Hidradenitis SuppurativaPhase 2NCT01558375
Anakinra in Hidradenitis Suppurativa
A Phase 2 study testing Water for injection and Anakinra in people with Hidradenitis Suppurativa, run by University of Athens at 2 sites in Greece.
Trial summary
Aim of this double-blind, randomized, controlled clinical trial is to compare the safety and the efficacy of anakinra over placebo for the management of patients with hidradenitis suppurativa (HS) of Hurley II and Hurley III disease stage. Patients will be evaluated on subsequent follow-up visits. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hidradenitis Suppurativa
- What is being tested?
- Water for injection and Anakinra
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 2 sitesGreece
- Study dates
- Mar 2012to Feb 2014
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- written informed consent provided by the patient;
- age above 18 years;
- diagnosis of hidradenitis suppurativa; and
- disease of Hurley II or III severity stage
Who cannot join
- history of systemic lupus erythematosus, of rheumatoid arthritis of of seronegative inflammatory arthritis;
- any prior administration of any type of anti-TNF therapy over the last six months;
- administration of any live (attenuated) vaccine over the last 4 weeks;
- history of recurrent vein thrombosis or embolism compatible with anti-cardiolipin syndrome;
- any present or smoldering infection;
- hepatic dysfunction defined as any value of transaminases, of γ-glutamyl transpeptidase or of bilirubin> 2 x upper normal limit;
Show all 12Show fewer
- history of haematological or solid tumor malignancy, arterial hypertension, liver cirrhosis, HIV infection, and hepatitis virus B or C infection
- history of episodes mimicking demyelinating disorders or a definite diagnosis of multiple sclerosis
- any creatinine value above 1.5 mg/dl
- intake of corticosteroids defined as daily intake of prednisone or equivalent more than 1mg/kg for the last three weeks;
- neutropenia defined as <1000 neutrophils/mm3; and
- pregnancy or lactation
Trial locations and contacts
2 sites in 1 country.
Greece2 sites
2nd Department of Dermatology, ATTIKON University Hospital
Athens, 12462
4th Department of Internal Medicine, ATTIKON University Hospital
Athens, 12462
About this study
Official title: A Double-blind, Randomized, Placebo-controlled Clinical Trial of the Safety and Efficacy of Anakinra in Patients With Hidradenitis Suppurativa
Aim of this double-blind, randomized, controlled clinical trial is to compare the safety and the efficacy of anakinra over placebo for the management of patients with hidradenitis suppurativa (HS) of Hurley II and Hurley III disease stage. Patients will be evaluated on subsequent follow-up visits. Two scores will be applied: disease activity as assessed in the protocol by the investigator; and Sartorius score. Primary efficacy endpoint will be the comparisons of visual analogue scores, of disease activity, of Sartorius score and of dermatology life quality index between the two groups of treatment over follow-up.
Read the detailed description
Hidradenitis suppurativa (HS) is a chronic devastating skin disorder affecting areas rich in apocrine glands. Nodules appear in the affected areas; they progressively become swollen and rupture with the release of pus. This process occurs repeatedly leading to sinus tract formation and scars. This disease course creates a frustrating situation for the patients but also for physicians. Traditional treatments comprise short-courses of antibiotics and surgical excision. However, relapse is the rule so that HS leads to severe impairment of the quality of life. The Dermatology Quality Life Index (DQLI) for HS is 8.9 being higher than any other skin disorder.
This devastating disorder has often been neglected and considered a rare situation. However, HS seems to indiscriminately affect the global population. Although the exact epidemiology is largely unknown, the point-prevalence is reported to range between 1% and 4%. A recent large epidemiological survey in France reports 0.97% disease prevalence.
The exact pathophysiology of HS is unknown. Smoking, dietary habits and genetic predisposition have all been linked with HS. However, a recent survey by our group in 56 patients, disclosed a severe derangement of the monocyte function and of subsequent antigen processing in these patients. The percentage of natural killer (NK) cells was increased and that of CD4-lymphocytes decreased compared to healthy controls probably implying the existence of an autoimmune predilection for the disorder. We have previously demonstrated defective lipopolysaccharide (LPS)-induced production of the pro-inflammatory cytokines, tumour necrosis factor(TNF) and interleukin (IL)-6 by blood monocytes of patients with HS.
As a consequence, a hypothesis for the implication of some autoimmune of autoinflammatory mechanism in the pathogenesis of HS was started to be created over the last years. The hypothesis is further reinforced by positive results from the administration of TNF antagonists in prospective studies with limited number of patients one of these was conducted by our study group. Subcutaneous treatment with 50mg etanercept once weekly for 12 weeks in 10 patients, reduced patients' suffering, attenuated local signs of inflammation and retarded disease relapse.
