Ruxolitinib Clinical Trials

What Is Ruxolitinib?

Ruxolitinib is an FDA-approved medication for myelofibrosis and chronic graft-versus-host disease (cGVHD) that has not responded to prior treatments. It is a type of drug known as a Janus kinase (JAK)1 and JAK2 inhibitor. This means it works by blocking specific signaling pathways within cells that can contribute to inflammation, immune responses, and the growth of certain abnormal blood cells.

In addition to its approved uses, Ruxolitinib is being studied in 388 clinical trials with 43,693 participants for a wide range of other conditions. These include other blood cancers like polycythemia vera, essential thrombocythemia, and acute myeloid leukemia. It is also being investigated for various inflammatory and autoimmune conditions such as atopic dermatitis, vitiligo, acute graft-versus-host disease, alopecia areata, and psoriasis. Other areas of research include certain solid tumors, lymphomas, and even COVID-19. The earliest trial for ruxolitinib began on 2002-08-26, and new studies are planned until at least 2026-06-01.

Uses and Conditions Under Study

Ruxolitinib is being investigated for a broad spectrum of conditions, primarily focusing on blood disorders, autoimmune diseases, and certain cancers. Clinical trials are exploring its potential in various settings:

• Myeloproliferative Neoplasms (MPN): Ruxolitinib is FDA-approved for myelofibrosis (MF), a rare blood cancer characterized by bone marrow scarring and an enlarged spleen. It is being studied in 87 trials for myelofibrosis, including primary and secondary forms, to assess its ability to shrink the spleen and improve symptoms. It is also being evaluated for other MPNs like polycythemia vera (16 trials) and essential thrombocythemia, where it aims to reduce excess blood cells and alleviate patient symptoms.
• Graft-versus-Host Disease (GVHD): As an FDA-approved treatment for chronic GVHD that has failed prior therapies, ruxolitinib is also being studied for acute GVHD and for preventing GVHD after bone marrow or stem cell transplantation. This complication can be life-threatening, and ruxolitinib's immune-modulating effects are thought to be beneficial.
• Dermatological and Autoimmune Conditions: The drug is under investigation for a range of skin and autoimmune disorders, including atopic dermatitis (16 trials), vitiligo (10 trials), alopecia areata, and psoriasis. In these conditions, ruxolitinib's ability to inhibit JAK pathways may help calm overactive immune responses that cause inflammation and tissue damage.
• COVID-19: Ruxolitinib is being explored in 7 trials for its potential to treat severe COVID-19. Researchers hypothesize that its JAK-inhibiting properties could help to reduce the severe systemic inflammation, often referred to as a "cytokine storm," associated with critical COVID-19 cases.
• Other Cancers and Malignancies: Beyond MPNs, ruxolitinib is being studied in various other cancers, including acute myeloid leukemia (9 trials), other leukemias (7 trials), lymphomas, multiple myeloma, and several solid tumors such as gliomas, glioblastomas, colorectal cancer, pancreatic adenocarcinoma, and breast cancer. These studies aim to determine if blocking JAK/STAT pathways can inhibit cancer cell growth and improve treatment outcomes, often in combination with other therapies.

Dosing

Ruxolitinib is available in both oral tablet and topical cream forms, with various strengths studied depending on the condition being treated.

Oral Tablets:

• Ruxolitinib tablets are typically taken by mouth, often twice daily (BID), approximately 12 hours apart.
• Doses studied range widely, including 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 50 mg, 100 mg, and 200 mg.
• For myelofibrosis, a common FDA-approved dose is 20 mg twice daily. Dosing for myelofibrosis can also be adjusted based on platelet counts: 5 mg twice a day for platelets under 30,000/µL, 10 mg twice a day for platelets between 30,000/µL and 50,000/µL, and 15 mg twice a day for platelets above 50,000/µL.
• Some trials have investigated extended-release (SR) formulations, such as 25 mg SR, as well as immediate-release (IR) forms.

Topical Cream:

• Ruxolitinib is also studied as a topical cream, known by the brand name Opzelura, for skin conditions like atopic dermatitis and vitiligo.
• Strengths investigated for the cream include 0.15%, 0.5%, 0.75%, 1.0%, and 1.5%.
• The cream is typically applied to affected skin areas, sometimes once daily (QD) or twice daily (BID), depending on the specific study protocol.

While specific pediatric doses are not detailed, some clinical trials involving ruxolitinib are conducted at children's hospitals, indicating ongoing research into appropriate dosing for younger patients.

Side Effects

In clinical trials, patients taking Ruxolitinib experienced certain side effects more often than those on placebo. The most common side effect was palmar-plantar erythrodysaesthesia syndrome, affecting 38.7% of patients on Ruxolitinib compared to 32.8% on placebo.

Other common side effects included:

• Anemia, reported by 33.9% of patients on Ruxolitinib versus 29.6% on placebo.
• Diarrhea, experienced by 24.5% of patients on Ruxolitinib compared to 19.6% on placebo.
• Thrombocytopenia, affecting 18.2% of patients on Ruxolitinib versus 11.4% on placebo.
• Headache, seen in 11.5% of patients on Ruxolitinib compared to 10.3% on placebo.
• Pyrexia (fever), reported by 9.7% of patients on Ruxolitinib versus 8.6% on placebo.

Some side effects were reported less frequently in patients taking Ruxolitinib compared to placebo. These included fatigue (20.9% on Ruxolitinib vs 23.9% on placebo), nausea (18.4% on Ruxolitinib vs 21.9% on placebo), and abdominal pain (14.9% on Ruxolitinib vs 21.3% on placebo).

Clinical Trial Results

Ruxolitinib for Myelofibrosis

In an open-label study (NCT00509899) for patients with myelofibrosis, including those with post-polycythemia vera or essential thrombocythemia myelofibrosis, Ruxolitinib showed several benefits. Patients experienced an average increase in body weight, ranging from 0.30 kg to 6.60 kg over time, which can be a positive outcome for patients who often experience weight loss with this condition.

Symptom scores for myelofibrosis generally improved. At Week 24, patients receiving 10 mg twice daily saw an average reduction of 4.7 points in their total symptom score, while those on 15 mg twice daily had an average reduction of 5.6 points. Patients taking Ruxolitinib once daily experienced an average reduction of 6.5 points. Additionally, a significant number of patients achieved a reduction in spleen size; for example, between 47.1% and 75.0% of patients across various doses achieved at least a 50% reduction in spleen palpation length. For spleen volume, 40.0% to 48.0% of patients on 15 mg twice daily achieved at least a 35% reduction.

Ruxolitinib for Psoriasis (Topical)

A study (NCT00617994) evaluating topical Ruxolitinib for psoriasis demonstrated improvements in lesion area and severity. Patients in different cohorts experienced substantial reductions in psoriatic lesion area. For instance, one cohort saw an average reduction of 1267.78 cm^2 in treated lesions, compared to a minimal change in control lesions. Similarly, the total lesion severity score for target lesions improved, with reductions ranging from 1.2 to 5.4 points, while control lesions showed less improvement or even slight worsening.

Ruxolitinib for Polycythemia Vera and Essential Thrombocythemia

In a study (NCT00726232) for patients with polycythemia vera (PV) or essential thrombocythemia (ET), Ruxolitinib showed varying effects. For PV, 50% to 58% of participants achieved a confirmed clinical partial or complete response. Patients also reported reductions in PV-related symptoms, with average score decreases ranging from 1.9 to 4.6 points at Week 4, depending on the dose. For ET, 13% of participants on 10 mg twice daily achieved a confirmed clinical partial response, but response rates were lower or zero at other doses. ET symptoms also showed some improvement, with average score decreases ranging from 0.2 to 5.0 points at Week 4.

Ruxolitinib for Prostate Cancer and Multiple Myeloma

In separate studies, Ruxolitinib did not show efficacy for certain other conditions. For androgen-independent metastatic prostate cancer (NCT00638378), no participants showed a prostate-specific antigen response. Similarly, for multiple myeloma (NCT00639002), no participants were identified as responders according to the International Uniform Response Criteria.

Currently Recruiting Trials

Ruxolitinib is currently being investigated in 94 active clinical trials, exploring its potential to treat a wide array of conditions, from various cancers to autoimmune disorders and transplant complications. These studies aim to understand how Ruxolitinib works, its safety, and its effectiveness, often in combination with other treatments.

For patients with metastatic castration-resistant prostate cancer, NCT06616155 is a Phase 1/2 study enrolling 20 participants. This trial evaluates the safety and optimal dose of ruxolitinib when combined with enzalutamide.

