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AsthmaPhase 4NCT02654145

Omalizumab to Mepolizumab Switch Study in Severe Eosinophilic Asthma Patients

A Phase 4 study testing Mepolizumab 100mg SC, Albuterol/salbutamol MDIs and Omalizumab in people with Asthma, run by GlaxoSmithKline at 53 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Asthma
What is being tested?
Mepolizumab 100mg SC, Albuterol/salbutamol MDIs and Omalizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
145 participants
Where
53 sitesin 9 countries
Study dates
17 Mar 2016to 31 May 2017
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.]
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • Previous participation: Previously participated in any study with mepolizumab and received investigational product (including placebo).
  • Investigational Medications: Subjects who have received treatment with an investigational drug within the past 30 days or five terminal phase half-lives of the drug whichever is longer, prior to Screening (V1) (this also includes investigational formulations of marketed products).
  • Pregnancy: Subjects who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the time of study participation.

Trial locations and contacts

53 sites in 9 countries.

53 sites in 9 countries

United States13 sites
  • GSK Investigational Site

    Baltimore, Maryland, 21224

  • GSK Investigational Site

    Birmingham, Alabama, 35209

  • GSK Investigational Site

    Charlotte, North Carolina, 28277

  • GSK Investigational Site

    Durham, North Carolina, 27705

  • GSK Investigational Site

    East Providence, Rhode Island, 02914

  • GSK Investigational Site

    Piscataway, New Jersey, 08854

  • GSK Investigational Site

    Richmond, Virginia, 23229

  • GSK Investigational Site

    Riverside, California, 92506

  • GSK Investigational Site

    Rochester, New York, 14642

  • GSK Investigational Site

    Roseville, California, 95661

  • GSK Investigational Site

    San Diego, California, 92123

  • GSK Investigational Site

    Upland, California, 91786

  • GSK Investigational Site

    Williamsburg, Virginia, 23188

Other trials in United States

Canada9 sites
  • GSK Investigational Site

    Ajax, Ontario, L1S 2J5

  • GSK Investigational Site

    Calgary, Alberta, T2N 4Z6

  • GSK Investigational Site

    Mississauga, Ontario, L5A 3V4

  • GSK Investigational Site

    Montreal, Quebec, H3T1E2

  • GSK Investigational Site

    Sherwood Park, Alberta, T8H 0N2

  • GSK Investigational Site

    Toronto, Ontario, M4V 1R2

  • GSK Investigational Site

    Toronto, Ontario, M5T 3A9

  • GSK Investigational Site

    Vancouver, British Columbia, V5Z 1M9

  • GSK Investigational Site

    Windsor, Ontario, N8X 2G1

Other trials in Canada

France8 sites
  • GSK Investigational Site

    Bordeaux, 33076

  • GSK Investigational Site

    Grenoble, 38043

  • GSK Investigational Site

    Lyon, 69317

  • GSK Investigational Site

    Marseille, 13915

  • GSK Investigational Site

    Montpellier, 34295

  • GSK Investigational Site

    Nantes, 44093

  • GSK Investigational Site

    Paris, 75877

  • GSK Investigational Site

    Toulouse, 31059

Other trials in France

Spain7 sites
  • GSK Investigational Site

    Barcelona, 08035

  • GSK Investigational Site

    L'Hospitalet de Llobregat, 08907

  • GSK Investigational Site

    Laredo, Cantabria, 39770

  • GSK Investigational Site

    Murcia, 30003

  • GSK Investigational Site

    Pozuelo de Alarcón/Madrid, 28223

  • GSK Investigational Site

    Santiago de Compostela. La Coruña., 15706

  • GSK Investigational Site

    Valencia, 46017

Other trials in Spain

Argentina6 sites
  • GSK Investigational Site

    Buenos Aires, C1426ABP

  • GSK Investigational Site

    Florida, Buenos Aires, 1602

  • GSK Investigational Site

    La Plata, Buenos Aires, 1900

  • GSK Investigational Site

    Quilmes, Buenos Aires, B1878FNR

  • GSK Investigational Site

    Rosario, Santa Fe Province, 2000

  • GSK Investigational Site

    San Juan Bautista, Buenos Aires, 1888

Other trials in Argentina

Germany5 sites
  • GSK Investigational Site

    Berlin, 10717

  • GSK Investigational Site

    Berlin, 12203

  • GSK Investigational Site

    Hanover, Lower Saxony, 30173

  • GSK Investigational Site

    Leipzig, Saxony, 04357

  • GSK Investigational Site

    Neu-Isenburg, Hesse, 63263

Other trials in Germany

Netherlands2 sites
  • GSK Investigational Site

    Dordrecht, 3318 AT

  • GSK Investigational Site

    Rotterdam, 3045 PM

Other trials in Netherlands

Sweden2 sites
  • GSK Investigational Site

    Gothenburg, SE-413 45

  • GSK Investigational Site

    Stockholm, SE-141 86

Other trials in Sweden

Belgium1 site
  • GSK Investigational Site

    Erpent, 5101

