Biologic Medications for Skin Inflammation

Overseen By Isaac (Li-Chi) Chen, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Wei-Che Ko

Must not be taking: Immunosuppressants

Disqualifiers: Psoriasis, Diabetes, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand the mechanisms of inflammation and anti-inflammatory therapies in skin conditions like atopic dermatitis and non-melanoma skin cancer. Researchers are testing several treatments, including biologic medications (drugs made from living organisms) and topical steroids, to assess their effects on skin inflammation. Healthy adults or those with specific skin conditions who have undergone clinical patch testing would be a good fit for this trial. As a Phase 2 and Phase 3 trial, the research measures the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering participants a chance to contribute to significant advancements in skin condition therapies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on systemic broad-spectrum immunosuppression (like prednisone, mycophenolate mofetil, azathioprine, or methotrexate), you cannot participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the treatments in this trial have varying safety levels based on past studies and their use for other health issues.

Dupilumab is generally well-tolerated in long-term studies for conditions like atopic dermatitis, with most side effects being mild to moderate. In contrast, adalimumab can lead to serious infections and allergic reactions, observed in patients with various conditions.

Ustekinumab is usually well-tolerated, but it can cause serious allergic reactions. Similarly, guselkumab has a good long-term safety record, though it may also lead to severe allergic reactions.

Canakinumab can cause mild reactions at the injection site, such as swelling and redness. Sarilumab may cause serious allergic reactions, requiring careful monitoring.

Topical steroids like betamethasone valerate, triamcinolone acetonide, and fluticasone propionate are generally safe for short-term use on the skin, but they can cause skin irritation or a rash from contact.

Overall, while these treatments can have side effects, many are manageable or rare. Participants should discuss any concerns with the trial team to understand the risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for skin inflammation because they offer a variety of innovative approaches to managing allergic contact dermatitis. Unlike the standard topical corticosteroids and systemic immunosuppressants, these treatments include biologics like dupilumab, adalimumab, and ustekinumab that target specific immune pathways, potentially offering more precise control of inflammation with fewer side effects. Additionally, some treatments like canakinumab and guselkumab focus on different cytokines involved in the inflammatory process, which might provide relief for patients who don't respond to traditional therapies. These biologics could redefine treatment by offering faster and more sustained relief, revolutionizing care for those with persistent skin inflammation.

What evidence suggests that this trial's treatments could be effective for skin inflammation?

Research has shown that several treatments hold promise for skin inflammation. In this trial, participants in the "Contact Allergen with Immunomodulator Pre-Treatment" arm may receive one of the following biologics: Dupilumab, which has reduced the severity of atopic dermatitis by 75% or more in many cases; Adalimumab, which has significantly improved skin symptoms in plaque psoriasis; Guselkumab, which has led to completely clear skin in some psoriasis patients within 16 weeks; Canakinumab, which has lowered inflammation markers and reduced symptoms and flare-ups in various conditions; or Sarilumab, which has effectively reduced inflammation in rheumatoid arthritis and may also benefit skin inflammation. Alternatively, participants may receive a single application of one of the following topical steroids: Betamethasone valerate, Triamcinolone acetonide, or Fluticasone propionate, all known to reduce skin inflammation and symptoms in conditions like dermatitis. These treatments target and reduce the immune response that causes inflammation. ^{4 6 7 8 9}

Who Is on the Research Team?

Wei-Che Ko, MD

Principal Investigator

University of Massachusetts Chan Medical School

Are You a Good Fit for This Trial?

This trial is for adults over 18 with skin conditions like eczema or a history of certain non-melanoma skin cancers. UMass Medical School students and employees, including non-English speakers with interpreter support, can join. It's not for pregnant women, those on broad immunosuppressants, with specific skin diseases (like psoriasis), high TB risk, liver disease/alcohol abuse, uncontrolled diabetes, compromised immune systems or poor wound healing.

