Proof-of-Concept Study to Assess the Efficacy, Safety and Tolerability of SAR440340 (Anti-IL-33 mAb) in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD)

Study Description

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Brief Summary:

Primary Objective:

To investigate effects of SAR440340 (anti-interleukin-33 [IL‑33] monoclonal antibody [mAb]) compared with placebo, on the annualized rate of moderate-to-severe acute exacerbations of COPD (AECOPD) over up to 52 weeks of treatment.

• Moderate exacerbations are recorded by the Investigator and defined as AECOPD that require either systemic corticosteroids (such as intramuscular, intravenous or oral) and/or antibiotics.
• Severe exacerbations are recorded by the Investigator and defined as AECOPD requiring hospitalization, emergency medical care visit or resulting in death.

Secondary Objectives:

To investigate effects of SAR440340 compared with placebo, on improving respiratory function, as assessed by pre‑bronchodilator forced exploratory volume in 1 second (FEV1).

To evaluate effects of SAR440340 compared with placebo, on Post-bronchodilator FEV1.

To evaluate effects of SAR440340 compared with placebo, on duration from baseline to first moderate or severe AECOPD event.

To evaluate effects of SAR440340 compared with placebo, on safety and tolerability.

Condition or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: SAR440340; Drug: Any Inhaled Corticosteroids as prescribed by treating physician as standard of care; Drug: Placebo; Drug: Any Long Acting Beta Agonist as prescribed by treating physician as standard of care; Drug: Any Long Acting Muscarinic Agonist as prescribed by treating physician as standard of care	Phase 2

Detailed Description:

Study participation for each patient will be up to a total of 46 weeks to 76 weeks including up to 10 days to 4 weeks of screening, 24 to 52 week treatment period on investigational medical product (IMP), and 20 weeks of post IMP treatment period.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	340 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, Proof-of-Concept (PoC) Study to Assess the Efficacy, Safety and Tolerability of SAR440340, in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD)
Actual Study Start Date :	July 16, 2018
Estimated Primary Completion Date :	April 23, 2020
Estimated Study Completion Date :	April 23, 2020

Arms and Interventions

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Arm	Intervention/treatment
Experimental: SAR440340; Administration of SAR440340 monotherapy injection	Drug: SAR440340; Pharmaceutical form: Solution for Injection Route of administration: Subcutaneous; Drug: Any Inhaled Corticosteroids as prescribed by treating physician as standard of care; Pharmaceutical form: Aerosol Route of administration: Inhaled; Drug: Any Long Acting Beta Agonist as prescribed by treating physician as standard of care; Pharmaceutical form: Aerosol Route of administration: Inhaled; Drug: Any Long Acting Muscarinic Agonist as prescribed by treating physician as standard of care; Pharmaceutical form: Aerosol Route of administration: Inhaled
Placebo Comparator: Placebo; Administration of matching placebo for injection of SAR440340	Drug: Any Inhaled Corticosteroids as prescribed by treating physician as standard of care; Pharmaceutical form: Aerosol Route of administration: Inhaled; Drug: Placebo; Pharmaceutical form: Solution for Injection Route of administration: Subcutaneous; Drug: Any Long Acting Beta Agonist as prescribed by treating physician as standard of care; Pharmaceutical form: Aerosol Route of administration: Inhaled; Drug: Any Long Acting Muscarinic Agonist as prescribed by treating physician as standard of care; Pharmaceutical form: Aerosol Route of administration: Inhaled

Outcome Measures

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Primary Outcome Measures :

1. Rate of moderate-to-severe acute Exacerbations in chronic obstructive pulmonary disease (AECOPD) patients [ Time Frame: Over up to 52 weeks treatment period ]
   Annualized rate of moderate-to-severe AECOPD over up to 52 weeks.

Secondary Outcome Measures :

1. Change in pre-bronchodilator forced expiratory volume in 1 second (FEV1) [ Time Frame: Baseline to Week 16-24 ]
   Change in pre-bronchodilator FEV1 from Week 16 to Week 24.
2. Time to first COPD Exacerbation [ Time Frame: Up to 52 weeks ]
   Time to first moderate or severe AECOPD.
3. Adverse Events [ Time Frame: Screening up to 72 weeks ]
   Monitor treatment emergent adverse events and serious adverse events.
4. Change in post-bronchodilator FEV1 [ Time Frame: Baseline to Week 24 ]
   Change from baseline to Week 24 in FEV1 (post-bronchodilator).

