Immunological Basis for Mepolizumab Activity in COPD

NCT05320939 | Unknown Phase 2 FDA Drug

• 1 other identifier: ISS Proposal # 12342
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

The current literature suggests that the mode of action of mepolizumab is to bind with Interleukin (IL)-5 and block the interaction of IL-5 with the IL-5Ra receptor on eosinophils. This removal of IL-5 may not explain all of the effects of mepolizumab. The investigators propose a set of studies to systematically examine the spectrum of effects of this drug on the immune system.

Conditions

COPD

Outcome Measures

Primary Outcomes (1)

• Change from baseline of peripheral blood eosinophil and B cell levels

  Peripheral blood eosinophil and B cell number counts

  6 months

Secondary Outcomes (8)

• Change from baseline of peripheral blood T cells

  6 months

• Change from baseline of peripheral blood monocytes

  6 months

• Change from baseline of peripheral blood neutrophils

  6 months

• Change from baseline of peripheral blood NK cells

  6 months

• Change from baseline of peripheral blood dendritic cells

  6 months

Study Arms (1)

Mepolizumab 100mg

EXPERIMENTAL

The Investigators will recruit a total of 30 subjects for this study (all subjects for the mepolizumab treatment).

Drug: Mepolizumab 100 MG

Interventions

Mepolizumab 100 MG DRUG

30 subjects (≥ 300 eosinophils/ul) will receive mepolizumab 100 mg subcutaneously every 4 weeks for 5 complete doses.

Mepolizumab 100mg

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Peripheral blood eosinophil count of ≥300 cells/μL from the hematology sample collected and a documented historical blood eosinophil count of ≥300/μL in the 12 months prior.
• Clinically documented history of Chronic Obstructive Pulmonary Disease (COPD) for at least 1 year in accordance with the definition by the American Thoracic Society/European Respiratory Society. A measured pre-and post-salbutamol FEV1/FVC ratio of \<0.70.
• Well-documented history (e.g., medical record verification) in the 12 months prior which includes 2 or more moderate COPD exacerbations that were treated with systemic corticosteroids (intramuscular (IM), intravenous, or oral) with or without antibiotics OR at least one severe COPD exacerbation requiring hospitalization.
• Current or former cigarette smokers with a history of cigarette smoking of ≥10 pack-years \[number of pack years = (number of cigarettes per day / 20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)\]. Former smokers are defined as those who have stopped smoking for at least 6 months prior.
• A female is eligible if the participant is not pregnant or breastfeeding, and at least one of the following conditions applies: 1) Is not a woman of childbearing potential (WOCBP) or 2) Is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of \<1% during the intervention period and for at least 16 weeks after the last dose of study intervention.
• A WOCBP must have a negative highly sensitive pregnancy urine test within 24 hours before the first dose of study intervention.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

You may not qualify if:

• Past history or concurrent diagnosis of asthma.
• An α1-antitrypsin deficiency as the underlying cause of COPD are excluded.
• Active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases.
• Pneumonia, COPD exacerbation, or lower respiratory tract infection within prior 4 weeks.
• Lung volume reduction surgery within the last 12 months.
• Participating in acute phase of a pulmonary rehabilitation program within last 4 weeks.
• Receiving treatment with oxygen more than 2 Liters(L)/minute at rest over 24 hours. If receiving oxygen treatment, an oxyhemoglobin saturation (as measured by PulseOx) greater than or equal to 89% while breathing supplemental oxygen.
• Myocardial infarction or unstable angina in the prior 6 months.
• Unstable or life threatening cardiac arrhythmia requiring intervention in the prior 3 months.
• New York Heart Association (NYHA) Class IV Heart failure.
• Historical or current evidence of clinically significant, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled.
• Other conditions that could lead to elevated eosinophils such as Hypereosinophilic syndromes including Eosinophilic Granulomatosis with Polyangiitis, or Eosinophilic Esophagitis.
• A known pre-existing parasitic infestation within prior 6 months.
• A current malignancy or previous history of cancer in remission for less than 12 months.
• A known immunodeficiency (e.g. human immunodeficiency virus - HIV), other than that explained by the use of corticosteroids taken for COPD.

Sponsors & Collaborators

• Temple University: lead
• GlaxoSmithKline: collaborator

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

mepolizumab

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Thomas Rogers, PhD

  Temple University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thomas Rogers, PhD

CONTACT

215-707-3215; rogerst@temple.edu

Lauren miller, BS/CRA

CONTACT

215-707-4821; lauren.e.miller@temple.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A pilot open-label single arm study.

Study Record Dates

• First Submitted: April 1, 2022
• First Posted: April 11, 2022
• Study Start: April 1, 2023
• Primary Completion: April 1, 2024
• Study Completion: May 1, 2025
• Last Updated: April 7, 2023

Record last verified: 2023-04