A Study to Evaluate the Safety and Effectiveness of CNTO 888 Administered Intravenously (IV) in Participants With Idiopathic Pulmonary Fibrosis (IPF)

Pulmonary Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00786201
• Other study ID #: CR015235
• Secondary ID: CNTO888PUL2001
• Status: Completed
• Phase: Phase 2
• First received: November 4, 2008
• Last updated: November 24, 2015
• Start date: December 2008
• Est. completion date: January 2012

Study information

• Verified date: November 2015
• Source: Centocor, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Ethics CommissionUnited States: Federal GovernmentUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 126
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Interstitial Pneumonias
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Drug:
• Placebo
Intravenous (IV) infusion every 4 weeks, from Week 0 through Week 48
• CNTO 888 1 mg/kg
IV infusion every 4 weeks, from Week 0 through Week 48
• CNTO 888 5 mg/kg
IV infusion every 4 weeks, from Week 0 through Week 48
• CNTO 888 15 mg/kg
IV infusion every 4 weeks, from Week 0 through Week 48

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Centocor, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Germany,  Netherlands, 

References & Publications (1)

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 carlu — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Percent Change (Relative to Baseline per 4 Week Interval) in Forced Vital Capacity (FVC) Through Week 52	The FVC is one component of pulmonary function testing, done with a spirometer.	Baseline through Week 52	No
Secondary	Time to Disease Progression	The time to disease progression is defined as the time in days from randomization to occurrence of acute idiopathic pulmonary fibrosis (IPF) exacerbation or lung transplantation or all-cause mortality, whichever occurs first.	Baseline through Week 52	No
Secondary	Absolute Change From Baseline in Forced Vital Capacity (FVC) at Week 52	The FVC is one component of pulmonary function testing, done with a spirometer.	Baseline through Week 52	No
Secondary	Relative Change From Baseline in Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) at Week 52	The DLCO is a sensitive lung function parameter and is performed to determine how well oxygen passes from the air sacs of the lungs into the blood.	Baseline through Week 52	No
Secondary	Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 52	The SGRQ is a 76-item questionnaire designed to measure the impact of respiratory disease and its treatment on the participants' health outcomes. The SGRQ is divided into 3 components: 1) symptoms, 2) activity limitations and 3) Impacts on social and psychological functioning.	Baseline through Week 52	No