Eligibility Criteria

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Ages Eligible for Study:	40 Years to 75 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria :

• Participants with a diagnosis of Chronic Obstructive Pulmonary Disease (COPD) for at least 1 year (based on Global Initiative for Chronic Obstructive Lung Disease [GOLD] definition.
• Participants with moderate-to-severe COPD (post-bronchodilator Forced Expiratory Volume in 1 Second [FEV1]/forced vital capacity [FVC] <70% and post-bronchodilator FEV1 % predicted <80%, but ≥30%).
• Participants with COPD Assessment Test (CAT) score ≥10 at Screening Visit 1 and Visit 2/Randomization.
• Participants with reported history of signs and symptoms of chronic bronchitis (chronic productive cough for 3 months in the year up to screening in a patient in whom other causes of chronic cough [e.g., gastroesophageal reflux, chronic rhinosinusitis, bronchiectasis] have been excluded).
• Participants with a documented history (eg. medical record verification) of ≥2 moderate exacerbations or ≥1 severe exacerbation within the year prior to screening. A moderate exacerbation is defined as an acute exacerbation of COPD (AECOPD) requiring systemic corticosteroids (oral, intravenous, or intramuscular) and/or treatment with antibiotics (however, use of antibiotics alone does not qualify as a "moderate exacerbation" unless documentation is available that use of antibiotics was necessary for treatment of worsening symptoms of COPD). A severe exacerbation is defined as an AECOPD that required a hospitalization.

• Participants with Standard of Care background therapy, for 3 months prior to Visit 2/Randomization and at a stable dose for at least 1 month prior to the screening, including either:

  • Double therapy: Long acting beta agonist (LABA) + Long acting muscarinic agonist (LAMA) or inhaled corticosteroid (ICS) + LABA or ICS + LAMA or
  • Triple therapy: LABA + LAMA +ICS.
• Current or former smokers with a smoking history of ≥10 packs/year.

Exclusion criteria:

• Concomitant severe diseases or diseases for which the use of Inhaled Corticosteroids (ICS) (e.g., active pulmonary tuberculosis, etc.) or Long Acting Beta Agonists (LABA) are contraindicated (e.g., diagnosis of a history of significant cardiovascular diseases, insulin-dependent diabetes mellitus, hyperthyroidism, thyrotoxicosis, pheochromocytoma, hypokalemia).
• Participants with Bronchial thermoplasty procedure (up to 3 years prior to Visit 1)
• Participants with Chronic Obstructive Pulmonary Disease (COPD) diagnosed within the 6 months prior to randomization.
• A current diagnosis of asthma according to the Global Initiative for Asthma (GINA) guidelines.
• Significant pulmonary disease other than COPD (e.g., lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, bronchiectasis, eosinophilic granulomatosis with polyangiitis, significant sleep apnea on Bilevel Positive Airway Pressure, etc) or another diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts.
• Diagnosis of α-1 anti-trypsin deficiency.
• Advanced COPD with need for chronic (>15 hours/day) oxygen support.
• Participant with a moderate or severe Acute Exacerbation of COPD event within 4 weeks prior to screening.
• A participant who has experienced an upper or lower respiratory tract infection within 4 weeks prior to Screening/Visit 1 or during the screening period.
• Prior history of or planned pneumonectomy or lung volume reduction surgery.

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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Contacts

Contact: Trial Transparency email recommended (Toll free number for US & Canada)	800-633-1610 ext 1 then #	Contact-US@sanofi.com

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Sponsors and Collaborators

Sanofi

Regeneron Pharmaceuticals

Investigators

Study Director:	Clinical Sciences & Operations	Sanofi

More Information

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Responsible Party:	Sanofi
ClinicalTrials.gov Identifier:	NCT03546907 History of Changes
Other Study ID Numbers:	ACT15104; 2017-003290-34 ( EudraCT Number ); U1111-1194-2134 ( Other Identifier: UTN )
First Posted:	June 5, 2018
Last Update Posted:	January 14, 2019
Last Verified:	January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Muscarinic Agonists	Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs