A Phase 2, Multicenter, Multinational, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-ranging Study Evaluating the Efficacy and Safety of CNTO 888 Administered Intravenously in Subjects with Idiopathic Pulmonary Fibrosis
- Conditions
- Idiopathic Pulmonary Fibrosislungfibrosisusual interstitial pneumonia (UIP)10035597
- Registration Number
- NL-OMON37285
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 16
1. Aged 40 to 80, inclusive.
a. Subjects who are aged 40 years to < 50 years of age at the time of screening
will be required to have surgical lung biopsy evidence of UIP in order to be
considered eligible for the trial.
2. Physician diagnosis of IPF (according to a modified version of the ATS/ERS
criteria; ATS, 2000) within 4 years of screening.
Subjects must meet all of the major criteria and 3 of the 4 minor criteria listed
below:
Major criteria (must meet all)
a. Exclusion of other known causes of interstitial lung disease, such as certain
drug toxicities, environmental exposures, and connective tissue diseases.
b. Abnormal pulmonary function studies that include evidence of restriction
(reduced vital capacity, often with an increased FEV1/FVC ratio) and
impaired gas exchange (increased alveolar-arterial oxygen gradient
[P(A-a)O2] or evidence of desaturation at rest or exercise or decreased
DLCO).
c. Bibasilar reticular abnormalities with minimal ground-glass opacities on
HRCT scans.
Minor Criteria (must meet 3)
a. Age > 50 years.
b. Insidious onset of otherwise unexplained dyspnea on exertion.
c. Duration of illness * 3 months.
d. Bibasilar, inspiratory crackles (dry or *Velcro-type* in quality).
3. Have surgical lung biopsy evidence of UIP and/or HRCT scan-based diagnosis of
IPF. In the absence of surgical lung biopsy, an HRCT scan obtained within
3 months prior to or at screening must be available for review.
4. Have evidence of progressive IPF disease activity despite current treatment.
Progressive IPF disease activity, for the purposes of this protocol, is defined as
having 1 or more of the following within the past 12 months:
a. Relative decrease of * 10% in FVC.
b. Relative decrease of * 15% in DLCO.
c. Evidence of clinically significant worsening on HRCT (eg, development of
honeycombing, increase in opacities).
d. Significant worsening of dyspnea at rest or with exertion.
5. Evidence of recent stability of percent-predicted FVC (defined as not having
changed > 15% at the baseline visit relative to the screening visit).
6. FVC * 50% of the predicted value at screening.
7. Women of childbearing potential must have a negative serum pregnancy test result
at screening. Women of childbearing potential and all men must be using adequate
birth control measures and must agree to continue to use such measures and not become pregnant or plan a pregnancy until 12 months after receiving the last
infusion of study agent.
8. Are considered eligible according to the following TB screening criteria:
a. Have no history of latent or active TB prior to screening.
b. Have no signs or symptoms suggestive of active TB upon medical history
and/or physical examination.
c. Have had no recent close contact with a person with active TB.
d. Within 2 months prior to the first administration of study agent, have
negative diagnostic TB test results (defined as a negative QuantiFERON-TB
Gold test).
e. Have a chest radiograph (both posterior-anterior and lateral views) if
clinically indicated or HRCT taken within 3 months prior to screening and
read by a qualified radiologist, with no clear evidence of current active TB or
old inactive TB.
9. Capable of understanding subject assessment forms.
10. Have provided signed, written, informed consent
1. Have evidence of interstitial pneumonia other than IPF.
2. Diagnosis of IPF is not confirmed by HRCT or lung biopsy results.
3. Partial pressure of oxygen in arterial blood (PaO2) < 55 mmHg (sea level) or
50 mmHg (altitude) at rest on room air. If arterial blood gas results are not
available, an oxygen saturation via pulse oximetry (SpO2) < 88% with O2
supplementation at rest.
4. Known clinically significant pulmonary hypertension requiring vasodilator therapy
(eg, calcium channel blockers, prostacyclin or prostacyclin analogs, nitric oxide,
adenosine) or chronic anticoagulation therapy.
5. Have a diagnosis of other significant respiratory disorder (eg, asthma, TB,
sarcoidosis, aspergillosis, chronic obstructive pulmonary disease [COPD], or cystic
fibrosis).
6. Have obstruction on prebronchodilator PFTs (defined as FEV1/FVC < 0.7) at
screening.
7. Demonstrate an increase in FEV1 * 12% postbronchodilator.
8. Have a predicted life expectancy less than 1 year.
9. Previous treatment for IPF with an investigational/experimental medication within
6 weeks, or within 5 t1/2 of the investigational/experimental medication, whichever
is longer, prior to screening or are participating in another investigative study.
10. Current treatment with sildenafil, IFN-*, mycophenolate, or endothelin receptor
antagonists.
11. Current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic,
hematologic, gastrointestinal, endocrine, cardiac, neurologic, or cerebral disease, or
any laboratory abnormality which would pose/suggest a risk to the subject by
participation in the study.
12. Known to be seropositive for HIV, known active hepatitis A, B, or C infection, or
ALT/SGPT and/or AST/SGOT > 2 times the upper limit of normal at screening.
13. Within 3 months prior to screening, have had a clinically important, serious
infection (eg, hepatitis, pneumonia, or pyelonephritis), have been hospitalized for
an infection, or have been treated with IV antibiotics for an infection. Less serious
infections (eg, acute upper respiratory tract infection or simple urinary tract
infection) need not be considered exclusions at the discretion of the investigator.
14. Opportunistic infection (eg, cytomegalovirus, Pneumocystis carinii) within
6 months prior to screening.
15. Received any live attenuated vaccination (eg, FluMist) within 3 months prior to
screening or are expected to receive any live attenuated vaccinations during the trial
or up to 3 months after the last administration of study agent. Inactivated,
injectable influenza and pneumococcal vaccines are permissible.
16. Serious concomitant illness that could interfere with the subject*s participation in
the study.
17. History of substance abuse (drugs or alcohol) within the 3 years prior to screening, history of noncompliance to medical regimens, or other condition/circumstance that could interfere with the subject*s adherence to protocol requirements (eg,
psychiatric disease, lack of motivation, travel).
18. Major surgery within 1 month prior to screening or planned surgery during the
study.
19. Currently listed for lung transplantation.
20. Have any known malignancy or have a history of malignancy within the previous
5 years (with the exception of a nonmelanoma skin cancer that has been treated
with no evidence
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint of this study is the rate of percent change (relative to<br /><br>baseline per 4-week interval) in FVC through Week 52.</p><br>
- Secondary Outcome Measures
Name Time Method <p>The major secondary endpoints include:<br /><br>* Time to disease progression (defined as the time from randomization to<br /><br>occurrence of 1 of the<br /><br>following events, whichever occurs first: acute IPF exacerbation, lung<br /><br>transplantation, and/or all cause<br /><br>mortality) through Week 52.<br /><br>* Absolute change from baseline in FVC (mL) at Week 52.<br /><br>* Relative change from baseline in DLCO at Week 52.<br /><br>* Change from baseline in St. George*s Respiratory Questionnaire total score at<br /><br>Week 52.</p><br>