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.

Phase 3

Conditions: eczema
inflammation of the skin
10014982

Registration Number: NL-OMON52148

Lead Sponsor: Almirall

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 18

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*2) 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 mid-potency
TCS for
at least 4 weeks, or for the maximum duration recommended by the product
prescribing
information (eg, 14 days for high/very-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)

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 washout 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 18 weeks after the study treatment is
discontinued
8. History of anaphylaxis as defined by the Sampson criteria*40
9. Regular use (more than 2 visits per week) of a tanning booth/parlour 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 aetiology
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
ch