| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Idiopathic pulmonary fibrosis (IPF) |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10021240 |
| E.1.2 | Term | Idiopathic pulmonary fibrosis |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
• To determine the efficacy (as measured by pulmonary function) and safety of
CNTO 888 in subjects with IPF. |
|
| E.2.2 | Secondary objectives of the trial |
• To assess the effect of CNTO 888 on measures of disease progression.
• To assess the effect of CNTO 888 on patient reported outcomes, functional capacity measurements, and health-related quality of life in subjects with IPF.
• To assess the PK and PD of CNTO 888 in subjects with IPF. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.3 | Principal inclusion criteria |
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. See Attachment 3 for a suggested algorithm for the evaluation of a subject with suspected IPF. 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 before receiving any protocol
specific procedures.
11. Willing to adhere to the study visit schedule and other protocol requirements. |
|
| E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria may not be enrolled in the study:
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, denosine) 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-γ, 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 of recurrence for at least 3 months).
21. Have a transplanted organ (with the exception of a corneal transplant > 3 months prior to screening).
22. Known allergies or clinically significant reactions to murine, murine-human chimeric, or human proteins or other components of the product.
23. Significant bleeding diathesis or excessive risk of bleeding, including chronic
anticoagulant therapy. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint of this study is the rate of percent change (relative to baseline per 4-week interval) in FVC through Week 52. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 8 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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