E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
IDIOPATHIC PULMONARY FIBROSIS |
|
E.1.1.1 | Medical condition in easily understood language |
IDIOPATHIC PULMONARY FIBROSIS |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•To evaluate lebrikizumab compared with placebo as monotherapy or as
combination therapy with pirfenidone background compared with
placebo in patients with IPF, as measured by the annualized rate of
decline in percent predicted forced vital capacity (FVC) over 52 weeks. |
|
E.2.2 | Secondary objectives of the trial |
•To evaluate lebrikizumab compared with placebo as monotherapy or as
combination therapy with pirfenidone background therapy compared
with placebo in patients with IPF as measured by:
oEfficacy on the basis of progression free survival (PFS), pulmonary
function, diffusion capacity, non elective hospitalization for any cause,
acute IPF exacerbation, proportion of patients with at least 10% decline
in percent predicted FVC or death, and all cause death
oThe distance walked in 6 minutes and health-related quality of life
questionnaires
•To evaluate the safety of lebrikizumab as monotherapy compared with placebo in patients with IPF
•To evaluate the safety of lebrikizumab with pirfenidone as background
therapy compared with placebo with pirfenidone as background therapy
in patients with IPF |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Adult patient, >/= 40 years of age
- Have a definite IPF diagnosis according to the 2011 ATS/ARS/ERS/ALAT consensus statement on IPF within the previous 5 years from time of screening and confirmed at baseline
- Forced vital capacity (FVC) >/= 40% and </=100% predicted at screening
- Stable baseline lung function as evidenced by a difference of < 10% in FVC (L) measurements between screening and Day 1, Visit 2 prior to randomization
- Diffusion capacity of the lung for carbon monoxide >/= 25% and </= 90% predicted at screening
- Ability to walk >/= 100 meters unassisted in 6 minutes.
- Cohort A (monotherapy): No background IPF therapy for >=4 weeks
allowed prior to randomization and throughout the placebo controlled
study period
- Cohort B (combination therapy): Tolerated dose of pirfenidone
<=2403 milligrams/once daily (mg/QD) for >=4 weeks required prior to
randomization and throughout the placebo controlled study period |
|
E.4 | Principal exclusion criteria |
- History of severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection
- Evidence of other known causes of interstitial lung disease (ILD)
- Lung transplant expected within 12 months of screening
- Evidence of clinically significant lung disease other than IPF
- Post bronchodilator forced expiratory volume in 1 second (FEV1)/FVC ratio < 0.7 at screening
- Positive bronchodilator response, evidenced by an increase of >/= 12% predicted and 200 mL increase in FEV1 or FVC
- Class IV New York Heart Association chronic heart failure or historical evidence of left ventricular ejection fraction < 35%
- Hospitalization due to an exacerbation of IPF within 4 weeks prior to or during screening
- Known current malignancy or current evaluation for potential malignancy
- An active upper or lower respiratory tract infection occurring at any
time within the screening period prior to the randomization visit
- Listeria monocytogenes infection or active parasitic infections within 6 months prior to Day 1, Visit 2
- Active tuberculosis requiring treatment within 12 months of screening
- Known immunodeficiency, including but not limited to HIV infection
- Past use of any anti-IL-13 or anti-IL-14/IL-13 therapy, including lebrikizumab
- Evidence of acute or chronic hepatitis or known liver cirrhosis.
Chronic treatment with pirfenidone within 4 weeks or five half lives
prior to screening (whichever is longer) to the end of the placebocontrolled
period (Day 365/Visit 16) (limited to Cohort A)
- For Cohort B: Known achalasia, esophageal stricture, or esophageal
dysfunction sufficient to limit the ability to swallow oral medication;
Tobacco smoking or use of tobacco-related products within 3 months of
screening or unwillingness to avoid smoking throughout the study; any
condition that, as assessed by the investigator, might be significantly
exacerbated by the known side effects associated with pirfenidone;
known or suspected peptic ulcer; use of strong CYP1A2 inhibitors (eg,
fluvoxamine or enoxacin) or moderate CYP1A2 inducers (limited to
tobacco smoking and tobacco related products) within 4 weeks of
randomization or during the study |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Annualized rate of decrease in percent predicted FVC over 52 weeks (% FVC/year) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Progression-free survival
2. Annualized rate of decrease in pulmonary function (FVC) over a 52
week period (mL/year)
3. Time from randomization to first occurrence of a of >= 10% absolute
decline in percent predicted FVC or death from any cause
4. Annualized rate of decrease in percent predicted in diffusion capacity
of the lung for carbon monoxide over 52 weeks
5. Annualized rate of decrease in ATAQ IPF total score over a 52 week
period
6. Time from randomization to non-elective hospitalization or death from
any cause
7. Annualized rate of decline in six minute walk test distance over 52
weeks
8. Time from randomization to first event of acute IPF exacerbation
9. Time from randomization to first occurrence of the St. George's
Respiratory Questionnaire (SGRQ) worsening
10. Safety: Incidence of adverse events |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-9. Up to Week 52
10. Up to 2.9 years |
|
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 | No |
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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
pirfenidone titration run-in period for cohort B/ combination therapy |
|
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.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
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 | No |
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 |
Australia |
Belgium |
Canada |
France |
Germany |
Italy |
Japan |
Mexico |
Peru |
Poland |
Spain |
United Kingdom |
United States |
|
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 | 4 |
E.8.9.1 | In the Member State concerned months | 9 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |