Clinical trial NCT05969730: Baricitinib Versus Azathioprine in Patients With Moderate-to-Severe Atopic Dermatitis
Official title: Efficacy and Safety of Baricitinib Versus Azathioprine in Combination With Topical Corticosteroids For Patients With Moderate-to-Severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Atopic Dermatitis
Keywords: Baricitinib
Azathioprine
Atopic Dermatitis
Moderate-to-Severe Atopic Dermatitis
Lead sponsor: Mazandaran University of Medical Sciences
Sponsor class: OTHER
First posted: 2023-08-01
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: BAAZ-AD-IR is a single-center, open-label, randomized trial which will be conducted in Iran. Patients who meet eligibility criteria will randomize (1:1) to receive baricitinib 4 mg daily or azathioprine 1.5-2.5 mg/kg for 12 weeks. All patients will receive emollient daily. Four weeks prior to randomization, patients will discontinue tropical and systemic treatments for atopic dermatitis and will not be allowed to use them during the study. The drugs will be prescribed at visit 1 (randomization day, or four weeks after screening). All demographics and baseline information will be gathered at visit 1. Six weeks after visit 1, visit 2 will be scheduled for each patient. At visit 2, patients will be followed up. Twelve weeks after visit 1, visit 3 will be scheduled, and final assessments will be done.
Primary purpose: TREATMENT

Brief summary: Atopic dermatitis, which is also known as atopic eczema, is a common inflammatory and chronic skin disease that is characterized by severe recurrent erythematous and pruritic lesions. Patients suffer from decreased quality of life and poor work productivity due to the disease complications like persistent scratching, skin pain, skin damage, sleep disturbances, and social/emotional distress. In the United States (US), the prevalence of adults with atopic dermatitis ranges from 5% to 10%.

The mainstay treatment for atopic dermatitis is emollient and tropical corticosteroids which could be efficient for less severe atopic dermatitis patients but moderate to severe patients usually need additional therapies like phototherapy or systemic medications.

It is revealed that Janus kinase signal transducers and activators of transcription (JAK-STAT) pathway has a prominent role in the development and progression of atopic dermatitis. JAK1/JAK2 inhibitor, baricitinib is a new-class orally available drug that is approved for systemic treatment of adult patients with moderate to severe atopic dermatitis. In the phase III clinical trial baricitinib 2-mg and 4-mg were shown efficient results as monotherapy of adult patients with moderate to severe atopic dermatitis who have an inadequate response to topical corticosteroids (TCS).

Azathioprine is an immunosuppressant and antimetabolite agent interferes with the formation of lymphocytes, and suppresses prostaglandin synthesis, both of which are implicated in the inflammation associated with eczema. Azathioprine can be used (off-label) for moderate to severe atopic dermatitis patients. Multiple studies have demonstrated that azathioprine might be effective for patients with moderate-to-severe atopic dermatitis. Azathioprine is usually prescribed when cyclosporine is either contraindicated or not effective.

This trial will be conducted to test the hypothesis that baricitinib 4-mg daily in combination with TCS is superior to azathioprine 1.5-2.5 mg/kg a day in combination with TCS for moderate-to-severe AD at week 12 in terms of efficacy and safety.


Eligibility criteria: Inclusion criteria

1. Patients with minimum age of 18 years and maximum 75 years at the time of informed consent
2. Patients who can read, understand, and provide written informed consent
3. Individuals with atopic dermatitis who have had a diagnosis for at least 12 months before to screening, as defined by the American Academy of Dermatology: Guidelines of care for the management of atopic dermatitis; Section 1. Diagnosis and assessment of atopic dermatitis \[14\].
4. Patients with moderate to severe atopic dermatitis which is defined as having Eczema Area and Severity Index (EASI) ≥ 16, validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) ≥ 3, and body surface area (BSA) affected ≥10%
5. Individuals who have a documented history of insufficient response to topical treatments (at least a moderate potency topical corticosteroids and/or cyclosporine for at least 4 weeks or the maximum duration recommended for the product prescribed) within the 6 months before screening determined by a dermatologist.
6. Patients who accept to discontinue using (1) oral systemic corticosteroids, (2) systemic immunomodulators such as methotrexate, cyclosporine, and mycophenolate mofetil, and (3) any other systemic therapy used to treat atopic dermatitis (approved or off-label use), for at least 4 weeks before randomization and throughout the study.
7. Patients who accept to discontinue (1) immune modulators (e.g., tacrolimus or pimecrolimus) (2) Topical phosphodiesterase type 4 (PDE-4) inhibitor (crisaborole) (3) sedating antihistamines (both old and new generations) (4) phototherapy, includes therapeutic phototherapy (psoralen plus ultraviolet A, ultraviolet B), excimer laser as well as self-treatment with tanning beds, at least 2 weeks prior to randomization.
8. Patients who agree to use emollients daily for at least 14 days before randomization and who agree to continue using emollients daily during the treatment period.
9. Patients undergoing chronic therapies to improve sleep should be on a stable dosage for at least 2 weeks before screening. Antihistamines with sedative effects are not approved.

