Effect of Anti-Inflammatory Agents on Biological Responses to Endotoxin Inhalation in Healthy Subjects

NCT02252809 | Completed Early Phase 1 DMC

• 1 other identifier: FXT-01
• Study Type: interventional
• Target: 51
• Locations: 0 countries
• Sites: N/A

Brief Summary

The main objective of this study is to characterize the biological responses elicited by endotoxin inhalation applied to healthy subjects, and to assess the effect of standard anti-inflammatory agents (i.e. adalimumab and methylprednisolone) on these biological responses.

Conditions

Innate Immunity

Keywords

inflammation endotoxin anti-TNF corticosteroids

Outcome Measures

Primary Outcomes (1)

• sputum cells count

  7 days

Study Arms (3)

adalimumab

ACTIVE COMPARATOR

adalimumab 40 mg by subcutaneous way 7 days before endotoxin inhalation

Drug: adalimumab

methylprednisolone

ACTIVE COMPARATOR

methylprednisolone 20 mg daily , 7 days before endotoxin inhalation

Drug: methylprednisolone

control

NO INTERVENTION

no intervention, 7 days before endotoxin inhalation

Interventions

adalimumab DRUG

adalimumab

methylprednisolone DRUG

methylprednisolone

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female aged 18 to 49 years, inclusive.
• Responsive to inhaled endotoxin; defined as a reduction of 10% or greater in forced expiratory volume in 1 second (FEV1) following inhalation of 20 µg equivalent of Clinical Center Reference Endotoxin.
• Have a body weight greater than 65 kg and a body mass index (BMI) below 30.
• Have normal lung function, defined as:
• Forced vital capacity (FVC) \> 80% of that predicted value;
• FEV1 \> 80% of that predicted value; and
• FEV1/FVC ratio \> 80% of predicted values.
• Have vital signs within the normal range, as follows:
• Oral body temperature: 35.0 to 36.5 °C.
• Blood pressure (BP):
• After at least 3 minutes of rest, measured in the supine position:
• Systolic BP: 90 to 140 mm Hg.
• Diastolic BP: 50 to 90 mm Hg.
• Then, after 1 minute standing:
• Systolic BP: no more than a 20 mmHg decrease.

You may not qualify if:

• Have any condition, including findings in the medical history or in the pre-study assessments, which, in the opinion of the investigator, constitute a risk or contraindication for the participation of the subject to the study, or that could interfere with the study objectives, conduct, or evaluation including, but not limited to:
• Any clinically significant abnormality in the results of pre-study safety laboratory tests.
• A positive test for drugs of abuse or alcohol breath test.
• Positive results from serum tests for Hepatitis B surface antigen (not due to vaccination), Hepatitis C, or Human Immunodeficiency Virus.
• History or presence of lung disease including asthma, chronic obstructive lung disease, or emphysema.
• History of atopy, including hay fever or atopic dermatitis.
• History or presence of liver disease.
• Hyperthyroidism, hypoglycemia, hyperglycemia, or diabetes mellitus.
• History or presence of autoimmune disorders including myositis, hepatitis, idiopathic thrombocytopenic purpura, psoriasis, rheumatoid arthritis, interstitial nephritis, Sjögren's syndrome, thyroiditis, or systemic lupus erythaematosus.
• Occurrence of any acute infection within the last 2 weeks before dosing.
• Presence or history of any severe allergic reactions; or history of allergy to any medications that may be used or prescribed in the course of this study (eg, albuterol, prednisolone, acetaminophen, aspirin or other non-steroidal anti-inflammatory agents, or adalimumab).
• History or presence of drug or alcohol abuse. (i;e. average daily intake of 3 units or a maximum weekly intake of greater than 21 units (1 unit equals 340 milliliters \[ml\] of beer, 115 ml of wine, or 43 ml of spirits).
• History or active manifestation of a serious psychiatric illness including depression, suicidal ideation, or psychosis.
• Positive test for latent tuberculosis.
• Loss or donation of blood within 12 weeks prior to entry into the study, or plasma donation within 1 week prior to entry into the study.

Sponsors & Collaborators

• Brugmann University Hospital: lead

Related Publications (1)

• Michel O, Dinh PH, Doyen V, Corazza F. Anti-TNF inhibits the airways neutrophilic inflammation induced by inhaled endotoxin in human. BMC Pharmacol Toxicol. 2014 Nov 3;15:60. doi: 10.1186/2050-6511-15-60.

  PMID: 25371053 DERIVED

MeSH Terms

Interventions

Adalimumab; Methylprednisolone

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Department

Study Record Dates

• First Submitted: September 23, 2014
• First Posted: September 30, 2014
• Study Start: November 1, 2008
• Primary Completion: April 1, 2009
• Study Completion: July 1, 2009
• Last Updated: September 30, 2014

Record last verified: 2014-09