Baricitinib Clinical Trials

What Is Baricitinib?

Baricitinib is an FDA-approved medication for the treatment of moderate to severe Rheumatoid Arthritis and severe pneumonia caused by the coronavirus (COVID-19). This drug works as a Janus kinase 1 and 2 (JAK1/JAK2) inhibitor. By blocking these specific enzymes, baricitinib helps to reduce inflammation in the body.

Beyond its approved uses, baricitinib is currently being investigated in clinical trials for a variety of other conditions. These include inflammatory and autoimmune disorders such as atopic dermatitis, alopecia areata, systemic lupus erythematosus, and primary Sjogren's syndrome. Researchers are also exploring its potential in treating rare diseases like Kohlmeier-Degos and ocular mucous membrane pemphigoid. Furthermore, baricitinib is under study for its effects on HIV-1 viral rebound, depression in people with HIV, and certain neurodegenerative diseases like Alzheimer's and amyotrophic lateral sclerosis. Its anti-inflammatory properties are also being examined for conditions such as intracerebral hemorrhage and immune thrombocytopenia.

Uses and Conditions Under Study

Baricitinib is being investigated for a wide range of conditions, primarily focusing on its ability to modulate the immune system and reduce inflammation.

• Autoimmune and Inflammatory Joint Conditions: Baricitinib is extensively studied for conditions like Rheumatoid Arthritis, with 21 trials. It is also being explored for Systemic Lupus Erythematosus (4 trials), Primary Sjogren's syndrome, Axial Spondylarthritis (ax-SpA), and Calcium Pyrophosphate Deposition disease (CPPD). These conditions involve chronic inflammation and immune system dysfunction, which baricitinib aims to address by inhibiting specific signaling pathways.
• Skin and Pigmentary Disorders: The drug is under investigation for various skin conditions, including Atopic Dermatitis (13 trials) and Alopecia Areata (5 trials), where it may help reduce inflammation and promote hair regrowth. Other skin-related studies involve Vitiligo, Ocular mucous membrane pemphigoid (MMP), and general Skin Diseases (3 trials).
• Infectious Diseases: Baricitinib has been studied for COVID-19, with a total of 15 trials (11 for COVID-19 and 4 for Covid19) exploring its role in managing severe pneumonia and inflammation associated with the virus. Additionally, it is being investigated in people with HIV to understand its effects on viral rebound, viral load, and associated inflammation and depression.
• Other Inflammatory and Rare Conditions: Studies are also underway for Kohlmeier-Degos (K-D), a rare disease causing inflammation and blood clots, and Immune Thrombocytopenia (3 trials), an autoimmune bleeding disorder. Its potential to reduce severe lung injury following intracerebral hemorrhage and to impact inflammatory signaling in neurodegenerative diseases like Alzheimer's and amyotrophic lateral sclerosis is also being examined.

Baricitinib is also studied in Healthy Volunteers (9 trials) and Healthy individuals (3 trials) to understand its safety, pharmacokinetics, and pharmacodynamics in the absence of disease.

Dosing

Baricitinib is primarily studied in tablet form for oral administration. Various strengths have been investigated in clinical trials.

Commonly studied doses for adults include:

• 2 mg once daily (QD)
• 4 mg once daily (QD)

Some trials have also explored higher doses such as 8 mg and 10 mg once daily. For example, one study involved an initial dose of 2 mg once daily for 90 days, with potential titration to 4 mg once daily for another 90 days, depending on safety and appropriateness.

In specific investigational settings, such as for severe lung injury, a dose of 8 mg per kilogram of body weight has been administered enterally (oral or via a gastric tube) once daily for 14 days. This particular dosing regimen was noted to be the same for both adults and children. While most studies indicate once-daily dosing, some investigational regimens have explored twice-daily (BID) administration, such as Baricitinib 0.75 mg/0.5 mg BID. The specific dose and duration of baricitinib treatment vary significantly depending on the condition being studied and the trial design.

Side Effects

In clinical trials, the most common side effect reported by patients taking Baricitinib was nasopharyngitis (common cold symptoms). Across 21 trials involving over 13,000 patients, 9.1% of patients on Baricitinib experienced nasopharyngitis, compared to 7.5% on placebo.

