Lebrikizumab for Atopic dermatitis

Stratification factors

• Age group (adult vs. adolescent)
• EASI (≥12 to <16 vs. ≥16) at Baseline/Day 1 in Part 1
• P2 Baseline/Day 1 IGA (0 vs. ≥1)

Inclusion criteria

• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Note: Clinical response must be sustained at Baseline/Day 1 to qualify for randomisation in Part 2"}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Participants eligible for inclusion in Part 1 of this trial must fulfil the following criteria: EASI score ≥12 at the Day 1/Baseline Visit."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}

Exclusion criteria

• {"criterion_text":"- Prior treatment at any time with tralokinumab, lebrikizumab, or an oral JAK inhibitor."}
• {"criterion_text":"- History of human immunodeficiency virus (HIV) infection or known positive HIV serology."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Presence of skin comorbidities that may interfere with study assessments."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study."}
• {"criterion_text":"- Any known hypersensitivity or allergic response to lebrikizumab or any component of the investigational medicinal product (IMP)."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- History of anaphylaxis as defined by the Sampson criteria (Sampson 2006)."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Occurrence of the following types of infection within 3 months before or during screening or development of these infections before Day 1/Baseline: a.\tSerious (requiring hospitalisation, and/or IV or equivalent oral antibiotic treatment, as per the Investigator’s opinion); b.\tOpportunistic (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.\tChronic (duration of symptoms, signs, and/or treatment of 6 weeks or longer); d.\tRecurring (including, but not limited to herpes simplex, herpes zoster, recurring cellulitis, chronic osteomyelitis)."}
• {"criterion_text":"- Known current or chronic infection with any hepatitis virus."}
• {"criterion_text":"- Known liver cirrhosis and/or chronic hepatitis of any aetiology."}
• {"criterion_text":"- Known active endoparasitic infection or at high risk of these infections."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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,"}
• {"criterion_text":"- For trial sites located in France only: refer to Appendix 1 for additional exclusion criteria."}

Primary endpoints

• {"endpoint_text":"- PART 1 Percentage of participants achieving EASI score ≤7 at Week 24\n- PART 2 •\tPercentage of participants achieving EASI 75 at Week 36 •\tPercentage of participants with an IGA score of 0 or 1 and a reduction ≥2 points from baseline (Part 1) at Week 36","definition_or_measurement_approach":"Endpoints are measured using EASI (Eczema Area and Severity Index) and IGA (Investigator's Global Assessment) scales at specified timepoints (Week 24 for Part 1; Week 36 for Part 2)."}