Several trials are focused on preventing or treating Graft-versus-Host Disease (GVHD). NCT07025538 is a Phase 1 study at City of Hope Medical Center, enrolling 42 patients with hematopoietic and lymphatic system neoplasms, investigating biomarker-guided ruxolitinib for preventing chronic GVHD after allogeneic hematopoietic cell transplant. A Phase 2 study, NCT07249346, is enrolling 124 participants with leukemia, myelodysplasia, or chronic myelomonocytic leukemia to evaluate low-dose post-transplant cyclophosphamide/tacrolimus/ruxolitinib for GVHD prophylaxis. For older patients with myelofibrosis or myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes, NCT07228624 (Phase 2, 50 patients) tests ruxolitinib before, during, and after hematopoietic cell transplant to prevent GVHD. A large Phase 3 trial, NCT06615050, with an enrollment target of 572, compares ruxolitinib in combination with tacrolimus/methotrexate against a standard regimen for GVHD prevention.

In a Phase 1/2 study (NCT07252050), 24 children and young adults with sickle cell disease are being recruited to determine if adding ruxolitinib to a reduced intensity conditioning regimen can lower the rate of graft failure after haploidentical hematopoietic cell transplant.

For myelofibrosis, Novartis Pharmaceuticals is sponsoring two studies combining pelabresib with ruxolitinib: a Phase 3 study (NCT07357727) enrolling 460 patients with primary, post-polycythemia vera, or post-essential thrombocythemia myelofibrosis, and a Phase 1 study (NCT07340138) in 6 Japanese adult patients. NCT06479135, a Phase 3 study, is enrolling 600 patients to evaluate adding navtemadlin to ruxolitinib for those with a suboptimal response to ruxolitinib alone.

For skin conditions, NCT06804811 is a Phase 3 study enrolling 250 children (6 to <12 years old) to assess the efficacy and safety of ruxolitinib cream for nonsegmental vitiligo. A real-world study (NCT07153666) is also collecting data on ruxolitinib cream in 170 vitiligo patients.

A Phase 2 trial (NCT06991101) is enrolling 190 patients with newly diagnosed glioblastoma to test ruxolitinib in combination with radiation and temozolomide.

Finally, NCT07588139 is a Phase 1 study with 24 healthy adults, evaluating the pharmacokinetics of topical ruxolitinib cream.

Where to Participate

Ruxolitinib clinical trials are broadly accessible, with studies actively recruiting across 520 sites in 226 cities and 42 states. This wide geographic reach ensures that many patients have the opportunity to participate.

The top cities with the most recruiting sites include:

• New York, New York (30 sites)
• Miami, Florida (26 sites)
• Boston, Massachusetts (19 sites)
• Houston, Texas (15 sites)
• Seattle, Washington (12 sites)
• Tampa, Florida (12 sites)
• Columbus, Ohio (12 sites)
• Nashville, Tennessee (11 sites)
• Chicago, Illinois (11 sites)
• Duarte, California (9 sites)

Eligibility for these trials is inclusive, welcoming participants from 0 to 100 years of age, regardless of gender. Many studies also include children, and some specifically recruit healthy volunteers to gather important safety and pharmacokinetic data.

Development Timeline

The journey of Ruxolitinib began on August 26, 2002, with its first clinical trial. Since then, a robust development program has unfolded, encompassing a total of 388 trials and enrolling over 43,693 participants. Early investigations initially explored conditions like IBS-C and hyperphosphatemia.

Over time, the focus significantly broadened, driven by key sponsors like Incyte Corporation, which has sponsored 83 trials, and Novartis Pharmaceuticals, with 25 trials. Ruxolitinib's pipeline expanded to address a diverse range of hematologic malignancies and related complications. It became a significant treatment option for conditions such as Polycythemia Vera, Myelofibrosis, and Essential Thrombocythemia. Its utility further extended to managing transplant-related complications like Graft-versus-host Disease (GVHD) and Hemophagocytic Lymphohistiocytosis.

Beyond blood disorders, Ruxolitinib's therapeutic potential was explored in various autoimmune and inflammatory conditions. This led to studies in Atopic Dermatitis, Vitiligo, Hidradenitis Suppurativa, and Alopecia Areata, often with topical formulations. The drug's development has progressed through all phases, with 158 Phase 2 studies and 53 Phase 3 studies, demonstrating a comprehensive evaluation from early safety assessments to large-scale efficacy confirmations. This extensive research reflects Ruxolitinib's evolution into a versatile treatment for a wide spectrum of complex diseases.