E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Uncontrolled asthma despite the use of an inhaled corticosteroid
and a second controller medication. |
|
E.1.1.1 | Medical condition in easily understood language |
Uncontrolled asthma despite daily therapy. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
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 |
• The efficacy of lebrikizumab compared with placebo as measured by the rate of exacerbations
• The safety of lebrikizumab compared with placebo
• Periostin as a predictive biomarker (diagnostic)
• The efficacy and safety of different dose levels of lebrikizumab compared to placebo. |
|
E.2.2 | Secondary objectives of the trial |
The efficacy of lebrikizumab compared with placebo with respect to lung function, time to first exacerbation, fractional exhaled nitric oxide (FeNO), asthma-specific health-related quality of life, rescue medication use (i.e. short-acting β-agonists [SABA]), and health care utilization. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Ability and willingness to provide written informed consent and to comply with the study protocol
- 18–75 years old at screening
- Asthma diagnosis for ≥ 12 months prior to the start of screening
- Bronchodilator response (defined as a minimum 12% relative improvement in the volume of FEV1 after bronchodilator administration) during the screening period
- Pre-bronchodilator FEV1 40%–80% of predicted
- On ICS (500-2000 µg/day of fluticasone propionate DPI or equivalent, total daily dose) for ≥ 6 months prior to the start of screening
- On an eligible second controller medication for 6 months prior to the start of screening
- Uncontrolled asthma demonstrated during the screening period
- Chest X-ray or computed tomography (CT) scan obtained within 12 months prior to screening or chest X-ray during the screening period confirming the absence of other lung disease
- Demonstrated adherence with controller medication during the screening period.
|
|
E.4 | Principal exclusion criteria |
- History of a severe allergic reaction or anaphylactic reaction to a biologic agent
- Daily or alternate day oral corticosteroid maintenance therapy within the 3 months prior to screening
- Treatment with systemic corticosteroids within the 4 weeks prior to, or at anytime during the screening period
- Recent major episode of infection
- Active parasitic infection or Listeria monocytogenes infection within the 6 months prior to screening
- Active tuberculosis requiring treatment within the 12 months prior to screening
- Known immunodeficiency, including, but not limited to, HIV infection
- Evidence of acute or chronic hepatitis or known liver cirrhosis
- History of cystic fibrosis, chronic obstructive pulmonary disease, and/or other clinically significant lung disease other than asthma
- Known current malignancy or current evaluation for a potential malignancy
- Other clinically significant medical disease that is uncontrolled despite treatment or that is likely, in the opinion of the investigator, to require a change in therapy or impact the ability to participate in the study
- History of alcohol, drug, or chemical abuse
- Current smoker (cigarettes, pipe, cigar, or marijuana) or former smoker with a smoking history of > 10 pack-years
- Current use of an immunomodulatory/immunosuppressive therapy or past use within 3 months or 5 drug half-lives (whichever is longer) prior to screening
- Use of a biologic therapy including omalizumab (Xolair) at any time during the 6 months prior to screening
- Use of zileuton (ZYFLO) or roflumilast (Daxas, Daliresp) at any time during the 6 months prior to screening
- Treatment with an investigational agent within 30 days of screening (or 5 half lives of the investigational agent, whichever is longer)
- Receipt of a live/attenuated vaccine within the 4 weeks prior to sreening
- Female patients who are pregnant or lactating or unwilling to use a highly effective method of contraception
- Body mass index > 38 kg/m2
- Body weight < 40 kg. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Rate of asthma exacerbations. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Frequency of adverse events during the 52-week placebo-controlled period
• Severity of adverse events during the 52-week placebo-controlled period
• Incidence of anti-therapeutic antibodies during the study relative to the incidence at baseline
• Frequency and severity of adverse events during the 52-week active-treatment extension and during the 24-week safety follow-up period. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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.8.2.4 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 62 |
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 |
Argentina |
Australia |
Brazil |
Bulgaria |
Canada |
Chile |
China |
Colombia |
Czech Republic |
France |
Germany |
Hungary |
India |
Israel |
Italy |
Japan |
Korea, Republic of |
Mexico |
Peru |
Poland |
Russian Federation |
Slovakia |
South Africa |
Spain |
Turkey |
Ukraine |
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
|
The end of the study is defined as the date when the last patient, last visit (LPLV) occurs. The LPLV is expected to occur a maximum of 124 weeks after the last patient is enrolled and
randomized into the study. This timeframe includes the 52-week placebo-controlled period and a maximum of an additional 52-week active-treatment extension followed by the safety follow-up
period. All patients will be followed for safety for 24 weeks after the last dose of study treatment. |
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |