E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Atopic dermatitis (AD) or eczema is a common inflammatory skin disease characterized by dry skin, red and crusting rash and intense pruritus (itch) that may affect people of all ages. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003639 |
E.1.2 | Term | Atopic dermatitis |
E.1.2 | System Organ Class | 100000004858 |
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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 primary objective of this study is to evaluate the safety and efficacy of lebrikizumab compared with placebo in patients with moderate-to-severe atopic dermatitis. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female adults and adolescents (≥12 to <18 years of age and weighing ≥40 kg).
- Chronic AD (according to American Academy of Dermatology Consensus Criteria) that has been present for ≥1 year before the screening visit.
- Eczema Area and Severity Index (EASI) score ≥16 at the baseline visit.
- Investigator Global Assessment (IGA) score ≥3 (scale of 0 to 4) at the baseline visit.
- ≥10% body surface area (BSA) of AD involvement at the baseline visit.
- History of inadequate response to treatment with topical medications; or determination that topical treatments are otherwise medically inadvisable.
- For women of childbearing potential: agree to remain abstinent (refrain from heterosexual intercourse) or use a highly effective contraceptive method during the treatment period and for at least 18 weeks after the last dose of lebrikizumab or placebo.
Note: A woman of childbearing potential (WOCBP) is defined as a
postmenarcheal female, who has not reached a postmenopausal state (12 continuous months of amenorrhea with no identified cause other
than menopause) and has not undergone surgical sterilization (removal of ovaries and/or uterus).
Note: The following are highly effective contraceptive methods:
combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) associated with inhibition
of ovulation, progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner, or sexual abstinence. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
- Male patients must agree to use an effective barrier method of contraception during the study and for a minimum of 18 weeks following the last dose of study drug if sexually active with a female of child bearing potential
- Provide signed informed consent/assent.
Please see Protocol Section 4.1 for the full list of inclusion criteria. |
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E.4 | Principal exclusion criteria |
- Participation in a prior lebrikizumab clinical study.
- History of anaphylaxis as defined by the Sampson criteria.
- Treatment with topical corticosteroids, calcineurin inhibitors or phosphodiesterase-4 inhibitors such as crisaborole within 1 week prior to the baseline visit.
- Prior treatment with dupilumab or tralokinumab.
- Treatment with any of the following agents within 4 weeks prior to the baseline visit:
a. Immunosuppressive/immunomodulating drugs (e.g., systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-γ, Janus kinase inhibitors, azathioprine, methotrexate, etc.)
b. Phototherapy and photochemotherapy (PUVA) for AD.
- Treatment with the following prior to the baseline visit:
a. An investigational drug within 8 weeks or within 5 half-lives (if known), whichever is longer.
b. B Cell-depleting biologics, including to rituximab, within 6 months.
c. Other biologics within 5 half-lives (if known) or 16 weeks, whichever is longer.
- Use of prescription moisturizers within 7 days of the baseline visit.
- Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the screening visit.
- Treatment with a live (attenuated) vaccine within 12 weeks of the baseline visit or planned during the study.
- Uncontrolled chronic disease that might require bursts of oral corticosteroids, e.g., co-morbid severe uncontrolled asthma (defined by an ACQ-5 score ≥1.5 or a history of ≥ 2 asthma exacerbations within the last 12 months requiring systemic [oral and/or parenteral] corticosteroid treatment or hospitalization for > 24 hours).
- Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study.
Please see Protocol Section 4.2 for the full list of exclusion criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- The percentage of patients with an IGA score of 0 or 1 and a reduction ≥2 points from Baseline to Week 16.
- Percentage of patients achieving EASI-75 (≥75% reduction from Baseline in EASI score) at Week 16 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Percentage of patients achieving EASI-90 (≥90% reduction from Baseline in EASI score) at Week 16
- Percentage change in Pruritus Numerical Rating Scale (NRS) score from Baseline to Week 16
- Percentage of patients with a Pruritus NRS of ≥5-points at Baseline who achieve a ≥4-point reduction from Baseline to Week 16
- Percentage of patients with a Pruritus NRS of ≥4-points at Baseline who achieve a ≥4-point reduction from Baseline to Week 16
- Percentage change in EASI score from Baseline to Week 16
- Percentage of patients achieving EASI-90 at Week 4
- Change from baseline in DLQI at Week 16
- Percentage of patients achieving ≥4-point improvement in DLQI from baseline to Week 16
- Percentage change in Sleep-loss score from Baseline to Week 16
- Change from Baseline in Sleep-loss score at Week 16
- Percentage of patients with a Pruritus NRS of ≥5-points at Baseline who achieve a ≥4-point reduction from Baseline to Weeks 1, 2 and 4
- Percentage of patients with a Pruritus NRS of ≥4-points at Baseline who achieve a ≥4-point reduction from Baseline to Weeks 1, 2 and 4
Specific for Maintenance Period:
- Percentage of patients from those re-randomized having achieved EASI-75 at Week 16 who continue to exhibit EASI-75 at Week 52 (EASI-75 calculated relative to baseline EASI score)
- Percentage of patients from those re-randomized having achieved IGA 0 or 1 and a ≥2-point improvement from Baseline at Week 16 who continue to exhibit an IGA 0 or 1 and a ≥2-point improvement from Baseline at Week 52
- Percentage of patients from those with a Pruritus NRS of ≥4-points at baseline re-randomized having achieved ≥4-point reduction from baseline at Week 16 who continue to exhibit ≥4-point reduction from baseline at Week 52
- Percentage of patients from those with a Pruritus NRS of ≥5-points at baseline re-randomized having achieved ≥4-point reduction from baseline at Week 16 who continue to exhibit ≥4-point reduction from baseline at Week 52
- Percentage change in SCORAD (having achieved EASI-75 at Week 16) from baseline at Week 52
- Evaluate the pharmacokinetics of lebrikizumab.
• Average serum lebrikizumab concentration |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At predetermined time points as listed in the protocol. |
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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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.8.1.7.1 | Other trial design description |
Induction Period, Maintenance Period |
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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 | 6 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 37 |
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 |
Canada |
Korea, Republic of |
United States |
Estonia |
France |
Latvia |
Lithuania |
Poland |
Spain |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 28 |