A Phase 3b, Open-label Study to Evaluate the Effectiveness and Safety of Lebrikizumab Treatment in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Almirall S.A.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

24 Oct 2023 → 18 Jun 2025

Decision date (initial)

2023-10-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Almirall, S.A.

External identifiers

EU CT number

2023-505558-16-00

WHO UTN

U1111-1293-5750

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the effectiveness of 24 weeks of lebrikizumab in improving disease severity, signs, and symptoms in adults and adolescents with moderate-to-severe AD

Secondary objectives 1

1. To evaluate the impact of 24 weeks of lebrikizumab treatment on patient-reported and Investigator-reported outcome measures in adults and adolescents with moderate-to-severe AD

Conditions and MedDRA coding

Atopic Dermatitis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Adults and adolescents (aged ≥12 to <18 years at the time of informed consent form (ICF)/informed assent form (IAF) signature and weighing ≥40 kg) who are candidates for systemic AD therapy.
2. Chronic AD (according to Hanifin and Rajka Criteria) that has been present for ≥1 year before the Screening visit.
3. EASI score ≥12 at the Day 1/Baseline Visit.
4. IGA score ≥3 (moderate) (scale of 0 [clear] to 4 [severe]) at the Baseline visit.
5. ≥10% BSA of AD involvement at the Day 1/Baseline visit.
6. History of inadequate response to treatment with topical medications; or determination that topical treatments are otherwise medically inadvisable.
7. Completed electronic diary (eDiary) entries for pruritus and sleep-loss for a minimum of 4 of 7 days before Day 1/Baseline.
8. Willing and able to comply with all clinic visits and study-related procedures and questionnaires.
9. For women of childbearing potential: agree to remain abstinent (refrain from heterosexual intercourse) or to use a highly effective contraceptive method during the treatment period and for at least 4 weeks or 1 menstrual period after the last dose of lebrikizumab. NOTE: A woman of childbearing potential (WOCBP) is defined as a postmenarcheal woman, who has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause) and has not undergone surgical sterilisation (removal of ovaries and/or uterus). NOTE: The following contraceptive methods are highly effective: combined (oestrogen 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, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised 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 participant. Periodic abstinence (eg, calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception.
10. Participant must provide signed ICF. Adolescent participants must also provide separate informed assent to enrol in the study and sign and date either a separate IAF or the ICF signed by the parent/legal guardian (as appropriate based on local regulations and requirements).

Exclusion criteria 15

1. Prior treatment at any time with tralokinumab, lebrikizumab, or an oral JAK inhibitor.
2. Intention to use any concomitant medication or therapy that is not permitted by this protocol or failure to undergo the required washout period for a particular prohibited medication.
3. History of anaphylaxis as defined by the Sampson criteria.
4. Uncontrolled chronic disease that might require bursts of oral corticosteroids, eg, co-morbid severe uncontrolled asthma (defined by an Asthma Control Questionnaire-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 hospitalisation for >24 hours).
5. Occurrence of the following types of infection within 3 months before or during screening or development of these infections before Day 1 / Baseline: a. Serious (requiring hospitalisation, and/or IV or equivalent oral antibiotic treatment, as per the Investigator’s opinion); b. Opportunistic (as defined by Winthrop et al. (Winthrop 2015)) NOTE: Herpes zoster is considered active and ongoing until all vesicles are dry and crusted over; c. Chronic (duration of symptoms, signs, and/or treatment of 6 weeks or longer); d. Recurring (including, but not limited to herpes simplex, herpes zoster, recurring cellulitis, chronic osteomyelitis).
6. Known current or chronic infection with any hepatitis virus.
7. Known liver cirrhosis and/or chronic hepatitis of any aetiology.
8. Known active endoparasitic infection or at high risk of these infections.
9. Known or suspected history of immunosuppression, including history of invasive opportunistic infections (eg, tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, and aspergillosis) despite infection resolution: or unusually frequent, recurrent, or prolonged infections, per the Investigator’s judgement.
10. History of human immunodeficiency virus (HIV) infection or known positive HIV serology.
11. Any clinically significant laboratory test results from the chemistry or haematology tests obtained at the Screening visit that would jeopardise the patient’s participation in the study, per the Investigator’s judgement.
12. Presence of skin comorbidities that may interfere with study assessments.
13. 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 nonmetastatic squamous or basal cell carcinoma of the skin with no evidence of recurrence in the past 12 weeks.
14. Severe concomitant illness(es) that in the Investigator’s judgement would adversely affect the 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 participant because of his/her participation in this clinical trial, may make participation unreliable, or may interfere with study assessments.
15. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of participants achieving EASI score ≤7 at Week 24

Secondary endpoints 15

1. 1. Percentage of participants achieving EASI score ≤7, EASI ≤5, and EASI ≤3 by visit
2. 2. Percentage of participants achieving EASI 75, and EASI 90 by visit
3. 3. Percentage of participants with an IGA score of 0 or 1 and a reduction ≥2 points by visit
4. 4. Percentage of participants achieving SCORAD 75 and SCORAD 90 by visit
5. 5. Percentage change from baseline in mTLSS (hands) from baseline by visit
6. 6. Percentage of participants with a Face IGA score of 0 or 1 and a reduction ≥2 points by visit
7. 7. Percentage of participants with Pruritus NRS ≥4 at baseline achieving ≥4-point improvement in Pruritus NRS from baseline by visit
8. 8. Percentage of participants achieving DLQI 0-1 by visit
9. 9. Percentage of participants with DLQI ≥4 at baseline achieving ≥4-point improvement in DLQI from baseline by visit
10. 10. Percentage of participants achieving cDLQI 0-1 by visit
11. 11. Percentage of participants with cDLQI ≥6 at baseline achieving ≥6-point improvement in cDLQI from baseline by visit
12. 12. Percentage of participants with a Sleep-Loss Scale of ≥2 points at baseline who achieve at least 2-point reduction by visit
13. 13. Percentage of participants with POEM ≥4 at baseline achieving ≥4-point improvement in POEM from baseline by visit
14. 14. Itch Controlled Days questionnaire score by visit
15. 15. TSQM-9 by visit

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Almirall S.A.

Sponsor organisation

Almirall S.A.

Address

Ronda General Mitre 151

City

Barcelona

Postcode

08022

Country

Spain

Scientific contact point

Organisation

Almirall S.A.

Contact name

Aleksandra Stjepanovic

Public contact point

Organisation

Almirall S.A.

Contact name

Estrella Garcia

Third parties 5

Locations

2 EU/EEA countries · 33 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 35 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications