Apremilast Clinical Trials

What Is Apremilast?

Apremilast is an FDA-approved medication for psoriasis and psoriatic arthritis. It is an inhibitor of phosphodiesterase-4 (PDE4), an enzyme found in immune cells that plays a role in the inflammatory process. By blocking PDE4, apremilast helps to reduce the production of inflammatory mediators and increase anti-inflammatory mediators, thereby reducing inflammation within the body. This action makes it useful in treating inflammatory conditions.

Beyond its approved uses, apremilast is also being investigated in clinical trials for other conditions. These include plaque psoriasis, alcohol use disorder, atopic dermatitis, vitiligo, oral lichen planus, and hidradenitis suppurativa. The drug has been studied in a total of 137 trials, with the first trial starting in 2007 and the latest projected to conclude in 2026. These studies have involved a total of 45,935 participants. Of these trials, 13 are currently recruiting new participants, while 91 have been completed.

Uses and Conditions Under Study

Apremilast is primarily studied for inflammatory skin and joint conditions. For psoriasis, a chronic immune-mediated inflammatory skin condition causing red, scaly plaques, apremilast has been investigated in 31 trials. Similarly, for psoriatic arthritis, which involves joint inflammation often seen in people with psoriasis, it has been studied in 17 trials. An additional 16 trials specifically focus on plaque psoriasis, a common form of the condition, and 4 trials on arthritis, psoriatic. Apremilast's anti-inflammatory properties are believed to help reduce the symptoms of these conditions.

Beyond psoriasis-related conditions, apremilast is also being explored for other inflammatory and immune-mediated disorders. Atopic dermatitis, a chronic itchy skin condition, is being studied in 4 trials to see if apremilast can reduce inflammation and improve symptoms. For vitiligo, a condition causing loss of skin color, there are 3 trials investigating its potential. Oral lichen planus, an inflammatory condition affecting mucous membranes, is the subject of 2 trials, and hidradenitis suppurativa, a chronic inflammatory skin disease, is being examined in 2 trials. Its anti-inflammatory mechanism may offer benefits across these diverse conditions.

Apremilast is also being investigated for conditions outside of dermatology. For alcohol use disorder, 4 trials are exploring its potential role, possibly due to its effects on inflammatory pathways or other neurological mechanisms. Additionally, 3 trials have involved healthy volunteers, typically to study how the drug is absorbed, distributed, metabolized, and excreted in the body.

Dosing

Apremilast is primarily available in oral forms, including tablets and oral suspensions. Various strengths have been studied in clinical trials, ranging from 10 mg to 75 mg. The most commonly studied and approved dose for adults is 30 mg twice daily (BID), often after a titration period to reach this dose. For example, some studies specify "Oral Apremilast titrated to 30 mg twice daily for 8 weeks." Other investigational doses include 20 mg BID, 40 mg QD (once daily), 60 mg/day, and 75 mg XL QD (extended release once daily).

Apremilast can be taken with or without food, though some studies have specifically investigated its pharmacokinetics when administered in both fasted and fed states. For instance, one study compared "Apremilast 30 mg Tablet - Fasted" with "Apremilast 30 mg Oral Suspension - Fasted" and "Apremilast 30 mg Oral Suspension - Fed." While oral tablets are the most common form, a "Topical Apremilast Nanoformula" has also been explored, where a 0.3% formulation was applied as a thin film twice daily for 12 weeks for conditions like psoriasis.

Side Effects

In clinical trials, the most commonly reported side effect for patients taking Apremilast was diarrhea. Across multiple studies involving over 13,900 patients, 12.5% of those on Apremilast experienced diarrhea, compared to 12.0% of patients on placebo. Other frequent side effects included:

• Nasopharyngitis (common cold symptoms): 11.3% of patients on Apremilast experienced this, compared to 6.5% on placebo.
• Nausea: 10.5% on Apremilast vs. 8.8% on placebo.
• Upper respiratory tract infection: 10.3% on Apremilast vs. 6.2% on placebo.
• Headache: 8.8% on Apremilast vs. 8.0% on placebo.
• Bronchitis: 6.2% on Apremilast vs. 1.5% on placebo.
• Vomiting and arthralgia (joint pain): Both occurred in 5.4% of patients on Apremilast, compared to 4.8% and 1.8% respectively on placebo.
• Hypertension (high blood pressure) and sinusitis: Both affected 5.0% of patients on Apremilast, compared to 2.4% and 1.9% respectively on placebo.

Clinical Trial Results

Psoriatic Arthritis

In a Phase II study (NCT00456092) involving adults with psoriatic arthritis, Apremilast demonstrated improvements in disease activity and quality of life. At Week 12, 43.5% of patients taking Apremilast 20 mg twice daily (BID) and 35.8% taking 40 mg once daily (QD) achieved an ACR 20 response (a 20% improvement in disease activity), compared to 11.8% on placebo. For a more significant improvement, an ACR 50 response was achieved by 17.4% (20 mg BID) and 13.4% (40 mg QD) of patients, versus 2.9% on placebo. Similarly, a PsARC (Psoriatic Arthritis Response Criteria) response was seen in 52.2% (20 mg BID) and 50.7% (40 mg QD) of patients, compared to 22.1% on placebo.

Patients also reported improvements in fatigue and quality of life. At Week 12, the mean improvement in the Functional Assessment of Chronic Illness Therapy for Fatigue (FACIT-F) score was 4.1 units for Apremilast 20 mg BID and 4.3 units for 40 mg QD, versus 0.5 units for placebo. The Dermatology Life Quality Index (DLQI) improved by a mean of -1.8 units (20 mg BID) and -2.6 units (40 mg QD), compared to -0.3 units for placebo (lower scores indicate better quality of life). Dactylitis (inflammation of fingers and toes) severity also decreased by a mean of -1.2 units (20 mg BID) and -0.9 units (40 mg QD), versus -0.2 units for placebo.

Plaque Psoriasis

A study (NCT00521339) evaluating Apremilast 20 mg BID in recalcitrant plaque psoriasis showed a mean 59.0% reduction in Psoriasis Area Severity Index (PASI) score at Week 12. At this time point, 46.7% of participants achieved a PASI-50 response (50% improvement), and 30.0% achieved a PASI-75 response. The Dermatology Life Quality Index (DLQI) improved by a mean of -4.7 units. Additionally, 66.7% of participants achieved at least a 1-point reduction in Static Physician Global Assessment (sPGA) score.

Another study (NCT00773734) on moderate-to-severe plaque psoriasis evaluated different doses. At Week 16, 40.9% of patients on Apremilast 30 mg BID achieved a PASI-75 response, compared to 28.7% on 20 mg BID, 11.2% on 10 mg BID, and 5.7% on placebo. At Week 24, 34.1% of patients on Apremilast 30 mg BID achieved an sPGA score of 0 or 1 (clear or almost clear skin), compared to 24.1% on 20 mg BID, 13.5% on 10 mg BID, and 12.6% on placebo. In the long-term extension phase, at 2 years, 50.0% of patients continuously on Apremilast 30 mg BID achieved a PASI-75 response, while 30.0% on 20 mg BID and 20.0% on 10 mg BID also reached this milestone. For patients who initially received placebo and then switched to Apremilast 30 mg BID, 25.0% achieved a PASI-75 response at 2 years.

Behçet Disease

A study (NCT00866359) in Behçet disease showed that Apremilast 30 mg BID significantly reduced oral ulcers. At Day 85, the mean number of oral ulcers was 0.4 for patients on Apremilast, compared to 2.0 for those on placebo. Apremilast also reduced the pain associated with oral ulcers, with a mean Visual Analog Scale (VAS) score of 9.9 units at Day 85, versus 36.7 units for placebo (lower scores indicate less pain). Furthermore, 100% of patients on Apremilast were free of genital ulcers at Day 85, compared to 50% on placebo.

