Clinical Trials Register

Summary
EudraCT Number:	2021-002967-23
Sponsor's Protocol Code Number:	M-17923-30
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:
Date on which this record was first entered in the EudraCT database:	2021-08-18
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2021-002967-23

A.3

Full title of the trial

A Randomised, Double-Blind, Placebo-Controlled Phase 3 Clinical Trial to Assess the Efficacy and Safety of Lebrikizumab in Combination With Topical Corticosteroids in Adult and Adolescent Patients With Moderate-To-Severe Atopic Dermatitis That Are Not Adequately Controlled With Cyclosporine or For Whom Cyclosporine is Not Medically Advisable

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Efficacy and safety of lebrikizumab in patients with AD not adequately controlled or non-eligible for cyclosporine

A.3.2

Name or abbreviated title of the trial where available

ADvantage

A.4.1

Sponsor's protocol code number

M-17923-30

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Almirall, S.A.
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Almirall, S.A.
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Almirall, S.A.
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	Ronda General Mitre, 151
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08022
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34932913545
B.5.6	E-mail	gco@almirall.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Lebrikizumab
D.3.2	Product code	LY3650150
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	lebrikizumab
D.3.9.2	Current sponsor code	LY3650150
D.3.9.3	Other descriptive name	LEBRIKIZUMAB
D.3.9.4	EV Substance Code	SUB31913
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	125
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection in pre-filled syringe
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

atopic dermatitis

E.1.1.1

Medical condition in easily understood language

atopic dermatitis

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

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the efficacy of lebrikizumab compared with placebo in patients not adequately controlled with cyclosporine or for whom cyclosporine is not medically advisable up to Week 16

E.2.2

Secondary objectives of the trial

To evaluate the efficacy in patients not adequately controlled with cyclosporine or for whom cyclosporine is not medically advisable between Week 16 up to Week 52

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Adults and adolescents (aged ≥12 to <18 years at the time of ICF/IAF and weighing ≥40 kg)
2. Chronic AD (according to Hanifin and Rajka Criteria) that has been present for ≥1 year before the Screening visit
3. EASI score ≥16 at the 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 Baseline visit
6. Documented history by a physician of an inadequate response to existing topical medications within 6 months before Screening, defined as: inability to achieve good disease control (eg, not able to achieve IGA ≤2) after use of at least a moderate-potency TCS for at least 4 weeks, or for the maximum duration recommended by the product prescribing information (eg, 14 days for ultra-high-potency TCS), whichever is shorter
7. Documented history by a physician of either:
a) No previous CsA exposure and not currently a candidate for CsA treatment because of
i. medical contraindications (eg, uncontrolled hypertension on medication), or
ii. use of prohibited concomitant medications (eg, statins, digoxin, macrolide antibiotics, barbiturates, anti-seizure drugs, nonsteroidal anti-inflammatory drugs, diuretics, angiotensin-converting-enzyme inhibitors, St John’s Wort, etc.), or
iii. increased susceptibility to CsA-induced renal damage (elevated creatinine) and/or liver damage (elevated function tests results), or
iv. increased risk of serious infections, or
v. hypersensitivity to CsA active substance or excipients
OR:
b) Previous exposure to CsA; CsA treatment should not be continued or restarted because of
i. intolerance and/or unacceptable toxicity (eg, elevated creatinine, elevated liver function test results, uncontrolled hypertension, paraesthesia, headache, nausea, hypertrichosis); or
ii. requirement for CsA at doses or durations beyond those specified in the prescribing information or inadequate response
8. Completed electronic diary (eDiary) entries for pruritus and sleep-loss for a minimum of 4 of 7 days before randomisation
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 to use a highly effective contraceptive method during the treatment period and for at least 18 weeks after the last dose of lebrikizumab or placebo
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 WOCBP
12. Patient must provide signed ICF. Adolescent patients 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)

E.4

Principal exclusion criteria

1. Participation in a prior lebrikizumab clinical study
2. Treatment with IL-4 or IL-13 antagonists biological therapies before the Baseline visit.
Exception: previous treatment with dupilumab will be allowed in a subset of patients. A wash-out of at least 8 weeks before the Baseline visit will be required for this subpopulation
3. Treatment with TCS within 1 week before the Baseline visit
4. Treatment with topical calcineurin inhibitors, phosphodiesterase-4 inhibitors such as crisaborole, or cannabinoids within 2 week before the Baseline visit
5. Treatment with any of the following agents within 4 weeks before the Baseline visit:
a. Immunosuppressive/immunomodulating drugs (eg, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, interferon-γ, JAK inhibitors, azathioprine, methotrexate, etc.)
b. Phototherapy and photochemotherapy (PUVA) for AD
6. Treatment with the following before 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 but not limited to rituximab, within 6 months;
c. Other biologics within 16 weeks or 5 half-lives (if known) , whichever is longer
7. Treatment with a live (attenuated) vaccine within 12 weeks of the Baseline visit, planned during the study, or 12 weeks after the study treatment is discontinued
8. History of anaphylaxis as defined by the Sampson criteria
9. Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the Screening visit
10. Uncontrolled chronic disease that might require bursts of oral corticosteroids, eg, comorbid 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)
11. Have had any of the following types of infection within 3 months of Screening or develop any of these infections before randomisation:
a. Serious (requiring hospitalisation, and/or IV or equivalent oral antibiotic treatment);
b. Opportunistic (as defined in Winthrop et al. 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)
12. Have a current or chronic infection with hepatitis B virus
13. Have a current infection with hepatitis C virus (ie, positive for hepatitis C RNA)
14. Have known liver cirrhosis and/or chronic hepatitis of any etiology
15. Diagnosed active endoparasitic infections 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 judgment
17. History of HIV infection or positive HIV serology at Screening
18. In the Investigator’s opinion, any clinically significant laboratory test results from the chemistry, haematology, or urinalysis tests obtained at the Screening visit
19. Presence of skin comorbidities that may interfere with study assessments
20. 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
21. 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
22. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study
23. Have had an important side effect to TCS (eg, intolerance to treatment, hypersensitivity reactions, significant skin atrophy, and systemic effects), as assessed by the Investigator or treating physician that would prevent further use

E.5 End points

E.5.1

Primary end point(s)

Percentage of patients achieving EASI 75 (≥75% reduction from Baseline in EASI score) at Week 16

E.5.1.1

Timepoint(s) of evaluation of this end point

week 16

E.5.2

Secondary end point(s)

-Percentage of patients achieving IGA 0/1 and 2-point improvement at Week 16
-Percentage of patients achieving a 4- point improvement Pruritus NRS at Week 16
- % of patients achieving EASI 90 at Week 16
- % patients achieving EASI 75, EASI 90 and EASI 50 (by visit up to Week 16)
- Change from Baseline BSA by visit up to Week 16
- Change from Baseline SCORAD by visit up to Week 16
- Change from Baseline Pruritus NRS by visit up to Week 16
- Change from Baseline sleep loss by visit up to Week 16
- Change from Baseline POEM by visit up to Week 16
- Change from Baseline DLQI/CDLQI by visit up to Week 16
- % patients achieving a 4-point improvement DLQI/CDLQI by visit up to Week 16
- Proportion of TCS-free days from Baseline by visit up to Week 16
-Time to TCS-free use (days) up to Week 16
- Change from Baseline Skin Pain NRS by visit up to Week 16
- % patients achieving a 4-point improvement Skin Pain NRS at Week 16

E.5.2.1

Timepoint(s) of evaluation of this end point

week 16

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

2 part of the study - first double-blind, second part open label

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

The “end of trial” is defined as the date when all patients randomised in the trial complete follow-up contact (either Treatment Completers or those Prematurely Discontinued), or are lost to follow-up and have not been able to be contacted, and will be communicated to Competent Authorities and the independent ethics committee (IEC) in due time according to local regulations.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

312

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

312

F.4.2.2

In the whole clinical trial

312

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Once the last dose of study drug is taken (eg, the last visit at which the patient takes IMP [Week 52]) and related trial measurements are completed, patients should continue to take their usual medications, also allowed during the trial, and may resume other medications that were interrupted before trial enrolment as deemed appropriate by the Investigator.
The study drug is for experimental use only, and there are other therapies available to treat the disease.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-11-03

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials