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

17 Jun 2024 → ongoing

Decision date (initial)

2024-05-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Almirall S.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Pharmacokinetic, Efficacy, Safety

PART 1
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
PART 2
To assess the effectiveness of 36 weeks of lebrikizumab 500 mg Q12W and lebrikizumab 250 mg Q4W in improving disease severity, signs, and symptoms in adults and adolescents with moderate-to-severe AD who achieved a sustained clinical response.

Secondary objectives 1

1. PART 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 PART 2 To assess the impact of 36 weeks of lebrikizumab 500 mg Q12W and lebrikizumab 250 mg Q4W on patient-reported and Investigator-reported outcome measures in adults and adolescents with moderate-to-severe AD who achieved a sustained clinical response

Conditions and MedDRA coding

Atopic Dermatitis

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Participants eligible for inclusion in Part 1 of this trial must fulfil the following criteria: 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. Participants eligible for inclusion in Part 1 of this trial must fulfil the following criteria: 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).
3. Participants eligible for inclusion in Part 1 of this trial must fulfil the following criteria: Chronic AD (according to Hanifin and Rajka Criteria (Hanifin 1980)) that has been present for ≥1 year before the Screening visit.
4. Participants eligible for inclusion in Part 1 of this trial must fulfil the following criteria: EASI score ≥12 at the Day 1/Baseline Visit.
5. Participants eligible for inclusion in Part 1 of this trial must fulfil the following criteria: IGA score ≥3 (moderate) (scale of 0 [clear] to 4 [severe]) at the Baseline visit.
6. Participants eligible for inclusion in Part 1 of this trial must fulfil the following criteria: ≥10% BSA of AD involvement at the Day 1/Baseline visit.
7. Participants eligible for inclusion in Part 1 of this trial must fulfil the following criteria: History of inadequate response to treatment with topical medications; or determination that topical treatments are otherwise medically inadvisable.
8. Participants eligible for inclusion in Part 1 of this trial must fulfil the following criteria: Completed electronic diary (eDiary) entries for pruritus and sleep-loss for a minimum of 4 of 7 days before Day 1/Baseline.
9. Participants eligible for inclusion in Part 1 of this trial must fulfil the following criteria: Willing and able to comply with all clinic visits and study-related procedures and questionnaires.
10. Participants eligible for inclusion in Part 1 of this trial must fulfil the following criteria: For women of childbearing potential: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, double-barrier methods (eg, male condom used in combination with a cap, diaphragm or sponge with spermicide), or sexual abstinence.
11. In addition to the above requirements, participants eligible for inclusion in Part 2 of this trial must fulfil the following criterion: 11. Demonstrate clinical response to treatment at Week 24 of Part 1, defined as achieving EASI 75 or IGA 0/1 without the use of high-potency TCS within the prior 4 weeks or systemic corticosteroids at any time post baseline.
12. Note: Clinical response must be sustained at Baseline/Day 1 to qualify for randomisation in Part 2

Exclusion criteria 18

1. Prior treatment at any time with tralokinumab, lebrikizumab, or an oral JAK inhibitor.
2. History of human immunodeficiency virus (HIV) infection or known positive HIV serology.
3. 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.
4. Presence of skin comorbidities that may interfere with study assessments.
5. 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.
6. 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.
7. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study.
8. Any known hypersensitivity or allergic response to lebrikizumab or any component of the investigational medicinal product (IMP).
9. 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 (see Section 9.10.2).
10. History of anaphylaxis as defined by the Sampson criteria (Sampson 2006).
11. 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).
12. 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).
13. Known current or chronic infection with any hepatitis virus.
14. Known liver cirrhosis and/or chronic hepatitis of any aetiology.
15. Known active endoparasitic infection or at high risk of these infections.
16. 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.
17. For the scratch sensor substudy only: a history of allergic response to skin adhesives,active skin or systemic infection, aobstructive sleep, or restless leg syndrome, or currently taking prescription sleep medications. ctive AD on the back of the hand, or a preexisting sleep disorder, including insomnia,
18. For trial sites located in France only: refer to Appendix 1 for additional exclusion criteria.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PART 1 Percentage of participants achieving EASI score ≤7 at Week 24 PART 2 • Percentage of participants achieving EASI 75 at Week 36 • Percentage of participants with an IGA score of 0 or 1 and a reduction ≥2 points from baseline (Part 1) at Week 36

Secondary endpoints 21

1. PART 1: Time to EASI score ≤7
2. PART 1: Percentage of participants achieving EASI ≤5, and EASI ≤3 at Week 24
3. PART 1: Percentage of participants achieving EASI 75 and EASI 90 at Week 24
4. PART 1: Percentage of participants with an IGA score of 0 or 1 and a reduction ≥2 points at Week 24
5. PART 1: Percentage of participants achieving SCORAD 75 and SCORAD 90 at Week 24
6. PART 1: Percentage change in mTLSS (hands) from baseline at Week 24 , in participants with AD of the hands at baseline
7. PART 1: Pruritus: Percentage of participants with Pruritus NRS ≥4 at baseline achieving ≥4-point improvement in Pruritus NRS from baseline at Week 24
8. PART 1: Quality of Life: Percentage of participants achieving DLQI/cDLQI 0-1 at Week 24
9. PART 1: Quality of Life: Percentage of participants with DLQI ≥4 at baseline achieving ≥4 point improvement in DLQI from baseline at Week 24
10. PART 1: Quality of Life: Percentage of participants with cDLQI ≥6 at baseline achieving ≥6 point improvement in cDLQI from baseline at Week 24
11. PART 1: Sleep Loss Due to Itch: Percentage of participants with a Sleep-Loss Scale of ≥2 points at baseline achieving ≥2-point improvement at Week 24
12. PART 1: Disease Control: Percentage of participants with POEM ≥4 at baseline achieving ≥4 point improvement in POEM from baseline at Week 24
13. PART 2: Percentage of participants achieving EASI scores ≤7 and ≤3 at Week 36
14. PART 2: Percentage of participants achieving EASI 90 at Week 36
15. PART 2: Percentage of participants with pruritus NRS ≥4 at baseline (Part 1) achieving ≥4-point improvement in Pruritus NRS at Week 36
16. PART 2: Pruritus: Percentage of participants with pruritus NRS 0 or 1 at Week 36
17. PART 2: Quality of Life: Percentage of participants achieving DLQI/cDLQI 0 or 1 at Week 36
18. PART 2: Quality of Life: Percentage of participants with DLQI ≥4 at baseline (Part 1) achieving ≥4 point improvement in DLQI at Week 36
19. PART 2: Quality of Life: Percentage of participants with cDLQI ≥6 at baseline (Part 1) achieving ≥6 point improvement in cDLQI at Week 36
20. PART 2: Sleep Loss Due to Itch: Percentage of participants with a Sleep-Loss Scale of ≥2 points at baseline (Part 1) achieving ≥2-point improvement at Week 36
21. PART 2: Disease Control: Percentage of participants with POEM ≥4 at baseline (Part 1) achieving ≥4 point improvement in POEM at Week 36

Investigational products

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

Test 2

Placebo 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 8

Locations

6 EU/EEA countries · 94 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

Documents 106 files

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

Application history

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