Other trials in Belgium

About this study

Official title: A Multi-centre, Open Label, Single Arm, 32-week Treatment Study in Subjects With Severe Eosinophilic Asthma Not Optimally Controlled With Current Omalizumab Treatment Who Are Switched From Omalizumab to Mepolizumab 100mg Subcutaneous (Study Number 204471- the OSMO Study)

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
Being tested
Mepolizumab 100mg SC, Albuterol/salbutamol MDIs, Omalizumab
Keywords
mepolizumab, Omalizumab, SGRQ, severe eosinophilic asthma, ACQ, exacerbations
Medical subject headings
Asthma, Pulmonary Eosinophilia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Mepolizumab 100mg SCDrug

    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.

  • Albuterol/salbutamol MDIsDrug

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

  • OmalizumabDrug

    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.

Study groups in NCT02654145
Study groupRoleWhat they receive
Omalizumab switch to mepolizumab 100mg SC every 4 weeksExperimentalSubjects 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.
Receives: Drug: Mepolizumab 100mg SC; Drug: Albuterol/salbutamol MDIs; Drug: Omalizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline and at Week 32

Secondary outcomes (3)
  1. Mean Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Score at Week 32

    The SGRQ Questionnaire is a well-established, self-completed tool, comprising of 50 questions with 76 weighted responses designed to measure Quality of Life in participants with diseases of airway obstruction. It consists of two parts; Part 1 produces the symptom score and Part 2 produces the activity and impact score. A Total score is also calculated which summarizes the impact of the disease on overall health status. Scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and zero indicates best possible health status. 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 SGRQ 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 an ordinal variable) and visit.

    Measured: Baseline and at Week 32

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

    Clinically significant exacerbations of asthma were defined as worsening of asthma which requires use of systemic corticosteroids and/or hospitalization and/or Emergency Department (ED) visits. The frequency of clinically significant asthma exacerbations over 32 weeks' treatment was analyzed using Negative Binomial Regression via generalized estimating equations with a covariate of time period (pre-treatment versus on- and off treatment).

    Measured: Up to Week 32

  3. Ratio to Baseline in Blood Eosinophil Count at Week 32

    Blood samples were collected at specific time points to measure blood eosinophils level for evaluation of pharmacodynamic effects in participants with a severe eosinophilic asthma phenotype when they were directly switched to mepolizumab. Baseline was defined as the latest available assessment prior to first dose of mepolizumab and ratio to Baseline at Week 32 was defined as Week 32 value divided by Baseline value and was analyzed using Mixed Model Repeated Measures allowing for covariates of region, Baseline maintenance oral corticosteroid (OCS) therapy, exacerbations in the year prior to the study (as an ordinal variable) and visit. The log transformation was applied to blood eosinophil counts prior to analysis. If a blood eosinophil count of zero was reported, it was imputed with half of the lowest possible blood eosinophil count, where applicable, prior to log transforming the data. The dispersion measure used was log standard error.

    Measured: Baseline and at Week 32

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jan 2016 (estimated)
  2. Study start17 Mar 2016
  3. Primary completion31 May 2017
  4. Study completion31 May 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
145 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02654145
Sponsor's protocol ID
204471
Other IDs
2015-003697-32, 2015
Status last verified
Aug 2019
First submitted
11 Jan 2016
Last updated
19 Aug 2019
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Expanded access
Available

Publications

  • 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.

    PubMed 33971856

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Mepolizumab 100mg SC, Albuterol/salbutamol MDIs and Omalizumab in people with Asthma, run by GlaxoSmithKline at 53 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 53 sites in United States, Canada, France, Spain, Argentina and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Week 32 (time frame: Baseline and at Week 32). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02654145, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2019.

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