AnakinraPhase 1NCT01122914
A Pilot Study Using Anakinra/Kineret for the Treatment of Patients With Severe Atopic Dermatitis
A Phase 1 study testing Anakinra in people with Anakinra and Kineret, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: Severe atopic dermatitis, also known as eczema, is a chronic inflammatory skin condition that affects both children and adults and causes severe itching and skin redness. Current treatments of atopic dermatitis include topical creams and lotions, light therapy, and medications. Read more about this study
- Who is it for?
- Ages 10 to 30 years
- Conditions the study is for
- Anakinra, Kineret, Atopic Dermatitis
- What is being tested?
- Anakinra
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Apr 2010to 7 Apr 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- To be eligible for enrollment in this protocol, participants must fulfill all of the following criteria:
- Must be 10 years to 30 years of age
- Patient or legal guardian must be able to give informed consent
- Must have evidence of severe atopic dermatitis as determined by the investigators and a SCORAD score >40 performed within 90 days of study entry
- Must have report from primary physician documenting lack of sufficient response to topical corticosteroids for > 6 months
- Must have skin test or radioallergosorbent test (RAST) showing sensitivity to greater than or equal to 3 food and/or airborne allergens
Show all 20Show fewer
- Must have a baseline CBC that demonstrates:
- White Blood Cell Count (WBC) greater than or equal to lower limit of normal for age
- Absolute Neutrophil Count (ANC) greater than or equal to lower limit of normal for age
- Platelet Count greater than or equal to lower limit of normal for age
- Must not be pregnant or breastfeeding
- If subject is a female that has begun menstruation, and is sexually active, she must agree to consistently use contraception throughout study participation. Acceptable forms of contraception are:
- Condoms, male or female, with spermicide
- Diaphragm or cervical cap with spermicide
- Intrauterine device
- Contraceptive pills or patch, Norplant, Depo-Provera or other FDA-approved contraceptive method
- Male partner has previously undergone a vasectomy for which there is documentation of aspermatogenic sterility
- Abstinence
- Must have a primary care physician
- Must be willing to submit blood and skin tissue for storage
Who cannot join
- A patient will be ineligible to participate in this protocol if any of the following criteria are fulfilled:
- Patient is taking oral or injectable immunomodulators (such as methotrexate, imuran, and cyclosporine) or biologics (such as etanercept or omalizumab).
- Patient requires systemic immunosuppression at any time during the study
- Patient has known diseases of immunodysregulation or immunodeficiency.
- Any chronic medical condition other than atopic dermatitis, allergy/asthma and infection, such as heart disease, diabetes and autoimmunity that, in the investigator s opinion, places the patient at undue risk by participating in the study.
- History of anaphylactic reaction or hypersensitivity to anakinra.
Show all 12Show fewer
- The presence of certain types of acquired abnormalities of immunity such as human immunodeficiency virus (HIV), cytotoxic chemotherapy for malignancy could be grounds for possible exclusion if, in the opinion of the investigator, the presence of such disease process interferes with evaluating a coexisting abnormality of immunity that is a subject of study under this protocol.
- The presence of any dermatologic diagnosis which, in the investigator's opinion, is not consistent with atopic dermatitis and would impair the ability to assess drug response.
- Has a diagnosis of active tuberculosis with consistent findings from a PPD skin test, computerized tomography (CT) scan or Chest x-ray. Those subjects found to have a positive PPD will be referred back to their primary care physician for appropriate management.
- Has received a live vaccine within 4 weeks prior to therapy or potential need for a live vaccine during the study.
- Is unwilling to undergo testing or procedures associated with this protocol.
- The patient or guardian is unable or unwilling to give daily injections.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Background:
- Severe atopic dermatitis, also known as eczema, is a chronic inflammatory skin condition that affects both children and adults and causes severe itching and skin redness. Current treatments of atopic dermatitis include topical creams and lotions, light therapy, and medications. However, the difficulty with long-term treatment for the chronic and severe nature of the disease requires more effective and better-tolerated therapeutic options.
- Anakinra is a drug that blocks a substance called interleukin-1 (IL-1), which may be important in causing the inflammation in atopic dermatitis. Researchers are interested in determining whether anakinra can be used to help treat atopic dermatitis. Anakinra has been approved by the Food and Drug Administration to treat rheumatoid arthritis in adults and children, but it has not been approved for use in adults or children with atopic dermatitis and is considered an experimental treatment in this study. In this study Anakinra will be administered as an injection under the skin every day for 3 months
Read more
Objectives:
- To assess the safety and effectiveness of using anakinra to treat severe atopic dermatitis in children.
Eligibility:
- Children between 10 and 18 years of age who have been diagnosed with severe atopic dermatitis that has not responded to standard treatment.
Design:
- Initial Screening: Participants will have an initial screening visit with a complete physical examination and medical history, blood and urine tests, photographs of the skin ,skin biopsy, and other tests as required.
- Run-in Period: At the screening visit, participants will receive a diary card and will be asked to track their atopic dermatitis symptoms on standard treatment for 2 months.
- Start of Treatment: At the end of the 2 month Run-in period participants will return for an inpatient visit (2 days) to receive the initial dose of anakinra and will be watched for any side effects. During the inpatient visit, participants will have additional examinations and blood and urine tests, and will be instructed on how to administer the anakinra injections at home.
Treatment Period: - Participants will return once a week for the first 2 weeks of treatment, at the end of the first month, and then once a month for the following 2 months, for a physical exam and blood tests. Participants will be asked to record symptoms related to their atopic dermatitis, anakinra administration and any side effects related to the anakinra on the diary card. The diary cards will be reviewed and collected at each visit.-
End of Treatment Period: At the end of 3 months of treatment with anakinra, participants will again be asked to record symptoms related to their atopic dermatitis on the diary card. Participants will be seen once a month for 3 months for a physical exam, blood tests and review of the diary card. . The final study visit will take place at the end of the 3rd month and will include a physical exam, blood tests, photographs and skin biopsy.
Read the detailed description
Severe refractory atopic dermatitis is a chronic inflammatory pruritic skin condition that affects both children and adults. The disease is marked by periods of exacerbation and remission. Symptoms of atopic dermatitis may resolve by adolescence; however, it is estimated that the disease may persist in 50 percent of affected children well into adulthood.
Current possible treatments of atopic dermatitis include the use of topical corticosteroids, calcineurin inhibitors, phototherapy, as well as systemic medications i.e., methotrexate, cyclosporine, azathioprine, mycophenolate mofetil and interferon gamma. The difficulty with long-term treatment of this disease lies in its chronic nature associated with severe episodes. The combination of chronicity and severity of episodes of this diseases demands more effective and better-tolerated therapeutic options than those that are currently available. While the pathways of allergic inflammation are different than those of other inflammatory conditions, certain elements may overlap, providing targets for immune modulation. One of these targets is the interleukin-1 (IL-1) receptor.
The IL-1 receptor plays an important role in the development and maintenance of Th2 responses. Genetic, in vivo and in vitro data demonstrate a significant role for IL-1 signaling allergic and skin inflammatory conditions. This pilot study is therefore designed to assess the safety and efficacy of IL-1ra, a natural inhibitor of the IL-1 receptor, in disrupting atopic pathophysiologic pathways. Specifically, we will treat severe refractory atopic dermatitis associated with evidence of multiple specific allergic sensitivities. Up to 8 patients ages 10-30 with severe refractory dermatitis will be enrolled. Patients will be initially evaluated to establish the diagnosis of severe refractory AD as evidenced by SCORAD score greater than 40, followed by a 2 month (8 week) run-in period, a 3 month (12 week) treatment period of 3mg/kg/day anakinra given subcutaneously, followed by a 3 month (12 week) post-treatment evaluation period. In order to be considered evaluable for response, patients must have received a minimum of 67 out of 84 doses (80 percent) of anakinra. The primary endpoint is lack of an increase in serious infections, the secondary endpoint is a reduction of 30 percent or more in SCORAD score, and tertiary endpoints are cellular phenotypic and cytokine responses to IL-1 receptor blockade in atopic patients.
- Conditions
- Anakinra, Kineret, Atopic Dermatitis, Eczema, Allergic Disease
- Being tested
- Anakinra
- Keywords
- Kineret, Anakinra, Atopic Dermatitis, Eczema, Allergic Disease
- Medical subject headings
- Dermatitis, Atopic, Eczema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnakinraDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement of Atopic Dermatitis symptoms without increase in serious infections; Response to treatment with a 30 percent decrease in SCORAD score.
Measured: 2 years
Secondary outcomes (1)
Determine immunological phenotype and cytokine profile of peripheral blood before and after treatment with Anakinra; Determine impact of IL-1 r neutralization on total and antigen specific allergen sensitivity.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2010 (estimated)
- Study start14 Apr 2010
- Primary completion7 Apr 2015
- Study completion7 Apr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for AnakinraStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Joshua D Milner, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01122914
- Sponsor's protocol ID
- 100100
- Other IDs
- 10-I-0100
- Status last verified
- 7 Apr 2015
- First submitted
- 11 May 2010
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J Clin Invest. 2004 Mar;113(5):651-7. doi: 10.1172/JCI21060.
PubMed 14991059Adjers K, Pessi T, Karjalainen J, Huhtala H, Hurme M. Epistatic effect of IL1A and IL4RA genes on the risk of atopy. J Allergy Clin Immunol. 2004 Mar;113(3):445-7. doi: 10.1016/j.jaci.2003.12.582.
PubMed 15007345Schmitt J, Schakel K, Schmitt N, Meurer M. Systemic treatment of severe atopic eczema: a systematic review. Acta Derm Venereol. 2007;87(2):100-11. doi: 10.2340/00015555-0207.
PubMed 17340015
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study Using Anakinra/Kineret for the Treatment of Patients With Severe Atopic Dermatitis
- ClinicalTrials.gov ID
- NCT01122914
- Acronym / sponsor ID
- 100100
- Conditions
- Anakinra, Kineret, Atopic Dermatitis, Eczema, Allergic Disease
- Keywords
- Kineret, Anakinra, Atopic Dermatitis, Eczema, Allergic Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 1 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 14 Apr 2010
- Primary completion
- 7 Apr 2015 (actual)
- Study completion
- 7 Apr 2015 (actual)
- First posted
- 13 May 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Severe atopic dermatitis, also known as eczema, is a chronic inflammatory skin condition that affects both children and adults and causes severe itching and skin redness. Current treatments of atopic dermatitis include topical creams and lotions, light therapy, and medications. However, the difficulty with long-term treatment for the chronic and severe nature of the disease requires more effective and better-tolerated therapeutic options.
- Anakinra is a drug that blocks a substance called interleukin-1 (IL-1), which may be important in causing the inflammation in atopic dermatitis. Researchers are interested in determining whether anakinra can be used to help treat atopic dermatitis. Anakinra has been approved by the Food and Drug Administration to treat rheumatoid arthritis in adults and children, but it has not been approved for use in adults or children with atopic dermatitis and is considered an experimental treatment in this study. In this study Anakinra will be administered as an injection under the skin every day for 3 months
Objectives:
- To assess the safety and effectiveness of using anakinra to treat severe atopic dermatitis in children.
Eligibility:
- Children between 10 and 18 years of age who have been diagnosed with severe atopic dermatitis that has not responded to standard treatment.
Design:
- Initial Screening: Participants will have an initial screening visit with a complete physical examination and medical history, blood and urine tests, photographs of the skin ,skin biopsy, and other tests as required.
- Run-in Period: At the screening visit, participants will receive a diary card and will be asked to track their atopic dermatitis symptoms on standard treatment for 2 months.
- Start of Treatment: At the end of the 2 month Run-in period participants will return for an inpatient visit (2 days) to receive the initial dose of anakinra and will be watched for any side effects. During the inpatient visit, participants will have additional examinations and blood and urine tests, and will be instructed on how to administer the anakinra injections at home.
Treatment Period: - Participants will return once a week for the first 2 weeks of treatment, at the end of the first month, and then once a month for the following 2 months, for a physical exam and blood tests. Participants will be asked to record symptoms related to their atopic dermatitis, anakinra administration and any side effects related to the anakinra on the diary card. The diary cards will be reviewed and collected at each visit.-
End of Treatment Period: At the end of 3 months of treatment with anakinra, participants will again be asked to record symptoms related to their atopic dermatitis on the diary card. Participants will be seen once a month for 3 months for a physical exam, blood tests and review of the diary card. . The final study visit will take place at the end of the 3rd month and will include a physical exam, blood tests, photographs and skin biopsy.
Detailed description
Severe refractory atopic dermatitis is a chronic inflammatory pruritic skin condition that affects both children and adults. The disease is marked by periods of exacerbation and remission. Symptoms of atopic dermatitis may resolve by adolescence; however, it is estimated that the disease may persist in 50 percent of affected children well into adulthood.
Current possible treatments of atopic dermatitis include the use of topical corticosteroids, calcineurin inhibitors, phototherapy, as well as systemic medications i.e., methotrexate, cyclosporine, azathioprine, mycophenolate mofetil and interferon gamma. The difficulty with long-term treatment of this disease lies in its chronic nature associated with severe episodes. The combination of chronicity and severity of episodes of this diseases demands more effective and better-tolerated therapeutic options than those that are currently available. While the pathways of allergic inflammation are different than those of other inflammatory conditions, certain elements may overlap, providing targets for immune modulation. One of these targets is the interleukin-1 (IL-1) receptor.
The IL-1 receptor plays an important role in the development and maintenance of Th2 responses. Genetic, in vivo and in vitro data demonstrate a significant role for IL-1 signaling allergic and skin inflammatory conditions. This pilot study is therefore designed to assess the safety and efficacy of IL-1ra, a natural inhibitor of the IL-1 receptor, in disrupting atopic pathophysiologic pathways. Specifically, we will treat severe refractory atopic dermatitis associated with evidence of multiple specific allergic sensitivities. Up to 8 patients ages 10-30 with severe refractory dermatitis will be enrolled. Patients will be initially evaluated to establish the diagnosis of severe refractory AD as evidenced by SCORAD score greater than 40, followed by a 2 month (8 week) run-in period, a 3 month (12 week) treatment period of 3mg/kg/day anakinra given subcutaneously, followed by a 3 month (12 week) post-treatment evaluation period. In order to be considered evaluable for response, patients must have received a minimum of 67 out of 84 doses (80 percent) of anakinra. The primary endpoint is lack of an increase in serious infections, the secondary endpoint is a reduction of 30 percent or more in SCORAD score, and tertiary endpoints are cellular phenotypic and cytokine responses to IL-1 receptor blockade in atopic patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 10 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (20 listed)
- To be eligible for enrollment in this protocol, participants must fulfill all of the following criteria:
- Must be 10 years to 30 years of age
- Patient or legal guardian must be able to give informed consent
- Must have evidence of severe atopic dermatitis as determined by the investigators and a SCORAD score >40 performed within 90 days of study entry
- Must have report from primary physician documenting lack of sufficient response to topical corticosteroids for > 6 months
Key exclusion criteria (12 listed)
- A patient will be ineligible to participate in this protocol if any of the following criteria are fulfilled:
- Patient is taking oral or injectable immunomodulators (such as methotrexate, imuran, and cyclosporine) or biologics (such as etanercept or omalizumab).
- Patient requires systemic immunosuppression at any time during the study
- Patient has known diseases of immunodysregulation or immunodeficiency.
- Any chronic medical condition other than atopic dermatitis, allergy/asthma and infection, such as heart disease, diabetes and autoimmunity that, in the investigator s opinion, places the patient at undue risk by participating in the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anakinra | Drug | – |
Primary outcome
Improvement of Atopic Dermatitis symptoms without increase in serious infections; Response to treatment with a 30 percent decrease in SCORAD score.
Time frame: 2 years
1 secondary outcome
Determine immunological phenotype and cytokine profile of peripheral blood before and after treatment with Anakinra; Determine impact of IL-1 r neutralization on total and antigen specific allergen sensitivity.
Time frame: 2 years
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Background: PubMed 14991059Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J Clin Invest. 2004 Mar;113(5):651-7. doi: 10.1172/JCI21060.
- Background: PubMed 15007345Adjers K, Pessi T, Karjalainen J, Huhtala H, Hurme M. Epistatic effect of IL1A and IL4RA genes on the risk of atopy. J Allergy Clin Immunol. 2004 Mar;113(3):445-7. doi: 10.1016/j.jaci.2003.12.582.
- Background: PubMed 17340015Schmitt J, Schakel K, Schmitt N, Meurer M. Systemic treatment of severe atopic eczema: a systematic review. Acta Derm Venereol. 2007;87(2):100-11. doi: 10.2340/00015555-0207.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joshua D Milner, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Anakinra in people with Anakinra and Kineret, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement of Atopic Dermatitis symptoms without increase in serious infections; Response to treatment with a 30 percent decrease in SCORAD score. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01122914, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2019.