Biologic Medications for Skin Inflammation

Overseen By Andressa Akabane, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: John Harris

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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to answer: how do inflammation and anti-inflammatory skin therapies work in the skin? Inflammation is a protective response from the body's immune system to injury, disease, or irritation. It is a process by which your body's white blood cells and the things they make protect you from infection from outside invaders such as bacteria and viruses.

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.

What data supports the effectiveness of the drugs used in the clinical trial for skin inflammation?

Research shows that adalimumab and etanercept, which are part of the trial, have been effective in treating psoriasis and rheumatoid arthritis by reducing disease activity and improving quality of life. Etanercept has shown rapid and significant improvement in psoriatic symptoms, and adalimumab has demonstrated superior efficacy over conventional treatments in psoriasis. ^{1 2 3 4 5}

Is adalimumab safe for human use?

Adalimumab, including its biosimilar versions like CinnoRA®, has been shown to be safe and well-tolerated in healthy volunteers, with no significant differences in safety compared to the original product, Humira®. Common side effects reported for anti-TNF drugs like adalimumab include rash, headache, and infections, but no causal associations with serious adverse reactions have been established. ^{6 7 8 9 10}

How is the drug Adalimumab different from other treatments for skin inflammation?

Adalimumab is a biologic medication that works by targeting and blocking a specific protein called TNF alpha, which plays a key role in causing inflammation. This makes it different from traditional treatments that may not specifically target this protein, offering a more focused approach to reducing inflammation in conditions like psoriasis. ^{2 9 11 12 13}

Research Team

John E Harris, MD PhD

Principal Investigator

University of Massachusetts Chan Medical School

Eligibility Criteria

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 am over 18 and do not have any skin diseases.

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

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

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

Treatment Details

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.

Participant Groups

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?

John Harris

Lead Sponsor

Trials

2

Recruited

60+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2015]

2. Croatia pubmed.ncbi.nlm.nih.gov

Biosimilars: An Update on Clinical Trials (Review of Published and Ongoing Studies). [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

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

4. United States 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. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Adalimumab, etanercept, and infliximab utilization patterns and drug costs among rheumatoid arthritis patients. [2015]

6. England 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. [2020]

7. England 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. [2022]

8. England 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). [2022]

9. France pubmed.ncbi.nlm.nih.gov

[Etanercept]. [2019]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Characteristic analysis of adverse reactions of five anti-TNFɑ agents: a descriptive analysis from WHO-VigiAccess. [2023]

11. Germany pubmed.ncbi.nlm.nih.gov

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

12. Australia pubmed.ncbi.nlm.nih.gov

Combination treatment with monoclonal antibodies: Secukinumab, benralizumab and dupilumab for the combined management of psoriasis and severe asthma. [2022]

13. Germany 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. [2021]