Other common side effects observed in patients taking Baricitinib, compared to those on placebo, include:

• Upper respiratory tract infection: 6.5% of patients on Baricitinib experienced this, compared to 4.8% on placebo.
• Headache: 5.2% of patients on Baricitinib experienced this, compared to 4.4% on placebo.
• Acne: 4.8% of patients on Baricitinib experienced this, compared to 1.4% on placebo.
• Urinary tract infection: 4.4% of patients on Baricitinib experienced this, compared to 3.9% on placebo.
• Increased blood creatine phosphokinase (an enzyme that can indicate muscle damage): 3.1% of patients on Baricitinib experienced this, compared to 1.0% on placebo.
• Herpes zoster (shingles): 2.6% of patients on Baricitinib experienced this, compared to 0.9% on placebo.
• Influenza (flu): 2.4% of patients on Baricitinib experienced this, compared to 1.2% on placebo.

Clinical Trial Results

Rheumatoid Arthritis

In a study of Japanese participants with active rheumatoid arthritis on methotrexate (NCT01469013), Baricitinib showed significant improvements in disease activity and physical function compared to placebo. At Week 12, patients receiving 4 mg Baricitinib had a mean reduction of 2.09 units in their Disease Activity Score (DAS28-CRP), while those on placebo had a reduction of 0.60 units. Physical function, measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI), also improved; patients on 4 mg Baricitinib had a mean reduction of 0.469 units, compared to 0.077 units for placebo. Furthermore, 77% of patients on combined 4 mg and 8 mg Baricitinib achieved an American College of Rheumatology 20% improvement (ACR20) response, compared to 31% on placebo. Long-term data at 64 weeks showed sustained improvement, with 94% of patients on combined 4 mg and 8 mg Baricitinib achieving an EULAR28 response.

Another study compared Baricitinib to adalimumab and placebo in patients with moderate to severe rheumatoid arthritis (NCT01710358). Baricitinib led to a mean reduction of 2.27 units in DAS28-hsCRP, which was greater than adalimumab (-1.98 units) and placebo (-1.01 units). Baricitinib also resulted in a higher ACR20 response rate, with 69.6% of patients achieving this milestone, compared to 61.2% for adalimumab and 40.2% for placebo. The progression of joint damage, measured by the Modified Total Sharp Score (mTSS), was slowed more effectively by Baricitinib (0.35 units) and adalimumab (0.29 units) compared to placebo (0.84 units).

In a trial comparing Baricitinib alone or with methotrexate to methotrexate alone (NCT01711359), Baricitinib in combination with methotrexate showed a greater reduction in DAS28-ESR (mean reduction of 3.06 to 3.22 units) compared to methotrexate alone (mean reduction of 2.20 to 2.32 units). Patients receiving Baricitinib plus methotrexate also had higher ACR20 response rates (72.6% to 78.1%) than those on methotrexate alone (55.7% to 61.9%). Additionally, Baricitinib, both alone and with methotrexate, slowed joint damage progression more than methotrexate alone.

Psoriasis

A Phase 2b study in participants with moderate to severe psoriasis (NCT01490632) evaluated the efficacy of Baricitinib. At Week 12, patients on 10 mg Baricitinib experienced a mean reduction of 13.93 units in Psoriasis Area and Severity Index (PASI) total score, indicating significant improvement in psoriasis severity, compared to a 5.14 unit reduction for placebo. A PASI 75 improvement (at least 75% reduction in PASI score) was achieved by 54.1% of patients on 10 mg Baricitinib, versus 16.7% on placebo. Quality of life, measured by the Dermatology Life Quality Index (DLQI), also improved significantly, with a mean reduction of 5.1 units for 10 mg Baricitinib compared to 1.7 units for placebo. Itch severity, assessed by the Itch Numeric Rating Scale (NRS), decreased by 4.7 units for 10 mg Baricitinib, versus 1.1 units for placebo.

Diabetic Kidney Disease

In a study of participants with diabetic kidney disease (NCT01683409), Baricitinib at a dose of 4 mg/2.75 mg resulted in a mean change from baseline in Urinary Albumin/Creatinine Ratio (UACR) of 0.66 mg/g at Week 24, compared to 1.12 mg/g for placebo. A lower UACR indicates a reduction in albumin in the urine, suggesting an improvement in kidney function.