Exclusion criteria

1. Patients who are currently suffering from or have a history of any concurrent skin disorders that would interfere with assessments of the study medication's effect on atopic dermatitis. For example, psoriasis or lupus erythematosus or eczema herpeticum, or erythrodermic, refractory, or unstable skin disease, including, but not limited, eczema that requires hospitalizations and/or intravenous treatment for skin infections.
2. Patients who have a known hypersensitivity to baricitinib or azathioprine or any component of these investigational products
3. Patients with any major concomitant disease that is expected to need the administration of systemic corticosteroids, such as unstable chronic asthma, or who otherwise interfere with trial participation or require active regular monitoring.
4. Patients who have been treated (1) Treatment with azathioprine in the previous 3 months (2) Having an experience of treatment with any oral JAK inhibitors including baricitinib \< 4 weeks prior to randomization (3) Fusion proteins that target inflammatory pathways or monoclonal antibodies for less than 5 half-lives before randomization (4) Any parenteral corticosteroid administered by intramuscular/intravenous/intra-articular injection within 6 weeks before randomization or is anticipated to require a parenteral injection of corticosteroids during the study (5) probenecid at the time of randomization that cannot be discontinued for the duration of the study
5. Patients who have uncontrolled hypertension (repeated systolic blood Pressure \>160 mmHg or diastolic blood pressure \>100 mmHg) in a seated position.
6. Patients who have had any major surgery within 8 weeks before screening or will require major surgery during the study
7. Patients who are immunocompromised and have unacceptable risk for taking part in the trial.
8. Patients who have recently experienced myocardial infarction (MI) , or stroke, or venous thromboembolism (VTE) or recurrent VTE (≥2) , or unstable ischemic heart disease, or New York Heart Association Stage III/IV heart failure
9. Patients who have a history of or are currently suffering from any major and/or unstable disease that might provide an unacceptable risk while taking an investigational medication or interfere with data interpretation including but not limited mentally incompetent, current active pancreatitis, cardiovascular, endocrine, respiratory, gastrointestinal, hepatic, hematological, lymphoproliferative, neurological, or neuropsychiatric disorders.
10. Patients with a recent or present clinically significant viral, bacterial, fungal, or parasitic infection (including, but not limited, HIV, TB, Viral hepatitis)
11. Patients who have been exposed to a live vaccine 12 weeks before randomization, or are likely to require/receive a live vaccine throughout the course of the trial
12. Patients who have a history of persistent alcoholism, intravenous drug addiction, or other illicit substance usage during the last 2 years.
13. Patients who have a history of organ transplantation
14. Patients who have donated more than one unit of blood in the 4 weeks before screening or who intend to donate blood during the trial.
15. Patients who are Pregnant/lactating or planning to become pregnant during the study period (men and women)
16. Have any of the following specific abnormalities on screening laboratory tests:

    1. AST or ALT ≥2x upper limit of normal (ULN)
    2. Alkaline phosphatase (ALP) ≥2x ULN
    3. Total bilirubin ≥1.5x ULN
    4. Hemoglobin \<10.0 g/dL (100.0 g/L)
    5. Total white blood cell count \<2500 cells/μL (\<2.50x103/μL or \<2.50 GI/L)
    6. Neutropenia (absolute neutrophil count \[ANC\] \<1200 cells/μL) (\<1.20x103/μL or \<1.20 GI/L)
    7. Lymphopenia (lymphocyte count \<750 cells/μL) (\<0.75x103/μL or \<0.75 GI/L)
    8. Thrombocytopenia (platelets \<100,000/μL) (\<100x103/μL or \<100 GI/L) i. eGFR \<40 mL/min/1.73 m2 (Chronic Kidney Disease Epidemiology Collaboration equation \[CKD-EPI\] Creatinine 2009 equation).

Primary outcomes:
measure: Eczema Area and Severity Index (EASI)
timeFrame: 12 weeks
Secondary outcomes:
measure: Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD)
timeFrame: 12 weeks
measure: SCORing Atopic Dermatitis (SCORAD)
timeFrame: 12 weeks
measure: Body surface area affected (BSA-Affected)
timeFrame: 12 weeks
measure: Dermatology Life Quality Index (DLQI)
timeFrame: 12 weeks
measure: Itch Numeric Rating Scale (Itch NRS)
timeFrame: 12 weeks
measure: Skin Pain Numeric Rating Scale (Skin Pain NRS)
timeFrame: 12 weeks
measure: Atopic Dermatitis Sleep Scale (ADSS)
timeFrame: 12 weeks
measure: Patient-Oriented Eczema Measure (POEM)
timeFrame: 12 weeks
measure: Hospital Anxiety Depression Scale (HADS)
timeFrame: 12 weeks
measure: Adverse Events (Safety assessment)
timeFrame: Throughout the study
Other outcomes:
Locations:
city: Sari
country: Iran, Islamic Republic of
facility: Iran
state: Mazandaran
Study officials:
References:
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