Pivotal Study to Assess the Efficacy, Safety and Tolerability of Dupilumab in Patients With Moderate to Severe COPD With Type 2 Inflammation

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

Sponsors

Lead Sponsor: Sanofi

Collaborator: Regeneron Pharmaceuticals

Source Sanofi
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)

Detailed Description

Approximately 68 weeks including a 4-week screening period, a 52-week treatment period, and 12 weeks of follow-up

Overall Status Recruiting
Start Date June 12, 2020
Completion Date June 2023
Primary Completion Date March 2023
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Annual rate of acute COPD exacerbation (AECOPD) Baseline to week 52
Secondary Outcome
Measure Time Frame
Change in pre-bronchodilator FEV1 Baseline to week 12
Change in SGRQ Baseline to week 52
Improvement in SGRQ Baseline to week 52
Change in pre-bronchodilator FEV1 from baseline to Week 52 Baseline to week 52
Change in pre-bronchodilator FEV1 from baseline to time points up to Week 48 Baseline to weeks 2, 4, 8, 16, 20, 24, 28, 36, 44, 48
Change in post-bronchodilator FEV1 lung function Baseline to weeks 2, 4, 8, 12, 24, 36, 52
Change in forced expiratory flow (FEF) 25-75% Baseline to weeks 2, 4, 8, 12, 16, 24, 28, 36, 44, 52
Annualized rate of severe AECOPD Baseline through week 52
Time to first AECOPD Baseline through week 52
Adverse events Baseline through week 64
Potentially clinically significant abnormality (PCSA) in laboratory tests Baseline through week 64
Anti-drug antibodies Baseline through week 64
Enrollment 924
Condition
Intervention

Intervention Type: Drug

Intervention Name: Dupilumab SAR231893

Description: Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

Arm Group Label: Dupilumab

Other Name: Dupixent

Intervention Type: Drug

Intervention Name: Inhaled Corticosteroid

Description: Pharmaceutical form: Inhaled Powder Route of administration: Oral inhalation

Intervention Type: Drug

Intervention Name: Inhaled Long-Acting Beta Agonist

Description: Pharmaceutical form: Inhaled Powder Route of administration: Oral inhalation

Intervention Type: Drug

Intervention Name: Inhaled Long-Acting Muscarinic Antagonist

Description: Pharmaceutical form: Inhaled Powder Route of administration: Oral inhalation

Intervention Type: Drug

Intervention Name: Placebo

Description: Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

Arm Group Label: Placebo

Eligibility

Criteria:

Inclusion criteria:

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

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

- Moderate-to-severe COPD (post-bronchodilator FEV1/ forced vital capacity [FVC] ≤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:

- 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 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.

Gender: All

Minimum Age: 40 Years

Maximum Age: 80 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Clinical Sciences & Operations Study Director Sanofi
Overall Contact

Last Name: Trial Transparency email recommended (Toll free number for US & Canada)

Phone: 800-633-1610

Phone Ext.: option 6

Email: [email protected]

Location
Facility: Status:
Investigational Site Number 8400031 | Bakersfield, California, 93301, United States Recruiting
Investigational Site Number 8400032 | Newport Beach, California, 92663, United States Recruiting
Investigational Site Number 8400015 | San Diego, California, 92120, United States Recruiting
Investigational Site Number 8400007 | Westminster, California, 92683, United States Recruiting
Investigational Site Number 8400018 | Lafayette, Colorado, 80026, United States Recruiting
Investigational Site Number 8400035 | Boynton Beach, Florida, 33435, United States Recruiting
Investigational Site Number 8400043 | Boynton Beach, Florida, 33437, United States Recruiting
Investigational Site Number 8400021 | DeBary, Florida, 32713, United States Recruiting
Investigational Site Number 8400039 | Fort Lauderdale, Florida, 33308, United States Recruiting
Investigational Site Number 8400012 | Miami, Florida, 33165, United States Recruiting
Investigational Site Number 8400013 | Saint Petersburg, Florida, 33704, United States Recruiting
Investigational Site Number 8400001 | Winter Park, Florida, 32789, United States Recruiting
Investigational Site Number 8400045 | Blue Ridge, Georgia, 30513, United States Recruiting
Investigational Site Number 8400003 | Rincon, Georgia, 31326, United States Recruiting
Investigational Site Number 8400034 | Rochester, Michigan, 48307, United States Recruiting
Investigational Site Number 8400017 | Chesterfield, Missouri, 63017-3625, United States Recruiting
Investigational Site Number 8400019 | Missoula, Montana, 59808, United States Recruiting
Investigational Site Number 8400016 | Lincoln, Nebraska, 68510, United States Recruiting
Investigational Site Number 8400044 | Westfield, New York, 14787, United States Recruiting
Investigational Site Number 8400010 | Gastonia, North Carolina, 28054, United States Recruiting
Investigational Site Number 8400006 | Mooresville, North Carolina, 28117, United States Recruiting
Investigational Site Number 8400025 | New Bern, North Carolina, 28562, United States Recruiting
Investigational Site Number 8400041 | Marion, Ohio, 43302, United States Recruiting
Investigational Site Number 8400024 | Toledo, Ohio, 43617, United States Recruiting
Investigational Site Number 8400009 | DuBois, Pennsylvania, 15801, United States Recruiting
Investigational Site Number 8400026 | Clinton, South Carolina, 29325, United States Recruiting
Investigational Site Number 8400002 | Spartanburg, South Carolina, 29303, United States Recruiting
Investigational Site Number 8400011 | Cypress, Texas, 77429, United States Recruiting
Investigational Site Number 8400029 | Lampasas, Texas, 76550-1820, United States Recruiting
Investigational Site Number 8400028 | Longview, Texas, 75605, United States Recruiting
Investigational Site Number 8400040 | Richmond, Virginia, 23236, United States Recruiting
Investigational Site Number 0320002 | Buenos Aires, C1121ABE, Argentina Recruiting
Investigational Site Number 0320006 | Caba, C1122AAK, Argentina Recruiting
Investigational Site Number 0320004 | Caba, C1414AIF, Argentina Recruiting
Investigational Site Number 0320001 | Caba, C1425BEN, Argentina Recruiting
Investigational Site Number 0320003 | Caba, C1425FVH, Argentina Recruiting
Investigational Site Number 0320005 | Quilmes, B1878FNR, Argentina Recruiting
Investigational Site Number 0320008 | Rosario, S2000DEJ, Argentina Recruiting
Investigational Site Number 0320009 | Rosario, S2002OJP, Argentina Recruiting
Investigational Site Number 0360001 | Murdoch, 6150, Australia Recruiting
Investigational Site Number 0360003 | Westmead, 2145, Australia Recruiting
Investigational Site Number 0560002 | Antwerpen, 2060, Belgium Recruiting
Investigational Site Number 0560001 | Leuven, 3000, Belgium Recruiting
Investigational Site Number 0560003 | Liege, 4000, Belgium Recruiting
Investigational Site Number 0560004 | Mechelen, 2800, Belgium Recruiting
Investigational Site Number 1005012 | Haskovo, 6305, Bulgaria Recruiting
Investigational Site Number 1005011 | Montana, 3400, Bulgaria Recruiting
Investigational Site Number 1005008 | Plovdiv, 4002, Bulgaria Recruiting
Investigational Site Number 1005013 | Ruse, 7002, Bulgaria Recruiting
Investigational Site Number 1005001 | Sofia, 1233, Bulgaria Recruiting
Investigational Site Number 1005002 | Sofia, 1407, Bulgaria Recruiting
Investigational Site Number 1005009 | Sofia, 1680, Bulgaria Recruiting
Investigational Site Number 1005004 | Stara Zagora, 6001, Bulgaria Recruiting