Inclusion Criteria

You have had patch testing done in a previous clinical trial.

I have skin conditions like eczema or a history of certain skin cancers.

UMass Medical School students and employees are eligible to participate

Exclusion Criteria

I have diabetes that is not well-controlled.

I have a history of wounds healing poorly.

You have a history of skin that tears easily.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Contact Allergen

Allergic contact dermatitis is induced via squaric acid dibutyl ester (SADBE) and/or known patch test allergens followed by skin and blood sampling.

4 weeks

1 visit (in-person)

Contact Allergen with Immunomodulator Pre-Treatment

Participants are pre-treated with a single dose of a biologic or a single application of a topical steroid, followed by induction of allergic contact dermatitis and skin sampling.

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Adalimumab
• Betamethasone Valerate
• Canakinumab
• Dupilumab
• Fluticasone Propionate
• Guselkumab
• Sarilumab
• Triamcinolone Acetonide
• Ustekinumab

Trial Overview The study tests how inflammation and anti-inflammatory treatments work in the skin using biologic medications like Dupilumab and Guselkumab among others. Participants will undergo procedures such as skin punch biopsy and suction blistering to study the effects of these therapies on inflammatory responses.

How Is the Trial Designed?

Group I: Contact Allergen with Immunomodulator Pre-Treatment Experimental Treatment 14 Interventions

Individuals from Arm 1 (Baseline Contact Allergen) who have been exposed to SADBE and/or known patch test allergens followed by skin and blood sampling. These individuals will be pre-treated via administration of a single dose of 1 biologic from the following list: dupilumab, adalimumab, ustekinumab, guselkumab, canakinumab, sarilumab; or a single application of 1 topical steroid from the following list: betamethasone valerate, triamcinolone acetonide, fluticasone propionate. Allergic contact dermatitis will then be induced and the skin sampled.

Group II: Baseline Contact Allergen Experimental Treatment 5 Interventions

Individuals who will have allergic contact dermatitis induced via squaric acid dibutyl ester (SADBE) and/or known patch test allergens followed by skin and blood sampling. There is a protocol to sensitize individuals to SADBE if they have not previously been exposed to SADBE.

Adalimumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

Approved in United States as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis
• Hidradenitis suppurativa

Approved in Canada as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

Approved in Japan as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

Who Is Running the Clinical Trial?

Wei-Che Ko

Lead Sponsor

John Harris

Lead Sponsor

Trials

2

Recruited

60+

Published Research Related to This Trial

Etanercept is an FDA-approved treatment for rheumatoid arthritis and other inflammatory conditions, showing efficacy in patients who do not respond to traditional disease-modifying antirheumatic drugs (DMARDs).

While etanercept has demonstrated positive results in treating various conditions, including psoriasis and juvenile arthritis, concerns remain about its long-term safety and high cost, necessitating careful consideration in its prescription.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Etanercept]. Sparsa, A.[2019]

Biosimilars, such as those for adalimumab, etanercept, and infliximab, show no clinically relevant differences in efficacy and safety compared to their reference medications, based on randomized controlled trials in patients with conditions like ankylosing spondylitis and rheumatoid arthritis.

The primary advantage of biosimilars is their lower cost, which is achieved through specific study designs, but there is a need for more registered clinical trials to provide comprehensive data on their effectiveness and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biosimilars: An Update on Clinical Trials (Review of Published and Ongoing Studies). Olteanu, R., Zota, A., Constantin, M.[2022]

Anti-TNF-alpha agents like etanercept, infliximab, and adalimumab have been shown to significantly reduce disease activity in rheumatoid arthritis (RA), with long-term studies indicating sustained clinical responses for up to 5 years.

Etanercept not only matches the efficacy of methotrexate in early RA but also outperforms it in preventing radiographic progression, suggesting that it may help reduce long-term costs associated with disease outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drugs that block tumour necrosis factor: experience in patients with rheumatoid arthritis. Moreland, LW.[2018]

CinnoRA®, a biosimilar to Humira®, demonstrated pharmacokinetic equivalence in a study of 74 healthy volunteers, showing similar serum concentration profiles for both drugs after a single injection.

The study found that CinnoRA® was safe and well-tolerated, with no significant differences in adverse events compared to Humira®, indicating it could be a viable alternative for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase I pharmacokinetic trial comparing the potential biosimilar adalimumab (CinnoRA®) with the reference product (Humira®) in healthy volunteers. Jamshidi, A., Sabzvari, A., Anjidani, N., et al.[2020]

A total of 1,403,273 adverse events related to five TNF inhibitors were reported, with the most common adverse reactions including infections, musculoskeletal disorders, and gastrointestinal issues, highlighting the need for careful monitoring of patients on these medications.

Infliximab was associated with a higher rate of infusion-related reactions, while golimumab had the highest reports of lower respiratory tract infections, suggesting that different TNF inhibitors may carry unique risks that should be considered when prescribing them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristic analysis of adverse reactions of five anti-TNFɑ agents: a descriptive analysis from WHO-VigiAccess. Li, M., You, R., Su, Y., et al.[2023]

In a study involving 136 adult patients with active rheumatoid arthritis, the test drug CinnoRA® was found to be non-inferior to the innovator product Humira® in achieving moderate and good disease activity responses after 24 weeks of treatment.

Both CinnoRA® and Humira® demonstrated comparable safety profiles, with no significant differences in adverse effects or disability scores, indicating that CinnoRA® is a viable alternative to Humira® for treating rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III, randomized, two-armed, double-blind, parallel, active controlled, and non-inferiority clinical trial to compare efficacy and safety of biosimilar adalimumab (CinnoRA®) to the reference product (Humira®) in patients with active rheumatoid arthritis. Jamshidi, A., Gharibdoost, F., Vojdanian, M., et al.[2022]

Etanercept is an effective treatment for psoriatic arthritis and psoriasis vulgaris, showing significant efficacy in controlled studies for both skin and joint symptoms.

The drug is generally well-tolerated with a good safety profile, but patients must be monitored for infections like tuberculosis before starting therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Etanercept. An effective TNF alpha-antagonist in the treatment of psoriatic arthritis and chronic plaque psoriasis]. Wozel, G.[2018]

In a study involving 466 patients with moderate-to-severe plaque psoriasis, the combination of rhTNFR-Fc and methotrexate (MTX) resulted in a significantly higher rate of improvement (81.86% achieving PASI 75) compared to rhTNFR-Fc plus placebo (65.50%) at week 24.

The combination therapy was found to be effective and well-tolerated, with common side effects including upper respiratory tract infections and abnormal liver function, indicating a favorable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etanercept biosimilar (recombinant human tumor necrosis factor-α receptor II: IgG Fc fusion protein) and methotrexate combination therapy in Chinese patients with moderate-to-severe plaque psoriasis: a multicentre, randomized, double-blind, placebo-controlled trial. Liu, LF., Chen, JS., Gu, J., et al.[2021]

In a 16-week study involving 270 psoriasis patients, adalimumab (ADA) showed a significantly better safety profile compared to methotrexate (MTX) and placebo, with more days free from adverse events (AEs).

ADA treatment resulted in approximately four times as many days of response without any AEs compared to MTX or placebo, indicating a superior benefit-risk profile for patients with psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit-risk analysis of adalimumab versus methotrexate and placebo in the treatment of moderate to severe psoriasis: comparison of adverse event-free response days in the CHAMPION trial. Reich, K., Signorovitch, J., Ramakrishnan, K., et al.[2015]

The study analyzed the use of anti-TNF agents in rheumatoid arthritis patients, revealing that a significant portion of patients had refill patterns that were longer than recommended, leading to potential gaps in therapy.

