Omalizumab to Mepolizumab Switch Study in Severe Eosinophilic Asthma Patients

NCT02654145 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: 2044712015-003697-32
• Study Type: interventional
• Target: 145
• Locations: 9 countries
• Sites: 53

Brief Summary

Mepolizumab is an anti-interleukin-5 ( IL-5) monoclonal antibody that neutralizes IL-5 and reduces eosinophil counts in both sputum and blood. Omalizumab an anti-immunoglobulin E (IgE) monoclonal antibody (mAb) is effective in the treatment of moderate to severe allergic asthma. The aim of this study is to investigate whether subjects not optimally controlled on their current omalizumab treatment, who are eligible for therapy with mepolizumab can be effectively and safely switched to treatment with mepolizumab to improve asthma control. The study will provide data on the efficacy, safety, immunogenicity, and tolerability of mepolizumab when switched directly from omalizumab without any wash-out. The learnings from this study may help guide physicians when substituting one biologic with another for the treatment of patients with severe eosinophilic asthma. The study will be a multi-centre, open-label single arm trial. Patients with severe eosinophilic asthma who are receiving omalizumab, but are not optimally controlled will be eligible to participate. Subjects will remain on their current maintenance therapy including omalizumab throughout the run-in period for a minimum of one week and up to 4 weeks. At Visit 2 (week 0) subjects will discontinue their omalizumab treatment and be switched to mepolizumab 100 mg subcutaneous (SC) every 4 weeks for 28 weeks. The treatment period is 32 weeks, including an Exit Visit/Early Withdrawal Visit, 4 weeks following the subject's last dose of mepolizumab.

Conditions

Asthma

Keywords

mepolizumab; Omalizumab; SGRQ; severe eosinophilic asthma; ACQ; exacerbations

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Week 32

  The ACQ-5 is a five-item, self-completed questionnaire, which is used as a measure of asthma control of a participant. The five questions (concerning nocturnal awakening, waking in the morning, activity limitation, shortness of breath and wheeze) enquire about the frequency and/or severity of symptoms over the previous week. The response options for all these questions range from zero (no impairment/limitation) to six (total impairment/ limitation) scale. ACQ-5 score range from 0 to 6. Higher scores indicates worsening of condition. Baseline was defined as the latest available assessment prior to first dose of mepolizumab. Change from Baseline at Week 32 was calculated as Week 32 value of ACQ-5 score minus Baseline value and was analyzed using Mixed Model Repeated Measures allowing for covariates of region, baseline maintenance OCS therapy, exacerbations in the year prior to the study (as ordinal variable) and visit.

  Baseline and at Week 32

Secondary Outcomes (3)

• Mean Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Score at Week 32

  Baseline and at Week 32

• The Rate of Clinically Significant Asthma Exacerbations Over 32 Weeks' Treatment

  Up to Week 32

• Ratio to Baseline in Blood Eosinophil Count at Week 32

  Baseline and at Week 32

Study Arms (1)

Omalizumab switch to mepolizumab 100mg SC every 4 weeks

EXPERIMENTAL

Subjects with severe eosinophilic asthma who are receiving omalizumab will enter a run-in period for a minimum of one week and a up to 4 weeks. Subjects will remain on their current maintenance therapy throughout the run-in period, including omalizumab. At Visit 2 (week 0) subjects will discontinue omalizumab treatment and will be switched to receiving mepolizumab 100 mg SC every 4 weeks for 28 weeks. Except for omalizumab, subjects will remain on their current maintenance therapy throughout the open-label treatment period. Albuterol/salbutamol metered dose inhalers (MDIs) will be provided as rescue medication during treatment period.

Drug: Mepolizumab 100mg SC; Drug: Albuterol/salbutamol MDIs; Drug: Omalizumab

Interventions

Mepolizumab 100mg SC DRUG

At Visit 2 (Week 0) eligible subjects will receive mepolizumab 100mg SC into the upper arm or thigh every 4 weeks over a period of 28 weeks.

