Study of Baricitinib in adult patients with Atopic Dermatitis

• Register: CTRI
• Last refreshed on: 9 January 2023
• Main ID: CTRI/2018/02/011983
• Date of registration: 19-02-2018
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company India Pvt Ltd
• Public title: Study of Baricitinib in adult patients with Atopic Dermatitis
• Scientific title: Protocol I4V-MC-JAHL:A Multicenter, Randomized, Double-Blind,Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib in Adult Patients with Moderate to Severe Atopic Dermatitis
• Date of first enrolment: 15-03-2018
• Target sample size: 600
• Recruitment status: Completed
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=22985
• Study type: Interventional
• Study design: Randomized, Parallel Group, Placebo Controlled Trial Method of generating randomization sequence:Stratified randomization Method of allocation concealment:Centralized Blinding and masking:Participant and Investigator Blinded
• Phase: Phase 3

Countries of recruitment

Canada, Czech Republic, France, Germany, India, Italy, Japan, Mexico, Russian Federation, Taiwan, United States of America

Contacts

• Name: Dr Rohit Arora
• Affiliation: Eli Lilly and Company (India) Pvt. Ltd.

• Name: Dr Rajeev Sharan Shrivastava
• Affiliation: Eli Lilly and Company (India) Pvt. Ltd.

Key inclusion & exclusion criteria

Inclusion criteria: [1] are at least 18 years of age at the time of informed consent.

[2] are able to read, understand, and give documented (electronic or paper signature) informed consent.

[3] have a diagnosis of AD at least 12 months prior to screening, as defined by the

American Academy of Dermatology: Guidelines of care for the management

of AD; Section 1. Diagnosis and assessment of atopic dermatitis

[4] have moderate to severe AD, including all of the following:

a. Eczema Area and Severity Index (EASI) score >=16 at screening (Visit 1)

and at randomization (Visit 2)

b. IGA score of >=3 at screening (Visit 1) and at randomization (Visit 2)

c. >=10% of BSA involvement at screening (Visit 1) and at randomization(Visit 2).

[5] have a documented history by a physician and/or investigator of inadequate response to existing topical medications within 6 months preceding screening,or history of intolerance to topical therapy as defined by at least 1 of the

following:

a. inability to achieve good disease control defined as mild disease or better(e.g., IGA <=2) after use of at least a medium potency TCS for at least 4 weeks, or for the maximum duration recommended by the product prescribing information (e.g., 14 days for super-potent TCS), whichever is shorter. Topical corticosteroids may be used with or without TCNIs.

b. Patients who failed systemic therapies intended to treat AD within 6 months preceding screening, such as cyclosporine, methotrexate,

azathioprine, mycophenolate mofetil will also be considered as a surrogate for having inadequate response to topical therapy.

c. documented history of clinically significant adverse reactions with the use of TCS such as skin atrophy, allergic reactions, systemic effects that in the opinion of the investigator outweigh the benefits of retreatment.

[6] agree to discontinue use of the following excluded medications/treatments for

at least 4 weeks prior to randomization (Visit 2) and throughout the study:

a. systemic corticosteroids and leukotriene inhibitors

b. systemic immunomodulators, including, but not limited to, cyclosporine,methotrexate, mycophenolate mofetil, and azathioprine

c. sedating antihistamines, including, but not limited to, alimemazine, chlorphenamine, clemastine, cyproheptadine, diphenhydramine,

hydroxyzine, ketotifen, and promethazine

Note: Patients may use newer, less sedating antihistamines (e.g.,fexofenadine, loratadine, cetirizine).

d. any other systemic therapy used to treat AD or symptoms of AD(approved or off-label use)

e. phototherapy, includes therapeutic phototherapy (psoralen plus ultraviolet-A, ultraviolet-B), excimer laser as well as self-treatment with tanning beds.

[7] agree to discontinue use of the following excluded medications for at least 2 weeks prior to randomization (Visit 2) and throughout the study:

a. TCS or topical immune modulators (e.g., tacrolimus or pimecrolimus)

b. Topical phosphodiesterase type 4 (PDE-4) inhibitor (crisaborole)

c. Topical JAK inhibitor (e.g., tofacitinib or ruxolitinib) and/or any other

investigative topical treatments.