Atopic or Contact Dermatitis

In a study (NCT00931242) for atopic or contact dermatitis, limited data showed that 2 participants achieved a 50% reduction in Eczema Area and Severity Index (EASI) score by Week 12, and 1 participant achieved a 75% reduction. Additionally, 2 participants showed an improvement of two or more points on the Investigator Global Assessment (IGA) scale.

Currently Recruiting Trials

• Yale University is sponsoring a Phase 2 study, NCT07029529, for women and men with Alcohol Use Disorder. This trial plans to enroll 80 participants to evaluate Apremilast 60mg/day against a placebo.

• The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is conducting a Phase 2 human laboratory study, NCT07325266, for Alcohol Use Disorder and Alcohol Misuse. This study aims to enroll 100 individuals to compare the efficacy of two different maintenance doses, Apremilast 60 mg/day and 90 mg/day, in reducing alcohol craving.

• An Early Phase 1 study, NCT07337434, sponsored by Syeda Sana Zaman, is comparing Apremilast and Methotrexate efficacy in patients with moderate to severe Chronic Plaque Psoriasis. The study intends to recruit 106 participants.

• Dow University of Health Sciences is running a Phase 4 study, NCT06593197, on the efficacy and safety of Apremilast in combination with NBUVB (phototherapy) versus NBUVB alone for Vitiligo patients. This trial seeks 30 participants.

• The Centre Hospitalier Universitaire de Nice is sponsoring a Phase 2 study, NCT06509984, assessing the efficacy of Apremilast in 20 patients over 6 years of age with Epidermolysis Bullosa Simplex. This 20-week study will describe the treatment's effectiveness and safety.

• Bristol-Myers Squibb is conducting an observational, real-world study, NCT06382987, in Japan to compare the effectiveness of Deucravacitinib and Apremilast in adults with Plaque Psoriasis. This study aims to enroll 600 participants.

• The National Institute of Mental Health (NIMH) is sponsoring a Phase 1 study, NCT05703685, using PET imaging to study PDE4B in Major Depressive Disorder. This trial plans to enroll 108 participants.

• Amgen is conducting a Phase 3 study, NCT05767047, evaluating the long-term safety of Apremilast in 48 children with oral ulcers associated with Behçet's Disease or Juvenile Psoriatic Arthritis.

• Another real-world observational study, NCT05744466, sponsored by Bristol-Myers Squibb, is comparing the effectiveness of Deucravacitinib versus Apremilast in 1500 adults with Plaque Psoriasis.

• The University Hospital, Rouen, is sponsoring a Phase 3 randomized, double-blind controlled trial, NCT04227314, comparing Apremilast versus placebo in severe forms of Recurrent Aphthous Stomatitis. This study aims to enroll 134 participants.

• Amgen is also sponsoring a Phase 3 pediatric study, NCT04804553, in 60 children aged 5 to less than 18 years with Active Juvenile Psoriatic Arthritis to estimate the efficacy of Apremilast compared to placebo.

• A separate Phase 3 pediatric study, NCT04528082, also sponsored by Amgen, is estimating the efficacy of Apremilast compared to placebo in 60 pediatric participants aged 2 to less than 18 years with oral ulcers associated with Behçet's Disease.

• UMC Utrecht is sponsoring a large Phase 3 adaptive platform trial, NCT02735707, for Community-acquired Pneumonia, Influenza, and COVID-19. This extensive study plans to enroll 20,000 participants to evaluate various interventions, including immune modulation approaches.

Where to Participate

• Los Angeles, California
• Aurora, Colorado
• New Haven, Connecticut
• Jacksonville, Florida
• Augusta, Georgia
• Chicago, Illinois
• New Orleans, Louisiana
• Bethesda, Maryland
• Waltham, Massachusetts
• Ann Arbor, Michigan

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