Cost comparisons showed that while the first-year medication costs varied among the three agents (adalimumab, etanercept, and infliximab), optimal treatment compliance could lead to similar annual costs, highlighting the importance of adherence in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab, etanercept, and infliximab utilization patterns and drug costs among rheumatoid arthritis patients. Carter, CT., Changolkar, AK., Scott McKenzie, R.[2015]

In a study of 157 patients with moderate to severe plaque psoriasis, 55% achieved at least a 50% improvement in their symptoms (PASI 50) after continuing etanercept treatment for 60 weeks, despite not responding adequately at 24 weeks.

Etanercept was found to be safe and well tolerated, showing a similar safety profile for patients who responded quickly and those who initially did not respond well to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients with psoriasis respond to continuous open-label etanercept treatment after initial incomplete response in a randomized, placebo-controlled trial. Krueger, GG., Elewski, B., Papp, K., et al.[2015]

The study demonstrated that AVT02, an adalimumab biosimilar, is bioequivalent to both the EU- and US-approved reference products, with pharmacokinetic parameters falling within the acceptable range of 80% to 125% for bioequivalence.

Safety and immunogenicity profiles of AVT02 were found to be comparable to those of the reference products, indicating that it is a safe alternative for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, adaptive design, double-blind, 3-arm, parallel study assessing the pharmacokinetics and safety of AVT02, a high-concentration (100 mg/mL) Adalimumab biosimilar, in healthy adult subjects (ALVOPAD FIRST). Wynne, C., Schwabe, C., Lemech, C., et al.[2022]

A woman successfully treated for psoriasis and psoriatic arthritis with the IL-17 inhibitor secukinumab also managed her severe asthma and nasal polyps with other biologics, demonstrating the potential for concurrent treatment of multiple inflammatory conditions.

The use of secukinumab alongside IL-5 and IL-4 receptor inhibitors highlights the efficacy of targeted biological therapies in managing complex cases of inflammation, suggesting a promising approach for patients with overlapping inflammatory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination treatment with monoclonal antibodies: Secukinumab, benralizumab and dupilumab for the combined management of psoriasis and severe asthma. Mahar, PD., Zubrinich, CM., Manuelpillai, N., et al.[2022]

Citations

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Long-Term Safety of Adalimumab in 29967 Adult Patients ... Here we report the long-term safety of adalimumab in adults with plaque psoriasis (Ps), hidradenitis suppurativa (HS), rheumatoid arthritis (RA), ankylosing ...

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Outcomes of a Mandatory Switch From Adalimumab to ... In this cohort study from Denmark, a nonmedical switch from adalimumab originator to adalimumab biosimilars was not associated with drug retention.

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AbbVie Announces Pivotal Phase 3 Data Evaluating ... Results from the PIONEER I study show that moderate-to-severe HS patients treated with HUMIRA 40 mg weekly achieved a significantly greater ...

4. ccjm.org ccjm.org/content/87/5/288

Cutaneous adverse effects of biologic medications Injection site reactions have been reported to occur in 6% to 37% of patients receiving adalimumab, 17% to 37% of patients receiving etanercept, ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/cod.13584

Review of biologics in allergic contact dermatitis These newer agents offer major promise in the treatment of contact dermatitis by targeting specific mediators or pathways of inflammation.

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HUMIRA® (adalimumab) Safety profile Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death.

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Adalimumab (subcutaneous route) - Side effects & dosage Adalimumab may cause serious allergic reactions (eg, anaphylaxis and angioneurotic edema), which can be life-threatening and requires immediate ...

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HUMIRA® (adalimumab) - FAQs Warning signs of a serious allergic reaction may include hives, swelling of your face, eyes, lips or mouth or trouble breathing. If you experience any of these ...

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Humira | European Medicines Agency (EMA) Other rare serious side effects (which may affect up to 1 in 1,000 people) include failure of bone marrow to produce blood cells, nerve damage caused by ...