: Solution for injection

Route of administration: Subcutaneous


Outcome Measures
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Primary Outcome Measures :
  1. Annual rate of acute COPD exacerbation (AECOPD) [ Time Frame: Baseline to week 52 ]
    Annualized rate of moderate or severe COPD exacerbations over the 52-week treatment period compared to placebo


Secondary Outcome Measures :
  1. Change in pre-bronchodilator FEV1 [ Time Frame: Baseline to week 12 ]
    Change in pre-bronchodilator FEV1 from baseline to Week 12 compared to placebo

  2. Change in SGRQ [ Time Frame: Baseline to week 52 ]
    Change from baseline to Week 52 in SGRQ total score compared to placebo

  3. Improvement in SGRQ [ Time Frame: Baseline to week 52 ]
    Proportion of patients with SGRQ improvement ≥4 points at Week 52

  4. Change in pre-bronchodilator FEV1 from baseline to Week 52 [ Time Frame: Baseline to week 52 ]
    Change in pre-bronchodilator FEV1 from baseline to Week 52 compared to placebo

  5. Change in pre-bronchodilator FEV1 from baseline to time points up to Week 44 [ Time Frame: Baseline to weeks 2, 4, 8, 24, 36, 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

  6. Change in post-bronchodilator FEV1 lung function [ Time Frame: Baseline to weeks 2, 4, 8, 12, 24, 36, 52 ]
    Change in post-bronchodilator FEV1 from baseline at Weeks 2, 4, 8, 12, 24, 36 and 52 compared to placebo

  7. Change in forced expiratory flow (FEF) 25-75% [ Time Frame: Baseline to weeks 2, 4, 8, 12, 24, 36, 44, 52 ]
    Change in FEF 25-75% from baseline to Weeks 2, 4, 8, 12, 24, 36, 44 and 52

  8. Annualized rate of severe AECOPD [ Time Frame: Baseline through week 52 ]
    Annualized rate of severe COPD exacerbations compared to placebo over the 52-week treatment period

  9. Time to first AECOPD [ Time Frame: Baseline through week 52 ]
    Time to first moderate or severe COPD exacerbation compared with placebo during the 52-week treatment period

  10. Adverse events [ Time Frame: Baseline through week 64 ]
    Number of adverse events (AEs)/treatment-emergent adverse events (TEAEs)

  11. Potentially clinically significant abnormality (PCSA) in laboratory tests [ Time Frame: Baseline through week 64 ]
    Percentage of patients with at least one incidence of PCSA

  12. Anti-drug antibodies [ Time Frame: Baseline through week 64 ]
    Incidence of anti-drug antibodies against dupilumab


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Exclusion Criteria:

Exclusion criteria:

  • COPD diagnosis for less than 12 months prior to randomization.
  • Participants with current diagnosis of asthma according to the Global Initiative for Asthma (GINA) guidelines, or documented history of asthma.
  • 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.
  • Long-term treatment with oxygen >4.0 L/min OR if a participant requires more than 2.0 L/min in order to maintain oxygen saturation >88%
  • 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 α-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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04456673


Contacts
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Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext option 6 Contact-US@sanofi.com

Locations
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Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
More Information
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Additional Information:

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT04456673    
Other Study ID Numbers: EFC15805
2018-001954-91 ( EudraCT Number )
U1111-1211-8837 ( Registry Identifier: ICTRP )
First Posted: July 2, 2020    Key Record Dates
Last Update Posted: December 21, 2022
Last Verified: December 20, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Inflammation
Pathologic Processes
Respiratory Tract Diseases
 Cholinergic Agents
Muscarinic Antagonists
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Cholinergic Antagonists