Secondary endpoints

• {"endpoint_text":"- PART 1: Time to EASI score ≤7","definition_or_measurement_approach":"Time-to-event measured from baseline to first visit with EASI ≤7."}
• {"endpoint_text":"- PART 1: Percentage of participants achieving EASI ≤5, and EASI ≤3 at Week 24","definition_or_measurement_approach":"Proportion of participants reaching EASI thresholds at Week 24."}
• {"endpoint_text":"- PART 1: Percentage of participants achieving EASI 75 and EASI 90 at Week 24","definition_or_measurement_approach":"Proportion achieving ≥75% and ≥90% improvement in EASI from baseline at Week 24."}
• {"endpoint_text":"- PART 1: Percentage of participants with an IGA score of 0 or 1 and a reduction ≥2 points at Week 24","definition_or_measurement_approach":"Proportion with IGA 0/1 and ≥2-point reduction from baseline at Week 24."}
• {"endpoint_text":"- PART 1: Percentage of participants achieving SCORAD 75 and SCORAD 90 at Week 24","definition_or_measurement_approach":"Proportion achieving ≥75% and ≥90% improvement in SCORAD from baseline at Week 24."}
• {"endpoint_text":"- PART 1: Percentage change in mTLSS (hands) from baseline at Week 24 , in participants with AD of the hands at baseline","definition_or_measurement_approach":"Percent change in modified Total Lesion Severity Score for hands versus baseline at Week 24 among those with baseline hand involvement."}
• {"endpoint_text":"- PART 1: Pruritus: Percentage of participants with Pruritus NRS ≥4 at baseline achieving ≥4-point improvement in Pruritus NRS from baseline at Week 24","definition_or_measurement_approach":"Proportion of participants with baseline Pruritus NRS ≥4 achieving ≥4-point absolute improvement at Week 24."}
• {"endpoint_text":"- PART 1: Quality of Life: Percentage of participants achieving DLQI/cDLQI 0-1 at Week 24","definition_or_measurement_approach":"Proportion achieving DLQI or cDLQI score of 0 or 1 at Week 24."}
• {"endpoint_text":"- PART 1: Quality of Life: Percentage of participants with DLQI ≥4 at baseline achieving ≥4 point improvement in DLQI from baseline at Week 24","definition_or_measurement_approach":"Proportion with baseline DLQI ≥4 achieving ≥4-point improvement at Week 24."}
• {"endpoint_text":"- PART 1: Quality of Life: Percentage of participants with cDLQI ≥6 at baseline achieving ≥6 point improvement in cDLQI from baseline at Week 24","definition_or_measurement_approach":"Proportion with baseline cDLQI ≥6 achieving ≥6-point improvement at Week 24."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Proportion with baseline sleep-loss ≥2 achieving ≥2-point improvement at Week 24."}
• {"endpoint_text":"- PART 1: Disease Control: Percentage of participants with POEM ≥4 at baseline achieving ≥4 point improvement in POEM from baseline at Week 24","definition_or_measurement_approach":"Proportion with baseline POEM ≥4 achieving ≥4-point improvement at Week 24."}
• {"endpoint_text":"- PART 2: Percentage of participants achieving EASI scores ≤7 and ≤3 at Week 36","definition_or_measurement_approach":"Proportion achieving EASI thresholds at Week 36 (Part 2 randomized population)."}
• {"endpoint_text":"- PART 2: Percentage of participants achieving EASI 90 at Week 36","definition_or_measurement_approach":"Proportion achieving ≥90% improvement in EASI at Week 36."}
• {"endpoint_text":"- PART 2: Percentage of participants with pruritus NRS ≥4 at baseline (Part 1) achieving ≥4-point improvement in Pruritus NRS at Week 36","definition_or_measurement_approach":"Proportion with baseline pruritus NRS ≥4 achieving ≥4-point improvement at Week 36."}
• {"endpoint_text":"- PART 2: Pruritus: Percentage of participants with pruritus NRS 0 or 1 at Week 36","definition_or_measurement_approach":"Proportion with pruritus NRS of 0 or 1 at Week 36."}
• {"endpoint_text":"- PART 2: Quality of Life: Percentage of participants achieving DLQI/cDLQI 0 or 1 at Week 36","definition_or_measurement_approach":"Proportion achieving DLQI/cDLQI 0-1 at Week 36."}
• {"endpoint_text":"- PART 2: Quality of Life: Percentage of participants with DLQI ≥4 at baseline (Part 1) achieving ≥4 point improvement in DLQI at Week 36","definition_or_measurement_approach":"Proportion with baseline DLQI ≥4 achieving ≥4-point improvement at Week 36."}
• {"endpoint_text":"- PART 2: Quality of Life: Percentage of participants with cDLQI ≥6 at baseline (Part 1) achieving ≥6 point improvement in cDLQI at Week 36","definition_or_measurement_approach":"Proportion with baseline cDLQI ≥6 achieving ≥6-point improvement at Week 36."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Proportion with baseline sleep-loss ≥2 achieving ≥2-point improvement at Week 36."}
• {"endpoint_text":"- PART 2: Disease Control: Percentage of participants with POEM ≥4 at baseline (Part 1) achieving ≥4 point improvement in POEM at Week 36","definition_or_measurement_approach":"Proportion with baseline POEM ≥4 achieving ≥4-point improvement at Week 36."}

Denmark

Earliest CTIS Part Ii Submission Date

19-04-2024

Latest Decision Or Authorization Date

13-05-2024

Processing Time Days

24

Number Of Sites

4

Number Of Participants

30

Sweden

Earliest CTIS Part Ii Submission Date

16-04-2024

Latest Decision Or Authorization Date

16-05-2024

Processing Time Days

30

Number Of Sites

2

Number Of Participants

10

Italy

Earliest CTIS Part Ii Submission Date

11-01-2024

Latest Decision Or Authorization Date

30-08-2024

Processing Time Days

232

Number Of Sites

15

Number Of Participants

90

France

Earliest CTIS Part Ii Submission Date

29-07-2024

Latest Decision Or Authorization Date

05-08-2024

Processing Time Days

7

Number Of Sites

28

Number Of Participants

192

Spain

Earliest CTIS Part Ii Submission Date

17-04-2024

Latest Decision Or Authorization Date

13-05-2024

Processing Time Days

26

Number Of Sites

35

Number Of Participants

180

Austria

Earliest CTIS Part Ii Submission Date

20-02-2024

Latest Decision Or Authorization Date

21-05-2024

Processing Time Days

91

Number Of Sites

4

Number Of Participants

20

Primary sponsor

Full Name

Almirall S.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

Extensive trial operational responsibilities (multiple sponsorDuties codes listed in the dossier).

Name

Almac Clinical Services Limited

Responsibilities

Clinical services (sponsor duties codes listed); specific role in dossier: code 14.

Third parties

• {"country":"United States","full_name":"Fulgent Genetics Inc.","duties_or_roles":"Biomarker testing and storage","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Labcorp Early Development Laboratories Inc.","duties_or_roles":"PK and ADA testing and storage","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient Reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"Biomarker testing and storage","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Multiple trial operational roles (codes provided in dossier)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Precision For Medicine Inc.","duties_or_roles":"Skin biopsy testing and storage","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}