Anakinra is a recombinant interleukin-1 (IL-1) receptor antagonist (IL-1Ra). Anakinra blocks the biologic activity of naturally occurring IL-1, including inflammation and cartilage degradation associated with rheumatoid arthritis, by competitively inhibiting the binding of IL-1 to the interleukin-1 type receptor, which is expressed in many tissues and organs. IL-1 is produced in response to inflammatory stimuli and mediates various physiologic responses, including inflammatory and immunologic reactions. The biological properties of anakinra and the existing clinical and laboratory data favoring a derangement of the immune response in HS, prompted to investigate whether anakinra would be efficient in the management of patients with HS.
- Conditions
- Hidradenitis Suppurativa
- Being tested
- Water for injection, Anakinra
- Medical subject headings
- Hidradenitis Suppurativa
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Water for injectionDrug
Also called Sterile water
Placebo syringes will contain 0.67ml of sterile water for injection. This will be injecteda daily for 12 weeks.
AnakinraDrug
Also called Recombinant human IL-1 receptor antagonist
Anakinra will be supplied in single use pre-filed glass syringes with 27-gauge needles. Anakinra syringe will contain 100mg of anakinra at a volume of 0.67 ml. This will be injected subcutaneously daily for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Water for injection | Placebo comparator | Placebo syringes will contain 0.67ml of sterile water for injection. This will be injected daily for 12 weeks. Receives: Drug: Water for injection |
| Anakinra | Experimental | Anakinra will be supplied in single use pre-filed glass syringes with 27-gauge needles. Anakinra syringe will contain 100mg of anakinra at a volume of 0.67 ml. This will be injected subcutaneously daily for 12 weeks. Receives: Drug: Anakinra |
What is being measured
The primary outcome is the main question the study is designed to answer.
The efficacy of anakinra in patients with HS of Hurley II and III stage disease.
This will be defined by the changes of scoring parameters between the two study groups over visits.
Measured: 24 weeks
Secondary outcomes (3)
The effect of anakinra in the ex vivo function of monocytes of patients with HS.
This will be defined by the differences of cytokines produced by PBMCs between the two study groups over visits.
Measured: 24 weeks
The effect of anakinra on the time to new exacerbation
This will be defined by the differences between the two study groups over visits.
Measured: 24 weeks
The safety of anakinra in patients with hidradenitis suppurativa
This will be assessed by the development of serious and non-serious drug-related adverse events
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2012 (estimated)
- Study startMar 2012
- Primary completionFeb 2014
- Study completionFeb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Hidradenitis SuppurativaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Athens
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Evangelos J. Giamarellos-Bourboulis, M.D., University of Athens
- Investigators
- Evangelos J Giamarellos-Bourboulis, MD, PhD, Study chair, University of Athens, Medical School, GreeceDimitrios Rigopoulos, MD, PhD, Principal investigator, University of Athens, Medical School, Greece
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01558375
- Sponsor's protocol ID
- HIDRA03
- Status last verified
- May 2015
- First submitted
- 15 Mar 2012
- Last updated
- 27 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Giamarellos-Bourboulis EJ, Pelekanou E, Antonopoulou A, Petropoulou H, Baziaka F, Karagianni V, Stavrianeas N, Giamarellou H. An open-label phase II study of the safety and efficacy of etanercept for the therapy of hidradenitis suppurativa. Br J Dermatol. 2008 Mar;158(3):567-72. doi: 10.1111/j.1365-2133.2007.08372.x. Epub 2007 Dec 11.
PubMed 18076705Giamarellos-Bourboulis EJ, Antonopoulou A, Petropoulou C, Mouktaroudi M, Spyridaki E, Baziaka F, Pelekanou A, Giamarellou H, Stavrianeas NG. Altered innate and adaptive immune responses in patients with hidradenitis suppurativa. Br J Dermatol. 2007 Jan;156(1):51-6. doi: 10.1111/j.1365-2133.2006.07556.x.
PubMed 17199566Kurzen H, Kurokawa I, Jemec GB, Emtestam L, Sellheyer K, Giamarellos-Bourboulis EJ, Nagy I, Bechara FG, Sartorius K, Lapins J, Krahl D, Altmeyer P, Revuz J, Zouboulis CC. What causes hidradenitis suppurativa? Exp Dermatol. 2008 May;17(5):455-6; discussion 457-72. doi: 10.1111/j.1600-0625.2008.00712_1.x.
PubMed 18400064Pelekanou A, Kanni T, Savva A, Mouktaroudi M, Raftogiannis M, Kotsaki A, Giamarellos-Bourboulis EJ. Long-term efficacy of etanercept in hidradenitis suppurativa: results from an open-label phase II prospective trial. Exp Dermatol. 2010 Jun;19(6):538-40. doi: 10.1111/j.1600-0625.2009.00967.x. Epub 2009 Sep 16.
PubMed 19758320Tzanetakou V, Kanni T, Giatrakou S, Katoulis A, Papadavid E, Netea MG, Dinarello CA, van der Meer JWM, Rigopoulos D, Giamarellos-Bourboulis EJ. Safety and Efficacy of Anakinra in Severe Hidradenitis Suppurativa: A Randomized Clinical Trial. JAMA Dermatol. 2016 Jan;152(1):52-59. doi: 10.1001/jamadermatol.2015.3903.
PubMed 26579854
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomized, Placebo-controlled Clinical Trial of the Safety and Efficacy of Anakinra in Patients With Hidradenitis Suppurativa
- ClinicalTrials.gov ID
- NCT01558375
- Acronym / sponsor ID
- HIDRA03
- Conditions
- Hidradenitis Suppurativa
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of AthensUniversity, hospital or other
- Study start
- Mar 2012
- Primary completion
- Feb 2014 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 20 Mar 2012 (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.
Aim of this double-blind, randomized, controlled clinical trial is to compare the safety and the efficacy of anakinra over placebo for the management of patients with hidradenitis suppurativa (HS) of Hurley II and Hurley III disease stage. Patients will be evaluated on subsequent follow-up visits. Two scores will be applied: disease activity as assessed in the protocol by the investigator; and Sartorius score. Primary efficacy endpoint will be the comparisons of visual analogue scores, of disease activity, of Sartorius score and of dermatology life quality index between the two groups of treatment over follow-up.
Detailed description
Hidradenitis suppurativa (HS) is a chronic devastating skin disorder affecting areas rich in apocrine glands. Nodules appear in the affected areas; they progressively become swollen and rupture with the release of pus. This process occurs repeatedly leading to sinus tract formation and scars. This disease course creates a frustrating situation for the patients but also for physicians. Traditional treatments comprise short-courses of antibiotics and surgical excision. However, relapse is the rule so that HS leads to severe impairment of the quality of life. The Dermatology Quality Life Index (DQLI) for HS is 8.9 being higher than any other skin disorder.
This devastating disorder has often been neglected and considered a rare situation. However, HS seems to indiscriminately affect the global population. Although the exact epidemiology is largely unknown, the point-prevalence is reported to range between 1% and 4%. A recent large epidemiological survey in France reports 0.97% disease prevalence.
The exact pathophysiology of HS is unknown. Smoking, dietary habits and genetic predisposition have all been linked with HS. However, a recent survey by our group in 56 patients, disclosed a severe derangement of the monocyte function and of subsequent antigen processing in these patients. The percentage of natural killer (NK) cells was increased and that of CD4-lymphocytes decreased compared to healthy controls probably implying the existence of an autoimmune predilection for the disorder. We have previously demonstrated defective lipopolysaccharide (LPS)-induced production of the pro-inflammatory cytokines, tumour necrosis factor(TNF) and interleukin (IL)-6 by blood monocytes of patients with HS.
As a consequence, a hypothesis for the implication of some autoimmune of autoinflammatory mechanism in the pathogenesis of HS was started to be created over the last years. The hypothesis is further reinforced by positive results from the administration of TNF antagonists in prospective studies with limited number of patients one of these was conducted by our study group. Subcutaneous treatment with 50mg etanercept once weekly for 12 weeks in 10 patients, reduced patients' suffering, attenuated local signs of inflammation and retarded disease relapse.