[8] have applied emollients daily for at least 14 days prior to randomization and agree to use emollient daily throughout the treatment period.

[9] Patients who are receiving chronic treatments to improve sleep sh
Exclusion criteria: [1] are currently experiencing or have a history of other concomitant skin conditions (e.g., psoriasis or lupus erythematosus) that would interfere with evaluations of the effect of study medication on AD.

[2] patients who, in the opinion of the investigator, are currently experiencing or

have a history of erythrodermic, refractory, or unstable skin disease that requires frequent hospitalizations and/or intravenous treatment for skin infections that may interfere with participation in the study.

[3] a history of eczema herpeticum within 12 months prior to screening.

[4] a history of 2 or more episodes of eczema herpeticum in the past.

[5] patients who are currently experiencing a skin infection that requires treatment, or is currently being treated, with topical or systemic antibiotics.

[6] have any serious concomitant illness that is anticipated to require the use of systemic corticosteroids or otherwise interfere with study participation or require active frequent monitoring (e.g., unstable chronic asthma).

[7] have been treated with the following therapies:

a. monoclonal antibody (e.g., ustekinumab, omalizumab, dupilumab) for less than 5 half-lives prior to randomization.

b. received prior treatment with any oral JAK inhibitor (e.g., tofacitinib,ruxolitinib)

c. received any parenteral corticosteroid administered by intramuscular or

intravenous injection within 2 weeks prior to study entry (Visit 1) or

within 6 weeks prior to planned randomization (Visit 2) or are anticipated

to require parenteral injection of corticosteroids during the study.

d. have had an intra-articular corticosteroid injection within 2 weeks prior to

study entry (Visit 1) or within 6 weeks prior to planned randomization (Visit 2).

[8] are largely or wholly incapacitated permitting little or no self-care, such as

being bedridden.

[9] have uncontrolled arterial hypertension characterized by a repeated systolic

blood pressure >160 mm Hg or diastolic blood pressure >100 mm Hg in a seated position.

[10] have had any major surgery within 8 weeks prior to screening or will require

major surgery during the study that, in the opinion of the investigator in

consultation with Lilly or its designee, would pose an unacceptable risk to the

patient.

[11] are immunocompromised and, in the opinion of the investigator, at an unacceptable risk for participating in the study.

[12] have experienced any of the following within 12 weeks of screening: venous

thromboembolic event (VTE), myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart

failure.

[13] have a history of recurrent (>= 2) VTE or are considered at high risk of VTE as deemed by the investigator.

[14] have a history or presence of cardiovascular, respiratory, hepatic,

gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric

disorders or any other serious and/or unstable illness that, in the opinion of the

investigator, could constitute an unacceptable risk when taking investigational product or interfere with the interpretation of data.

[15] have a history of lymphoproliferative disease; or have signs or symptoms

suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Adult Patients with Moderate to Severe Atopic Dermatitis Health Condition 2: L209- Atopic dermatitis, unspecified

Intervention(s)

Intervention1: Baricitinib 1-mg once daily (QD), 2-mg QD, and 4-mg QD: Study I4V-MC-JAHL (JAHL) is a Phase 3, multicenter, randomized, double-blind,
placebo-controlled, parallel-group, outpatient study evaluating the efficacy and safety of baricitinib 1-mg once daily (QD), 2-mg QD, and 4-mg QD as compared to placebo.Approximately 600 patients â?¥18 years of age who have responded inadequately to or who are
intolerant to topical therapy will be randomized at a 2:1:1:1 ratio to receive placebo QD,
baricitinib 1-mg QD, baricitinib 2-mg QD, or baricitinib 4-mg QD (240 patients in the placebo
group; 120 patients in each baricitinib treatment group).
Control Intervention1: Placebo: Patients who meet all criteria for enrollment will be randomized in a 2:1:1:1 ratio (placebo,
baricitinib 1-mg; baricitinib 2-mg; baricitinib 4-mg) to double-blind treatment at Visit 2
(Week 0). Randomization will be stratified by geographic region (North America [NA], Europe
[EU], Japan [JPN], rest-of-world [ROW]) and disease severity at baseline (IGA 3 vs. 4).

