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 when used in combination with TCS treatment compared with placebo, in patients with moderate-to-severe AD. |
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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 |
1. Adults and adolescents ≥12 to <18 years of age and weighing ≥40 kg.
2. Chronic AD (according to American Academy of Dermatology Consensus Criteria) that has been present for ≥1 year before the screening visit (see
Appendix 2).
3. Eczema Area and Severity Index (EASI) score ≥16 at the baseline visit.
4. Investigator Global Assessment (IGA) score ≥3 (scale of 0 to 4) at the baseline visit (see Section 8.2.1).
5. ≥10% body surface area (BSA) of AD involvement at the baseline visit.
6. History of inadequate response to treatment with topical medications.
7. Applied a stable dose of non-medicated topical moisturizer at least twice daily for ≥7 days prior to the baseline visit.
8. Completed electronic diary entries for pruritus and sleep-loss for a minimum of 4 of 7 days preceding randomization.
9. Willing and able to comply with all clinic visits and study-related procedures and questionnaires.
10. 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.
11. 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
12. Provided signed informed consent/assent as described in Section 10.15.
13. Adolescent patients or their parents/caregivers who are willing and able to administer the study drug after training on proper injection techniques as required by this addendum.
14. Provide signed informed consent/assent to this addendum as described in Section 2.6. |
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E.4 | Principal exclusion criteria |
1. Participation in a prior lebrikizumab clinical study.
2. History of anaphylaxis as defined by the Sampson criteria (Sampson 2006).
3. Treatment with topical corticosteroids, calcineurin inhibitors or Phosphodiesterase-4 inhibitors such as crisaborole within 1 week prior to the baseline visit.
4. 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.
5. 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. Dupilumab within 8 weeks.
c. B-cell-depleting biologics, including rituximab, within 6 months.
d. Other biologics within 5 half-lives (if known) or 16 weeks, whichever is longer.
6. Use of prescription moisturizers within 7 days of the baseline visit.
7. Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the screening visit.
8. Treatment with a live (attenuated) vaccine within 12 weeks of the baseline visit or planned during the study.
9. 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).
10. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the baseline visit, or superficial skin infections within 1 week before the baseline visit.
NOTE: patients may be rescreened after infection resolves.
11. Evidence of active acute or chronic hepatitis (as defined by the Department of Health & Human Services Centers for Disease Control and Prevention) or known liver cirrhosis.
12. Diagnosed active endoparasitic infections or at high risk of these infections.
13. Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g., tuberculosis [TB], histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, and aspergillosis) despite infection resolution: or unusually frequent, recurrent, or prolonged infections, per the Investigator’s judgment.
14. History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening.
15. In the Investigator’s opinion, any clinically significant laboratory results from the chemistry, hematology or urinalysis tests obtained at the screening visit.
16. Presence of skin comorbidities that may interfere with study assessments.
17. History of malignancy, including mycosis fungoides, within 5 years before the screening visit, except completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin.
18. Severe concomitant illness(es) that in the Investigator’s judgment would adversely affect the patient’s participation in the study. Any other medical or psychological condition that in the opinion of the Investigator may suggest a new and/or insufficiently understood disease, may present an unreasonable risk to the study patient because of his/her participation in this clinical trial, may make patient’s participation unreliable, or may interfere with study assessments.
19. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study.
20. Have had an important side effect to TCS (e.g., intolerance to treatment, hypersensitivity reactions, significant skin atrophy, and systemic effects), as assessed by the investigator or treating physician that would prevent further use. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Co-primary endpoints will be used as follows:
• 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 ≥4-points at Baseline who achieve a ≥4-point reduction 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 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
• Proportion of TCS / TCI-free days from Baseline to Week 16
• Time (days) to TCS / TCI-free use 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 Weeks 1, 2 and 4
• 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
Other secondary endpoints:
• Proportion of patients with EASI-75, EASI-90 and EASI-50 by visit
• Proportion of patients with IGA Score of 0 or 1 and a reduction ≥2 points from Baseline by visit
• Percentage change from Baseline in EASI Score by visit
• Percentage change from Baseline in Pruritus NRS by visit
• Percentage of patients with Pruritus NRS change of ≥4 from Baseline by visit
• Percentage of patients with a Pruritus NRS score of ≥4 points at Baseline who achieve a ≥4-point reduction from Baseline by visit
• Change from Baseline in Sleep-Loss score by visit
• Change from Baseline in DLQI/CDLQI by visit
• Change from Baseline in EQ5D by visit
• Change from Baseline in POEM by visit
• Change from Baseline in PROMIS Anxiety measure by visit
• Change from Baseline in PROMIS Depression measure by visit
• Change in ACQ-5 score from Baseline to Week 16 in patients who have self-reported comorbid asthma
• Percentage change from Baseline to Week 16 in SCORAD
• The number and percentage of adolescent patients who respond "Strongly Agree" or "Agree" for each item of the modified SQAAQ on paper, for each of the 3 to 5 consecutive administration of the study drug |
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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 | No |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
Canada |
United States |
Germany |
Poland |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 7 |