Omalizumab switch to mepolizumab 100mg SC every 4 weeks

Albuterol/salbutamol MDIs DRUG

Albuterol/salbutamol metered dose inhalers (MDIs) will be provided as rescue medication during treatment period.

Omalizumab switch to mepolizumab 100mg SC every 4 weeks

Omalizumab DRUG

Subjects receiving omalizumab will enter in a run-in period and will continue to receive omalizumab throughout the run-in period. At Visit 2 (week 0) subjects will discontinue omalizumab.

Omalizumab switch to mepolizumab 100mg SC every 4 weeks

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 12 years of age at the time of signing the informed consent. For those countries where local regulations permit enrolment of adults only, subject recruitment will be restricted to those who are \>= 18 years of age.
• Asthma: A physician diagnosis of asthma for \>=2 years that meets the National Heart and Lung Institute guidelines.
• Forced expiratory volume in 1 second (FEV1): Persistent airflow obstruction as indicated by: For subjects \>=18 years of age at Visit 1, a pre-bronchodilator FEV1 \<80% predicted recorded at Visit 1, For subjects 12-17 years of age at Visit 1, a pre-bronchodilator FEV1 \<90% predicted recorded at Visit 1 or FEV1/ Forced Vital Capacity (FVC) ratio \<0.8 recorded at Visit 1
• Eosinophilic asthma: Airway inflammation characterized as eosinophilic in nature as indicated by one of the following: A peripheral blood eosinophil count of \>=300 cells/microliter (uL) that is related to asthma demonstrated in the past 12 months prior to Visit 1 or a peripheral blood eosinophil count of \>=150 cells/uL at Visit 1 that is related to asthma.
• Inhaled Corticosteroid: A well-documented requirement for regular treatment with high-dose inhaled corticosteroid (ICS) in the 12 months prior to Visit 1 with or without maintenance oral corticosteroids (OCS). For 18 years of age and older: ICS dose must be \>=880 microgram (ug)/day fluticasone propionate (FP) (ex-actuator) or equivalent daily. For ICS/ Long-Acting Beta-2-Agonists (LABA) combination preparations, the highest approved maintenance dose in the local country will meet this ICS criterion. For subjects 12-17 years of age at Visit 1: ICS dose must be \>=440 ug/day fluticasone propionate (FP) (ex-actuator) or equivalent daily, For ICS/LABA combination preparations, the highest approved maintenance dose in the local country will meet this ICS criterion.
• Controller Medication: Current treatment with an additional controller medication, besides ICS, for at least 3 months or a documented failure in the past 12 months of an additional controller medication for at least 3 successive months. \[e.g., LABA, leukotriene receptor antagonist (LTRA), or theophylline.\]
• Asthma symptoms not optimally controlled: An ACQ-5 score of \>=1.5 recorded at Visit 1.
• Omalizumab Treatment: Receiving omalizumab, based on weight and IgE levels, for at least the 4 months prior to Visit 1.
• Exacerbation history: Previously confirmed history of two or more exacerbations requiring treatment with systemic corticosteroids (intramuscular, intravenous, or oral) in the 12 months prior to Visit 1 despite the use of high-dose ICS. For subjects receiving omalizumab for \>=8 months, at least one exacerbation must have occurred while on omalizumab treatment. For subjects receiving maintenance oral corticosteroids, the corticosteroid treatment for the exacerbations must have been a two-fold dose increase or greater.
• Male or eligible Female: Females: a) Non-reproductive potential defined as :Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy, Postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels)\]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. b) Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication and until at least five terminal half-lives or until any continuing pharmacologic effect has ended, whichever is longer, after the last dose of study medication and completion of the Exit visit/Early Withdrawal visit.The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.

You may not qualify if:

• Concurrent Respiratory Disease: Presence of a known pre-existing, clinically important lung condition other than asthma. This includes current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer.
• Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to screening (subjects that had localized carcinoma of the skin which was resected for cure will not be excluded).
• Liver disease: Subjects must not be enrolled in the study if :At screening (Visit 1) Alanine Transaminase (ALT) \>2x Upper Limit of Normal (ULN); and bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%) Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment). Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice, or cirrhosis.
• Hepatitis status: Diagnosis of chronic hepatitis B, as evidenced by positive Hepatitis B surface antigen (HBsAg) at Visit 1. Chronic stable hepatitis C (e.g.,positive hepatitis C antibody test result at screening (Visit 1) or within 3 months prior to first dose of study treatment) are acceptable if subject otherwise meets entry criteria.
• Cardiovascular: Subjects who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment. Including but not limited to: a) known ejection fraction of \<30% or b) severe heart failure meeting New York Heart Association Class IV classification or c) hospitalised in the 12 months prior to Visit 1 for severe heart failure meeting New York Heart Association Class III or d) angina diagnosed less than 3 months prior to Visit 1 or at Visit 1
• Subjects with QT interval corrected (QTc) \> 450 milliseconds (msec) or QTc \> 480 msec in subjects with Bundle Branch Block at screening Visit 1.The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB), Fridericia's formula (QTcF), and/or another method, machine-read or manually over-read. The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial.For purposes of data analysis, QTcB, QTcF, another QT correction formula, or a composite of available values of QTc will be used.
• Other Concurrent Medical Conditions: Subjects who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological or any other system abnormalities that are uncontrolled with standard treatment.
• Eosinophilic Diseases: Subjects with other conditions that could lead to elevated eosinophils such as Hypereosinophilic Syndromes, including Churg-Strauss Syndrome (Eosinophilic Granulomatosis with Polyangiitis \[EGPA\]), or Eosinophilic Esophagitis. Subjects with a known, pre-existing parasitic infestation within 6 months prior to Visit 1 are also to be excluded.
• Immunodeficiency: A known immunodeficiency (e.g., human immunodeficiency virus \[HIV\]), other than that explained by the use of corticosteroids taken as therapy for asthma.
• Other Monoclonal Antibodies: Subjects who have received any monoclonal antibody (other than omalizumab) to treat inflammatory disease within 5 half-lives of Visit 1.
• Smoking history: Current smokers or former smokers with a smoking history of \>=10 pack years (number of pack years = (number of cigarettes per day / 20) x number of years smoked). A former smoker is defined as a subject who quit smoking at least 6 months prior to Screening Visit 1.
• Alcohol/Substance Abuse: A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.
• Adherence: Subjects who have known evidence of lack of adherence to controller medications and/or ability to follow physician's recommendations.
• Hypersensitivity: Subjects with allergy/intolerance to a monoclonal antibody or biologic. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
• Investigator opinion: Omalizumab treatment has provided significant clinical benefit despite experiencing 2 exacerbations in the past 12 months, and potential benefit from a switch to mepolizumab would not outweigh the potential harm after omalizumab withdrawal for the subject.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (53)