Currently Recruiting Trials

Baricitinib is currently being investigated in a variety of clinical trials, exploring its potential to treat a wide range of conditions from autoimmune disorders to neurological diseases. These studies aim to understand how Baricitinib works, its safety, and its effectiveness for patients who might benefit from this treatment.

For instance, the National Institute of Allergy and Infectious Diseases (NIAID) is sponsoring a Phase 1 study (NCT07262983) to evaluate the safety and tolerability of Baricitinib in patients with Job Syndrome, particularly those experiencing lupus-like disease or atopic dermatitis. This study plans to enroll 20 participants. Another Phase 1 study (NCT07554222), sponsored by Innovent Biologics, is assessing Baricitinib tablets and IBI3013 in 160 healthy volunteers, as well as in patients with active non-segmental vitiligo and severe alopecia areata.

In the realm of rare diseases, the National Heart, Lung, and Blood Institute (NHLBI) is conducting a Phase 2 trial (NCT06923072) to study Baricitinib in 12 patients with Kohlmeier-Degos Disease who have neurological involvement. Eli Lilly and Company is sponsoring two large Phase 3 trials for type 1 diabetes: one (NCT07222332) enrolling 300 children and adults newly diagnosed with type 1 diabetes to preserve beta cell function, and another (NCT07222137) enrolling 150 at-risk individuals to delay the onset of clinical type 1 diabetes.

Other notable recruiting trials include a Phase 2 study (NCT07003997) by Emory University, enrolling 100 participants to investigate Baricitinib's role in major depressive disorder with high inflammation. Peking Union Medical College Hospital is conducting a Phase 2 trial (NCT06849908) comparing Baricitinib with Adalimumab in 56 patients with intestinal Behçet's Syndrome. For patients with Long COVID, a large Phase 3 trial (NCT06631287) sponsored by Wes Ely is enrolling 550 participants to evaluate Baricitinib's effect on persistent neurological and cardiopulmonary symptoms. Additionally, Eli Lilly and Company is sponsoring a Phase 3 study (NCT05723198) enrolling 595 children aged 6 to less than 18 years with severe or very severe alopecia areata.

Where to Participate

Clinical trials for Baricitinib are widely available, with studies taking place across a broad geographic area to ensure diverse participation. Currently, there are 96 sites in 76 cities across 33 states actively recruiting participants.

The top cities with multiple recruiting sites include:

• Atlanta, Georgia (6 sites)
• Chicago, Illinois (3 sites)
• Cleveland, Ohio (3 sites)
• Portland, Oregon (3 sites)
• Aurora, Colorado (2 sites)
• Charlottesville, Virginia (2 sites)
• San Antonio, Texas (2 sites)
• Jacksonville, Florida (2 sites)
• Austin, Texas (2 sites)
• Philadelphia, Pennsylvania (2 sites)

Eligibility for these trials is broad, welcoming participants of all genders, ranging in age from 0 to 120 years. Many studies also include children, and some specifically recruit healthy volunteers to help understand the drug's effects.

Development Timeline

The journey of Baricitinib in clinical development began with its first trial on November 10, 2011, and continues with studies projected as far as April 28, 2026. To date, a total of 156 trials have been conducted or are underway, involving an impressive 147,315 participants.

Eli Lilly and Company has been a primary driver of Baricitinib's development, sponsoring 51 trials. However, a diverse group of academic institutions and other organizations have also contributed significantly to its research. The development pipeline shows a strong focus on later-stage research, with 48 trials in Phase 2 and 46 trials in Phase 3, indicating a progression towards understanding efficacy and safety in larger patient populations.

Initially, Baricitinib's research focused on conditions like IBS-C and hyperphosphatemia. Over time, its potential expanded dramatically. Key milestones include its investigation for COVID-19, where it has shown promise in treating pneumonia. The drug's application broadened to various autoimmune conditions such as alopecia areata, systemic lupus erythematosus, dermatomyositis, and vitiligo. It also moved into areas like type 1 diabetes, juvenile idiopathic arthritis, and even neurological conditions such as major depressive disorder and traumatic brain injury, showcasing its versatile therapeutic potential.