Primary Outcome(s)

To test the hypothesis that baricitinib 4-mg QD is

superior to placebo in the treatment of patients with

moderate to severe AD.Timepoint: Proportion of patients achieving IGA of 0 or 1 with

a â?¥2-point improvement at Week 16.

Secondary Outcome(s)

To compare the efficacy of baricitinib 1-mg QD,

2-mg QD, or 4-mg QD to placebo in AD during the

16-week double-blind placebo-controlled treatment

period as assessed by patient-reported outcome

measures.Timepoint: 1.Proportions of patients achieving a 4-point

improvement in Itch NRS at 1 week, 2 weeks,4 weeks, and 16 weeks

2.Mean change from baseline in the score of Item 2

of the ADSS at 1 week and 16 weeks

3.Mean change from baseline in Skin Pain NRS at 16 weeks.

To compare the efficacy of baricitinib 1-mg QD,

2-mg QD, or 4-mg QD to placebo in AD during the

16-week double-blind placebo-controlled treatment

period as measured by improvement in signs and

symptoms of AD.Timepoint: 1. Poportion of patients achieving EASI75 at

16 weeks

2. Proportion of patients achieving EASI90 at

16 weeks

3. Percent change from baseline in EASI score at

16 weeks.

4. Proportion of patients achieving SCORAD75 at

16 weeks.

To test the hypothesis that baricitinib 2-mg QD or

baricitinib 1-mg QD is superior to placebo in the

treatment of patients with moderate to severe ADTimepoint: Proportion of patients achieving IGA of 0 or 1 with

a â?¥2-point improvement at Week 16.

Secondary ID(s)

Protocol I4V-MC-JAHL dated 29-Jun-2017

Source(s) of Monetary Support

Eli Lilly and Company (India) PVT LTD, Plot No. 92, Sector-32, Gurgaon, Haryana - 122001

Ethics review

Status: Approved
Approval date: 22/01/2018
Contact:

Institutional Ethics Committee, King George Hospital

Status: Approved
Approval date: 06/02/2018
Contact:

Panchshil Institutional Ethics Committee

Status: Approved
Approval date: 09/02/2018
Contact:

Ethics Committee , Jehangir Clinical Development Centre Pvt. Ltd

Status: Approved
Approval date: 22/02/2018
Contact:

Ethics Committee, M.S. Ramaiah Medical College and Hospitals

Status: Approved
Approval date: 07/03/2018
Contact:

Ethics Committee, MGM Institute of Health Sciences

Status: Approved
Approval date: 26/03/2018
Contact:

Institutional Ethics Committee for Human Research, Medical College

Status: Approved
Approval date: 27/03/2018
Contact:

Chennai Meenakshi Multispeciality Hospital Ethics Committee

Status: Approved
Approval date: 30/03/2018
Contact:

Institutional Ethics Committee, Principle office, Gandhi Medical College

Status: Approved
Approval date: 31/03/2018
Contact:

Ethics Committee, Sir Ganga Ram Hospital

Status: Approved
Approval date: 06/04/2018
Contact:

Institutional Ethics Committee, Poona Medical Research Foundation

Status: Approved
Approval date: 26/04/2018
Contact:

The Institutional Ethics Committee, B J Medical College and Civil Hospital

Status: Approved
Approval date: 06/07/2018
Contact:

Institutional Ethics Committee-I, Seth G. S. Medical College and K. E. M. Hospital

Status: Approved
Approval date: 28/10/2018
Contact:

Institutional Ethics Committee, M.V. Hospital

Status: Approved
Approval date: 05/11/2018
Contact:

Institutional Ethics Committee, Dr D Y Patil Medical College

Status: Approved
Approval date: 10/12/2018
Contact:

Institute Ethics Committee, All India Institute of Medical Sciences

Results

• Date Completed: 16/08/2019