Anakinra is a recombinant interleukin-1 (IL-1) receptor antagonist (IL-1Ra). Anakinra blocks the biologic activity of naturally occurring IL-1, including inflammation and cartilage degradation associated with rheumatoid arthritis, by competitively inhibiting the binding of IL-1 to the interleukin-1 type receptor, which is expressed in many tissues and organs. IL-1 is produced in response to inflammatory stimuli and mediates various physiologic responses, including inflammatory and immunologic reactions. The biological properties of anakinra and the existing clinical and laboratory data favoring a derangement of the immune response in HS, prompted to investigate whether anakinra would be efficient in the management of patients with HS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Water for injection | Placebo comparator | Drug: Water for injectionPlacebo syringes will contain 0.67ml of sterile water for injection. This will be injected daily for 12 weeks. |
| Anakinra | Experimental | Drug: AnakinraAnakinra will be supplied in single use pre-filed glass syringes with 27-gauge needles. Anakinra syringe will contain 100mg of anakinra at a volume of 0.67 ml. This will be injected subcutaneously daily for 12 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- written informed consent provided by the patient;
- age above 18 years;
- diagnosis of hidradenitis suppurativa; and
- disease of Hurley II or III severity stage
Key exclusion criteria (12 listed)
- history of systemic lupus erythematosus, of rheumatoid arthritis of of seronegative inflammatory arthritis;
- any prior administration of any type of anti-TNF therapy over the last six months;
- administration of any live (attenuated) vaccine over the last 4 weeks;
- history of recurrent vein thrombosis or embolism compatible with anti-cardiolipin syndrome;
- any present or smoldering infection;
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 |
|---|---|---|
| Water for injectionAlso: Sterile waterPlacebo syringes will contain 0.67ml of sterile water for injection. This will be injecteda daily for 12 weeks. | Drug | Water for injection |
| AnakinraAlso: Recombinant human IL-1 receptor antagonistAnakinra will be supplied in single use pre-filed glass syringes with 27-gauge needles. Anakinra syringe will contain 100mg of anakinra at a volume of 0.67 ml. This will be injected subcutaneously daily for 12 weeks. | Drug | Anakinra |
Primary outcome
The efficacy of anakinra in patients with HS of Hurley II and III stage disease.
Time frame: 24 weeks
This will be defined by the changes of scoring parameters between the two study groups over visits.
3 secondary outcomes
The effect of anakinra in the ex vivo function of monocytes of patients with HS.
Time frame: 24 weeks
The effect of anakinra on the time to new exacerbation
Time frame: 24 weeks
The safety of anakinra in patients with hidradenitis suppurativa
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2015.
- Background: PubMed 18076705Giamarellos-Bourboulis EJ, Pelekanou E, Antonopoulou A, Petropoulou H, Baziaka F, Karagianni V, Stavrianeas N, Giamarellou H. An open-label phase II study of the safety and efficacy of etanercept for the therapy of hidradenitis suppurativa. Br J Dermatol. 2008 Mar;158(3):567-72. doi: 10.1111/j.1365-2133.2007.08372.x. Epub 2007 Dec 11.
- Background: PubMed 17199566Giamarellos-Bourboulis EJ, Antonopoulou A, Petropoulou C, Mouktaroudi M, Spyridaki E, Baziaka F, Pelekanou A, Giamarellou H, Stavrianeas NG. Altered innate and adaptive immune responses in patients with hidradenitis suppurativa. Br J Dermatol. 2007 Jan;156(1):51-6. doi: 10.1111/j.1365-2133.2006.07556.x.
- Background: PubMed 18400064Kurzen H, Kurokawa I, Jemec GB, Emtestam L, Sellheyer K, Giamarellos-Bourboulis EJ, Nagy I, Bechara FG, Sartorius K, Lapins J, Krahl D, Altmeyer P, Revuz J, Zouboulis CC. What causes hidradenitis suppurativa? Exp Dermatol. 2008 May;17(5):455-6; discussion 457-72. doi: 10.1111/j.1600-0625.2008.00712_1.x.
- Background: PubMed 19758320Pelekanou A, Kanni T, Savva A, Mouktaroudi M, Raftogiannis M, Kotsaki A, Giamarellos-Bourboulis EJ. Long-term efficacy of etanercept in hidradenitis suppurativa: results from an open-label phase II prospective trial. Exp Dermatol. 2010 Jun;19(6):538-40. doi: 10.1111/j.1600-0625.2009.00967.x. Epub 2009 Sep 16.
- Derived from this study: PubMed 26579854Tzanetakou V, Kanni T, Giatrakou S, Katoulis A, Papadavid E, Netea MG, Dinarello CA, van der Meer JWM, Rigopoulos D, Giamarellos-Bourboulis EJ. Safety and Efficacy of Anakinra in Severe Hidradenitis Suppurativa: A Randomized Clinical Trial. JAMA Dermatol. 2016 Jan;152(1):52-59. doi: 10.1001/jamadermatol.2015.3903.
- Hidradenitis suppurativa foundationLink provided by the sponsor.
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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.
Evangelos J Giamarellos-Bourboulis, MD, PhD study chair
University of Athens, Medical School, Greece
Dimitrios Rigopoulos, MD, PhD principal investigator
University of Athens, Medical School, Greece
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Water for injection and Anakinra in people with Hidradenitis Suppurativa, run by University of Athens at 2 sites in Greece.
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 4 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: finished, as of the sponsor's last update on 27 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Greece. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The efficacy of anakinra in patients with HS of Hurley II and III stage disease. (time frame: 24 weeks). 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 NCT01558375, which also lists 5 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 27 May 2015.