Clinical trial NCT00786201: A Study to Evaluate the Safety and Effectiveness of CNTO 888 Administered Intravenously (IV) in Participants With Idiopathic Pulmonary Fibrosis (IPF)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Fibrosis
Keywords: CNTO 888
Idiopathic Pulmonary Fibrosis
IPF
Lead sponsor: Centocor, Inc.
Sponsor class: INDUSTRY
First posted: 2008-11-06
Enrollment: 126
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The experimental drug CNTO 888 is currently being studied in cancer patients with solid tumors and this study is the first to use this drug for patients with idiopathic pulmonary fibrosis (IPF). This study tests the safety and effectiveness of CNTO 888 compared to placebo. The purpose of this research study is to determine if CNTO 888 is safe and to determine its effects (good and bad) on patients with IPF. The study will be conducted at approximately 28 sites globally. Patients can remain on usual, accepted treatment for IPF while enrolled in the study. Participating in other experimental studies or taking other experimental medications while participating in this study will not be allowed.

Detailed description: This study tests the safety and effectiveness of an experimental drug, CNTO 888, compared to placebo. The purpose of this research study is to determine if CNTO 888 is safe and to determine its effects on patients with idiopathic pulmonary fibrosis (IPF). CNTO 888 has not been approved by any regulatory authority for use in patients with any condition. The screening phase of the study, where the study doctor will determine if a patient is eligible for the study will last for 1 to 4 weeks. The study will enroll and treat the first 20 patients as part of a safety evaluation, at selected sites. The patients will be randomized to placebo or 1 mg/kg or 5 mg/kg or 15 mg/kg CNTO 888. The study drug will be given through a needle inserted into the patient's vein (IV). A Data Monitoring Committee will be responsible to review this portion of the study, and the study in general. They will review all of the information from patients in this portion of the study, after patients have received three infusions of study agent, or 3 months have passed since the first patient was enrolled. After their review, they will recommend whether to continue enrolling additional patients for the remainder of the study, or require some modification to the study. Patients will receive study agent until Week 48 and will continue to be followed through Week 72 for assessment of safety and any other effects after discontinuation of therapy. Patients will be in the study for about 74 weeks. The end of the study is defined as the last visit of the last patient. Patients will be randomly assigned to 1 of 4 treatment groups. Group 1, placebo IV infusion administered over 90 minutes every 4 weeks, from Week 0 through Week 48. Group 2, CNTO 888 1 mg/kg IV infusion administered over 90 minutes every 4 weeks, from Week 0 through Week 48. Group 3, CNTO 888 5 mg/kg IV infusion administered over 90 minutes every 4 weeks, from Week 0 through Week 48. Group 4, CNTO 888 15 mg/kg IV infusion administered over 90 minutes every 4 weeks, from Week 0 through Week 48. Enrollment completed as planned. Dosing terminated after interim DMC (Data Monitoring Committee) review. Participants followed until trial completed.

Eligibility criteria: Inclusion Criteria:

* Forced Vital Capacity (FVC) \>= (greater than or equal to) 50% of the predicted value at screening
* Abnormal lung function test results that include evidence of restriction and impaired gas exchange, or evidence of desaturation at rest or exercise or decreased diffusing capacity of the lung for carbon monoxide (DLCO)
* Bibasilar reticular abnormalities with minimal ground-glass opacities on high-resolution computed tomography (HRCT) scans
* Have surgical lung biopsy evidence of usual interstitial pneumonia (UIP) and/or HRCT scan-based diagnosis of IPF
* Relative decrease of \>= 10% in forced vital capacity (FVC), or relative decrease of \>= 15% in DLCO, or evidence of clinically significant worsening on HRCT (eg, development of honeycombing, increase in opacities), or significant worsening of dyspnea at rest or with exertion.

Exclusion Criteria:

* Have evidence of interstitial pneumonia other than IPF
* Diagnosis of IPF is not confirmed by HRCT or lung biopsy results
* Partial pressure of oxygen in arterial blood (PaO2) \< 55 mmHg (sea level) or 50 mmHg (altitude) at rest on room air
* Have a diagnosis of other significant respiratory disorder (eg, asthma, tuberculosis (TB), sarcoidosis, aspergillosis, chronic obstructive pulmonary disease \[COPD\], or cystic fibrosis)
* Have obstruction on prebronchodilator pulmonary function tests (PFTs) (defined as FEV1/FVC \< 0.7) at screening or demonstrate an increase in FEV1 \>= 12% postbronchodilator.

Primary outcomes:
measure: Rate of Percent Change (Relative to Baseline per 4 Week Interval) in Forced Vital Capacity (FVC) Through Week 52
timeFrame: Baseline through Week 52
Secondary outcomes:
measure: Time to Disease Progression
timeFrame: Baseline through Week 52
measure: Absolute Change From Baseline in Forced Vital Capacity (FVC) at Week 52
timeFrame: Baseline through Week 52
measure: Relative Change From Baseline in Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) at Week 52
timeFrame: Baseline through Week 52
measure: Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 52
timeFrame: Baseline through Week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Miami
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Wichita
country: United States
state: Kansas
city: New Orleans
country: United States
state: Louisiana
city: Ann Arbor
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Cincinnati
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Spartanburg
country: United States
state: South Carolina
city: Nashville
country: United States
state: Tennessee
city: Salt Lake City
country: United States
state: Utah
city: Colchester
country: United States
state: Vermont
city: Leuven
country: Belgium
city: Edmonton
country: Canada
state: Alberta
city: Winnipeg
country: Canada
state: Manitoba
city: Halifax
country: Canada
state: Nova Scotia
city: Hamilton
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Vancouver
country: Canada
city: Bad Berka
country: Germany
city: Essen
country: Germany
city: Amsterdam
country: Netherlands
city: Nieuwegein
country: Netherlands
city: Rotterdam
country: Netherlands
city: Sittard
country: Netherlands
Study officials:
affiliation: Centocor, Inc.
name: Centocor, Inc. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Raghu G, Martinez FJ, Brown KK, Costabel U, Cottin V, Wells AU, Lancaster L, Gibson KF, Haddad T, Agarwal P, Mack M, Dasgupta B, Nnane IP, Flavin SK, Barnathan ES. CC-chemokine ligand 2 inhibition in idiopathic pulmonary fibrosis: a phase 2 trial of carlumab. Eur Respir J. 2015 Dec;46(6):1740-50. doi: 10.1183/13993003.01558-2014. Epub 2015 Oct 22.