NCT01794117

Anakinra for Inflammatory Pustular Skin Diseases

Completed Phase 2 Results posted Last updated 30 April 2021

What this trial tests

Phase 2 trial testing Anakinra in Sneddon-Wilkinson in 18 participants. Completed in 7 October 2019.

Timeline

22 July 2013

Primary endpoint
19 March 2019

7 October 2019

Quick facts

Lead sponsor	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	18
Start date	22 July 2013
Primary completion	19 March 2019
Estimated completion	7 October 2019
Sites	1 location across United States

Drugs / interventions tested

• Anakinra (ANAKINRA) — full drug profile →

Conditions studied

• Sneddon-Wilkinson — all drugs for Sneddon-Wilkinson →
• Acrodermatitis Continua of Hallopeau — all drugs for Acrodermatitis Continua of Hallopeau →
• Pustular Psoriasis — all drugs for Pustular Psoriasis →
• Palmoplantar Pustulosis — all drugs for Palmoplantar Pustulosis →

Sponsor

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Who can join

Adults 18 to 110, any sex, with Sneddon-Wilkinson or Acrodermatitis Continua of Hallopeau. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Treated With Anakinra Who Achieve 50% Disease Improvement by the End of Week 12, as Measured by Total Body Surface Area Involvement (TBSAI50) Primary · 12 Weeks

Total Body Surface Area Involvement (TBSAI) is defined as the amount of total amount of active disease involvement on a given patient. 50% improvement was the amount of change that we judged at the start of the study would qualify as significant improvement.

Group	Value	95% CI
All Participants	7

Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) Secondary · Up to 16 weeks for participants who completed active treatment (12 weeks) and 4 weeks of follow-up.

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one

Group	Value	95% CI
Week 4 Level 1 Only	1
Week 4 Level 1 Followed by Week 8 Level 2	3
Week 4 Level 1, Followed by Week 8 Level 2, Followed by Week 12 Level 2	2
Week 4 Level 1, Followed by Week 8 Level 2, Followed by Week 12 Level 3	12

Average Change in Total Body Surface Area Index (TBSAI) Secondary · Baseline and 12 Weeks

Median difference in affected area of plaque and pustular disease between baseline and week 12.

Group	Value	95% CI
All Participants	-0.9	-1.8 – 0.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 16 weeks for participants who completed active treatment (12 weeks) and 4 weeks of follow-up.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Week 4 Level 1 Only

Serious: 1/1 (100%)

Deaths: 0/1

Week 4 Level 1 Followed by Week 8 Level 2

Serious: 0/3 (0%)

Deaths: 0/3

Week 4 Level 1, Followed by Week 8 Level 2, Followed by Week 12 Level 2

Serious: 0/2 (0%)

Deaths: 0/2

Week 4 Level 1, Followed by Week 8 Level 2, Followed by Week 12 Level 3

Serious: 0/12 (0%)

Deaths: 0/12

Serious adverse events (1 terms)

Reaction	System	Week 4 Level 1 Only	Week 4 Level 1 Followed by…	Week 4 Level 1, Followed b…	Week 4 Level 1, Followed b…
Skin and subcutaneous tissue disorders - Other, Flare of Pustular Psoriasis	Skin and subcutaneous tissue disorders	—	—	—	—

Other adverse events (61 terms — click to expand)

Reaction	System	Week 4 Level 1 Only	Week 4 Level 1 Followed by…	Week 4 Level 1, Followed b…	Week 4 Level 1, Followed b…
Injection site reaction	General disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—	—
Pain	General disorders	—	—	—	—
Fatigue	General disorders	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Creatinine increased	Investigations	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Edema limbs	General disorders	—	—	—	—
Malaise	General disorders	—	—	—	—
Pain of skin	Skin and subcutaneous tissue disorders	—	—	—	—
Upper respiratory infection	Infections and infestations	—	—	—	—
Anemia	Blood and lymphatic system disorders	—	—	—	—
Chills	General disorders	—	—	—	—
Fever	General disorders	—	—	—	—
Hypoalbuminemia	Metabolism and nutrition disorders	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—
Alkaline phosphatase increased	Investigations	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—
Cholesterol high	Investigations	—	—	—	—
GGT increased	Investigations	—	—	—	—
Hypernatremia	Metabolism and nutrition disorders	—	—	—	—
Hyperuricemia	Metabolism and nutrition disorders	—	—	—	—
Hypocalcemia	Metabolism and nutrition disorders	—	—	—	—
Hypokalemia	Metabolism and nutrition disorders	—	—	—	—
Infections and infestations - Other, L foot infection	Infections and infestations	—	—	—	—
Paresthesia	Nervous system disorders	—	—	—	—
Portal vein thrombosis	Hepatobiliary disorders	—	—	—	—
Respiratory, thoracic and mediastinal disorders - Other, Running Nose	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Bruising	Injury, poisoning and procedural complications	—	—	—	—
Eye disorders - Other, (Stye L eye)	Eye disorders	—	—	—	—
Eye disorders - Other, (Stye R eye)	Eye disorders	—	—	—	—
Hyperglycemia	Metabolism and nutrition disorders	—	—	—	—
Lymphocyte count decreased	Investigations	—	—	—	—
Skin infection	Infections and infestations	—	—	—	—
Allergic rhinitis	Respiratory, thoracic and mediastinal disorders	—	—	—	—