Investigational Site Number 1240010 | Ajax, L1S 2J5, Canada Recruiting
Investigational Site Number 1240008 | London, N5W 6A2, Canada Recruiting
Investigational Site Number 1240001 | Quebec, G1G 3Y8, Canada Recruiting
Investigational Site Number 1240005 | Quebec, G2J 0C4, Canada Recruiting
Investigational Site Number 1240009 | Sarnia, N7T 4X3, Canada Recruiting
Investigational Site Number 1240007 | Windsor, N8X 1T3, Canada Recruiting
Investigational Site Number 1520004 | Quillota, 2260877, Chile Recruiting
Investigational Site Number 1520007 | Santiago, 7500571, Chile Recruiting
Investigational Site Number 1520003 | Santiago, 7500692, Chile Recruiting
Investigational Site Number 1520002 | Santiago, 8910131, Chile Recruiting
Investigational Site Number 1520001 | Talca, Chile Recruiting
Investigational Site Number 1520011 | Temuco, 4781173, Chile Recruiting
Investigational Site Number 1520009 | Valdivia, 5110683, Chile Recruiting
Investigational Site Number 2760003 | Hannover, 30173, Germany Recruiting
Investigational Site Number 2760011 | Leipzig, 04357, Germany Recruiting
Investigational Site Number 2760010 | Lübeck, 23552, Germany Recruiting
Investigational Site Number 2760008 | Marburg, 35043, Germany Recruiting
Investigational Site Number 4280008 | Balvi, LV-4501, Latvia Recruiting
Investigational Site Number 4280007 | Rezekne, LV - 4601, Latvia Recruiting
Investigational Site Number 4280001 | Riga, LV -1010, Latvia Recruiting
Investigational Site Number 4280005 | Riga, LV -1010, Latvia Recruiting
Investigational Site Number 4280006 | Riga, LV -1021, Latvia Recruiting
Investigational Site Number 4280002 | Riga, LV-1002, Latvia Recruiting
Investigational Site Number 4280003 | Riga, LV-1038, Latvia Recruiting
Investigational Site Number 4400001 | Kaunas, 44320, Lithuania Recruiting
Investigational Site Number 4400003 | Kaunas, 49449, Lithuania Recruiting
Investigational Site Number 4400006 | Klaipeda, LT-92288, Lithuania Recruiting
Investigational Site Number 4400005 | Vilnius, 04130, Lithuania Recruiting
Investigational Site Number 5280005 | Arnhem, 6815 AD, Netherlands Recruiting
Investigational Site Number 6160008 | Bialystok, 15-044, Poland Recruiting
Investigational Site Number 6160014 | Elblag, 82-300, Poland Recruiting
Investigational Site Number 6160015 | Grodzisk Mazowiecki, 05-825, Poland Recruiting
Investigational Site Number 6160009 | Grudziadz, 86-300, Poland Recruiting
Investigational Site Number 6160011 | Katowice, 40-648, Poland Recruiting
Investigational Site Number 6160007 | Krakow, 31-559, Poland Recruiting
Investigational Site Number 6160010 | Rzeszow, 35-205, Poland Recruiting
Investigational Site Number 6200011 | Covilhã, 6200-251, Portugal Recruiting
Investigational Site Number 6200002 | Guimarães, 4810-061, Portugal Recruiting
Investigational Site Number 6430001 | Moscow, 115093, Russian Federation Recruiting
Investigational Site Number 6430003 | Moscow, 115280, Russian Federation Recruiting
Investigational Site Number 6430004 | St-Petersburg, 194354, Russian Federation Recruiting
Investigational Site Number 6430005 | Voronezh, 394066, Russian Federation Recruiting
Investigational Site Number 7100002 | Gatesville, 7764, South Africa Recruiting
Investigational Site Number 7240002 | Barcelona, 08023, Spain Recruiting
Investigational Site Number 8040002 | Ivano-Frankivsk, 76008, Ukraine Recruiting
Investigational Site Number 8040003 | Ivano-Frankivsk, 76018, Ukraine Recruiting
Investigational Site Number 8040001 | Kharkiv, 61124, Ukraine Recruiting
Investigational Site Number 8040007 | Kyiv, 01033, Ukraine Recruiting
Investigational Site Number 8040004 | Kyiv, 03049, Ukraine Recruiting
Investigational Site Number 8040006 | Lviv, 79011, Ukraine Recruiting
Investigational Site Number 8260002 | Blackpool, FY3 7DQ, United Kingdom Recruiting
Investigational Site Number 8260001 | Bradford, BD9 6RJ, United Kingdom Recruiting
Location Countries

Argentina

Australia

Belgium

Bulgaria

Canada

Chile

Germany

Latvia

Lithuania

Netherlands

Poland

Portugal

Russian Federation

South Africa

Spain

Ukraine

United Kingdom

United States

Verification Date

October 2020

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Dupilumab

Type: Experimental

Description: Dupilmab administered every 2 weeks

Label: Placebo

Type: Placebo Comparator

Description: Placebo dose administered every 2 weeks

Acronym NOTUS
Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

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

Source: ClinicalTrials.gov