Innate ImmunityEarly Phase 1NCT02252809
Effect of Anti-Inflammatory Agents on Biological Responses to Endotoxin Inhalation in Healthy Subjects
A Early Phase 1 study testing adalimumab and methylprednisolone in people with Innate Immunity, run by Brugmann University Hospital.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 49 yearsHealthy volunteers can take part
- Conditions the study is for
- Innate Immunity
- What is being tested?
- adalimumab and methylprednisolone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- No sites listed yet
- Study dates
- Nov 2008to Jul 2009
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 18 to 49 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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- 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.
- Diastolic BP: no more than a 10 mm Hg decrease.
- Heart rate: after at least 3 minutes of rest and measured in the supine position: 40 to 90 beats per minute (bpm).
- Have a hemoglobin level of 12.0 g/dL or more.
- Have been a non-smoker for the preceding 12 months.
- Willing and able to give written informed consent and to comply with the requirements of the study.
- Female subjects must not be pregnant or lactating.
- All subjects who are sexually active must use a medically acceptable and highly effective method of birth control for the duration of the study, and continue for 90 days after the end of treatment.
- -
Who cannot join
- 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.
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- 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.
- Use of any prescription drugs within 2 weeks or over-the-counter medication, including herbal supplements or multivitamins, within 1 week before drug administration without prior approval from the investigator.
- Use of any medication that may impact the results of any of the challenges, interfere with any other medications potentially used in the study, including steroids, beta blockers, or non-steroidal anti-inflammatory agents.
- Previous participation in this study, or administration of any investigational drug within 12 weeks prior to entry into the study.
- Exposure to endotoxin, within 12 weeks of signing the informed consent for this study.
- History of exposure to keyhole limpet hemocyanin (KLH), dog rabies vaccine, or history of immunization with inactivated Hepatitis A virus.
- -
About this study
Official title: An Open-Label, Parallel Group, Controlled Study in Healthy Subjects to Characterize Biological Responses to Immunological Challenges and to Measure the Effect of Marketed Anti-Inflammatory Agents on Those Responses
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.
Read the detailed description
This open-label, single-center, parallel-group clinical trial is designed to evaluate Humira® or methylprednisolone versus no treatment in healthy subjects applied inhaled endotoxin challenges.
A total of 30 healthy adult subjects who meet all inclusion and exclusion criteria will be randomised in a 1:1:1 ratio to one of the following cohorts:
- Cohort 1 subjects receive no study drug during the study.
- Cohort 2 subjects receive an oral 7-day course of the corticosteroid (methylprednisolone) during the study, starting on study Day 1. The daily dose is 20 mg.
- Cohort 3 subjects receive a single subcutaneous injection of the anti-tumor necrosis factor (TNF) (adalimumab) on study Day 1, administered as a 40 mg dose.
The study will include a Screening period of up to 21 days, during which subject eligibility will be assessed and Screening responses to endotoxin exposure challenge will be collected. Eligible subjects will initially undergo an 8-day treatment period, during which they will receive treatment based on their assigned cohort (or will receive no treatment if assigned to Cohort 1) and will be applied with the endotoxin challenges. After the treatment period, subjects will be followed up until study Day 42.
Efficacy evaluations will include specific responses to endotoxin challenge, and effects of methylprednisolone and adalimumab on these responses. Safety will be monitored throughout the study.
- Conditions
- Innate Immunity
- Being tested
- adalimumab, methylprednisolone
- Keywords
- inflammation endotoxin anti-TNF corticosteroids
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
adalimumabDrug
| Study group | Role | What they receive |
|---|---|---|
| adalimumab | Active comparator | adalimumab 40 mg by subcutaneous way 7 days before endotoxin inhalation Receives: Drug: adalimumab |
| methylprednisolone | Active comparator | methylprednisolone 20 mg daily , 7 days before endotoxin inhalation Receives: Drug: methylprednisolone |
| control | No intervention | no intervention, 7 days before endotoxin inhalation |
What is being measured
The primary outcome is the main question the study is designed to answer.
sputum cells count
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2014 (estimated)
- Study startNov 2008
- Primary completionApr 2009
- Study completionJul 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Innate ImmunityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brugmann University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Olivier Michel, Brugmann University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02252809
- Sponsor's protocol ID
- FXT-01
- Other IDs
- FXT-01
- Status last verified
- Sep 2014
- First submitted
- 23 Sep 2014
- Last updated
- 30 Sep 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 25371053
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Parallel Group, Controlled Study in Healthy Subjects to Characterize Biological Responses to Immunological Challenges and to Measure the Effect of Marketed Anti-Inflammatory Agents on Those Responses
- ClinicalTrials.gov ID
- NCT02252809
- Acronym / sponsor ID
- FXT-01
- Conditions
- Innate Immunity
- Keywords
- inflammation endotoxin anti-TNF corticosteroids
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Brugmann University HospitalUniversity, hospital or other
- Study start
- Nov 2008
- Primary completion
- Apr 2009 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 30 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This open-label, single-center, parallel-group clinical trial is designed to evaluate Humira® or methylprednisolone versus no treatment in healthy subjects applied inhaled endotoxin challenges.
A total of 30 healthy adult subjects who meet all inclusion and exclusion criteria will be randomised in a 1:1:1 ratio to one of the following cohorts:
- Cohort 1 subjects receive no study drug during the study.
- Cohort 2 subjects receive an oral 7-day course of the corticosteroid (methylprednisolone) during the study, starting on study Day 1. The daily dose is 20 mg.
- Cohort 3 subjects receive a single subcutaneous injection of the anti-tumor necrosis factor (TNF) (adalimumab) on study Day 1, administered as a 40 mg dose.
The study will include a Screening period of up to 21 days, during which subject eligibility will be assessed and Screening responses to endotoxin exposure challenge will be collected. Eligible subjects will initially undergo an 8-day treatment period, during which they will receive treatment based on their assigned cohort (or will receive no treatment if assigned to Cohort 1) and will be applied with the endotoxin challenges. After the treatment period, subjects will be followed up until study Day 42.
Efficacy evaluations will include specific responses to endotoxin challenge, and effects of methylprednisolone and adalimumab on these responses. Safety will be monitored throughout the study.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| adalimumab | Active comparator | Drug: adalimumabadalimumab 40 mg by subcutaneous way 7 days before endotoxin inhalation |
| methylprednisolone | Active comparator | Drug: methylprednisolonemethylprednisolone 20 mg daily , 7 days before endotoxin inhalation |
| control | No intervention | –no intervention, 7 days before endotoxin inhalation |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (23 listed)
- 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:
- Have vital signs within the normal range, as follows:
Key exclusion criteria (21 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| adalimumab | Drug | adalimumab |
| methylprednisolone | Drug | methylprednisolone |
Primary outcome
sputum cells count
Time frame: 7 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2014.
- Derived from this study: PubMed 25371053Michel 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing adalimumab and methylprednisolone in people with Innate Immunity, run by Brugmann University Hospital.
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 23 inclusion and 21 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 30 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
sputum cells count (time frame: 7 days). 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 NCT02252809, 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 30 Sep 2014.