Most-reported serious reactions: Skin and subcutaneous tissue disorders - Other, Flare of Pustular Psoriasis.

Data from ClinicalTrials.gov NCT01794117 adverse events section.

Sponsor's own description

Background:

* Inflammatory pustular skin diseases are a type of autoinflammatory disease in which the immune system attacks the bodys tissues. These diseases cause painful and itchy skin rashes, eye and mouth irritation, joint pain and fever. Several drugs for treating these diseases suppress the immune system. However, they can cause severe side effects when taken over a long period of time.
* Interleukin 1 (IL-1) is a small protein that may be important in causing the inflammation seen in pustular skin disease. Anakinra is a drug that works by blocking IL-1. It has been effective in treating some inflammatory conditions such as rheumatoid arthritis. However, anakinra has not been studied for use in patients with pustular skin disease. Researchers want to see whether anakinra will be effective in treating pustular skin disease.

Objectives:

\- To see if anakinra can be used to treat inflammatory pustular skin disease.

Eligibility:

\- Individuals at least 18 years of age who have inflammatory pustular skin disease.

Design:

* Participants will be screened with a physical exam and medical history. Their disease will be evaluated with blood tests, urine tests and imaging studies. Skin biopsies may also be collected.
* Participants will have an initial visit to receive the first dose of anakinra. They will be shown how to give themselves daily injections of anakinra.
* Participants will take anakinra for up to 12 weeks as long as there are no severe side effects. During this time, they will keep a study diary to record the severity of any rashes, pustules, itching, fevers, and skin or joint pain. They will bring this diary to their study visits.
* Participants will have study visits at weeks 4, 8 and 12. Treatment will be monitored at these visits with blood tests, urine tests and physical exams. Depending on the effects of the treatment, participants may have the dose of anakinra increased or decreased.
* Participants will have a final study visit 4 weeks after they stop taking anakinra.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. Palmoplantar Pustulosis: Recent Advances in Etiopathogenesis and Emerging Treatments.
   Misiak-Galazka M, Zozula J, Rudnicka L. · · 2020 · cited 79× · PMID 32008176 · DOI 10.1007/s40257-020-00503-5
2. Biological treatments: new weapons in the management of monogenic autoinflammatory disorders.
   Vitale A, Rigante D, Lucherini OM, Caso F, et al · · 2013 · cited 48× · PMID 23970817 · DOI 10.1155/2013/939847
3. Biologics or tofacitinib for people with rheumatoid arthritis naive to methotrexate: a systematic review and network meta-analysis.
   Singh JA, Hossain A, Mudano AS, Tanjong Ghogomu E, et al · · 2017 · cited 44× · PMID 28481462 · DOI 10.1002/14651858.cd012657
4. Pustular Psoriasis: From Pathophysiology to Treatment.
   Genovese G, Moltrasio C, Cassano N, Maronese CA, et al · · 2021 · cited 40× · PMID 34944562 · DOI 10.3390/biomedicines9121746
5. Biologics or tofacitinib for people with rheumatoid arthritis unsuccessfully treated with biologics: a systematic review and network meta-analysis.
   Singh JA, Hossain A, Tanjong Ghogomu E, Mudano AS, et al · · 2017 · cited 38× · PMID 28282491 · DOI 10.1002/14651858.cd012591
6. Therapeutic Development Based on the Immunopathogenic Mechanisms of Psoriasis.
   Tseng JC, Chang YC, Huang CM, Hsu LC, et al · · 2021 · cited 27× · PMID 34371756 · DOI 10.3390/pharmaceutics13071064