GSK Investigational Site

Birmingham, Alabama, 35209, United States

Location

GSK Investigational Site

Riverside, California, 92506, United States

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GSK Investigational Site

Roseville, California, 95661, United States

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GSK Investigational Site

San Diego, California, 92123, United States

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GSK Investigational Site

Upland, California, 91786, United States

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GSK Investigational Site

Baltimore, Maryland, 21224, United States

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GSK Investigational Site

Piscataway, New Jersey, 08854, United States

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GSK Investigational Site

Rochester, New York, 14642, United States

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GSK Investigational Site

Charlotte, North Carolina, 28277, United States

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GSK Investigational Site

Durham, North Carolina, 27705, United States

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GSK Investigational Site

East Providence, Rhode Island, 02914, United States

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GSK Investigational Site

Richmond, Virginia, 23229, United States

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GSK Investigational Site

Williamsburg, Virginia, 23188, United States

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GSK Investigational Site

Florida, Buenos Aires, 1602, Argentina

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GSK Investigational Site

La Plata, Buenos Aires, 1900, Argentina

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GSK Investigational Site

Quilmes, Buenos Aires, B1878FNR, Argentina

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GSK Investigational Site

San Juan Bautista, Buenos Aires, 1888, Argentina

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GSK Investigational Site

Rosario, Santa Fe Province, 2000, Argentina

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GSK Investigational Site

Buenos Aires, C1426ABP, Argentina

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GSK Investigational Site

Erpent, 5101, Belgium

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GSK Investigational Site

Calgary, Alberta, T2N 4Z6, Canada

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GSK Investigational Site

Sherwood Park, Alberta, T8H 0N2, Canada

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GSK Investigational Site

Vancouver, British Columbia, V5Z 1M9, Canada

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GSK Investigational Site

Ajax, Ontario, L1S 2J5, Canada

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GSK Investigational Site

Mississauga, Ontario, L5A 3V4, Canada

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GSK Investigational Site

Toronto, Ontario, M4V 1R2, Canada

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GSK Investigational Site

Toronto, Ontario, M5T 3A9, Canada

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GSK Investigational Site

Windsor, Ontario, N8X 2G1, Canada

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GSK Investigational Site

Montreal, Quebec, H3T1E2, Canada

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GSK Investigational Site

Bordeaux, 33076, France

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GSK Investigational Site

Grenoble, 38043, France

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GSK Investigational Site

Lyon, 69317, France

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GSK Investigational Site

Marseille, 13915, France

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GSK Investigational Site

Montpellier, 34295, France

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GSK Investigational Site

Nantes, 44093, France

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GSK Investigational Site

Paris, 75877, France

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GSK Investigational Site

Toulouse, 31059, France

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GSK Investigational Site

Neu-Isenburg, Hesse, 63263, Germany

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GSK Investigational Site

Hanover, Lower Saxony, 30173, Germany

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GSK Investigational Site

Leipzig, Saxony, 04357, Germany

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GSK Investigational Site

Berlin, 10717, Germany

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GSK Investigational Site

Berlin, 12203, Germany

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GSK Investigational Site

Dordrecht, 3318 AT, Netherlands

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GSK Investigational Site

Rotterdam, 3045 PM, Netherlands

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GSK Investigational Site

Laredo, Cantabria, 39770, Spain

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GSK Investigational Site

Barcelona, 08035, Spain

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GSK Investigational Site

L'Hospitalet de Llobregat, 08907, Spain

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GSK Investigational Site

Murcia, 30003, Spain

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GSK Investigational Site

Pozuelo de Alarcón/Madrid, 28223, Spain

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GSK Investigational Site

Santiago de Compostela. La Coruña., 15706, Spain

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GSK Investigational Site

Valencia, 46017, Spain

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GSK Investigational Site

Gothenburg, SE-413 45, Sweden

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GSK Investigational Site

Stockholm, SE-141 86, Sweden

Location

Related Publications (1)

• Liu MC, Chipps B, Munoz X, Devouassoux G, Bergna M, Smith SG, Price RG, Galkin DV, Azmi J, Mouneimne D, Albers FC, Chapman KR. Benefit of switching to mepolizumab from omalizumab in severe eosinophilic asthma based on patient characteristics. Respir Res. 2021 May 10;22(1):144. doi: 10.1186/s12931-021-01733-9.

  PMID: 33971856 DERIVED

MeSH Terms

Conditions

Asthma; Pulmonary Eosinophilia

Interventions

mepolizumab; Albuterol; Omalizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Antibodies, Anti-Idiotypic; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Serum Globulins; Globulins

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: January 11, 2016
• First Posted: January 13, 2016
• Study Start: March 17, 2016
• Primary Completion: May 31, 2017
• Study Completion: May 31, 2017
• Last Updated: August 19, 2019
• Results First Posted: January 31, 2018

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

FR (8); US (13); DE (5); ES (7); CA (9); AR (6); NL (2); BE (1); SE (2)