Trial document





This trial has been registered retrospectively.
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  DRKS00000071

Trial Description

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Title

Phase III, multi-center, randomized, double-blind, placebo-controlled study for treatment of juvenile ankylosing spondylitis with Adalimumab

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Trial Acronym

[---]*

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URL of the Trial

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Brief Summary in Lay Language

This study aims at patients with juvenile ankylosing spondylitis (M. Bechterew), who did not respond to therapy with nonsteroidal anti-inflammatory drugs.
The TNF inhibitor Adalimumab is approved in the therapy of ankylosing spondylitis in adult patients, the treatment requires a subcutaneous injection of Adalimumab every other week.
This study designed to evaluate the efficacy and safety of treatment of juvenile ankylosing spondylitis with adalimumab.
In the first 12 week period patients will receive either Adalimumab or placebo, in the following 12 week period all patients will receive Adalimumab and can possibly profit from treatment.
During the study monthly visits at the study centre are required.

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Brief Summary in Scientific Language

This randomized, double-blind, placebocontrolled study is designed to assess efficacy and safety of treatment of juvenile ankylosing spondylitis with Adalimumab, a TNF inhibitor. In the therapy of ankylosing spondylitis in adult patients Adalimumab has been shown to be effective and is already approved.
Study design: In the first placebo-controlled 12 week period subjects who meet all entry criteria will be randomized to either 40 mg Adalimumab or placebo injected subcutaneously every other week. In the following 12 week period all patients will receive 40mg of Adalimumab subcutaneously every other week.
Physical examinations, measures of disease activity and laboratory tests are to be performed at screening, baseline and every 4 weeks.

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Organizational Data

  •   DRKS00000071
  •   2009/02/06
  •   [---]*
  •   yes
  •   Approved
  •   2008035, Ethikkommission der Ärztekammer Nordrhein
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Secondary IDs

  •   2007-003358-27 
  •   544/01 
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Health Condition or Problem studied

  •   juvenile ankylosing spondylitis
  •   M08.1 -  Juvenile ankylosing spondylitis
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Interventions/Observational Groups

  •   Adalimumab 40mg s.c. every other week
  •   Placebo s.c. every other week
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Double or multiple blind
  •   [---]*
  •   Placebo
  •   Other
  •   Parallel
  •   III
  •   [---]*
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Primary Outcome

- to demonstrate the superiority of adalimumab with respect to the ASAS Working Group response criterion ASAS40 as compared to placebo
- to contrast the safety profile of adalimumab with placebo in subjects with juvenile ankylosing spondylitis.

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Secondary Outcome

- to show improvement of each of the 4 categories contributing to the ASAS40 criterion (spinal inflammation, back pain, patient's global assessment, physical function)
- to show superiority of adalimumab with respect to the ACR Ped 30 response criterion as compared to placebo
- to show improvement of each of the 6 categories contributing to the ACR Ped Score (physician's global assessment, parents' global assessment of subject's overall well-being, number of active joints, number of joints with limitation of motion, physical function, CRP).

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • [---]*
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Recruitment

  •   Actual
  •   2008/07/02
  •   50
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   12   Years
  •   18   Years
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Additional Inclusion Criteria

- IN1 Parents / legal guardian are willing to participate in the study and signed voluntarily the Informed Consent form.

- IN2 Parents / legal guardian are willing to actively supervise storage and administration of study drug and to ensure that the time of each dose is accurately recorded in the subject's diary.

- IN3 Patient and parents / legal guardian agree to comply with study requirements and are able to be at the clinic for all required study visits.

- IN4 Patient is at least 12 years old and has not reached his 18th birthday.

- IN5 The weight of the patient is > 30 kg.

- IN6 IN FEMALE PATIENT IN WHOM MENARCHE HAS OCCURRED
> Negative serum pregnancy test prior to administration of study medication.
> Willingness to use an adequate method of contraception
Adequate contraception can include abstinence if the investigator deems appropriate.
- IN7 Patient has a diagnosis of juvenile ankylosing spondylitis, i.e.
A bilateral active sacroiliitis confirmed by magnetic resonance imaging is present
OR
B unilateral active sacroiliitis confirmed by magnetic resonance imaging is present, and patient has active peripheral joint disease restricted to the lower extremities (hip, knee, ankle)
AND at least 1 clinical criterion is fulfilled:
1. limitation of lumbar spine motion in all three planes
2. pain or history of pain at the dorsolumbar junction of the lumbar spine
3. limitation of chest expansion to 2.5 cm or less at the level of the fourth intercostal space.

- IN8 Patient has active disease, i.e.
1. spinal inflammation score of at least 3
AND at least 2 of the following domains:
2. back pain score of at least 3
3. patient global assessment of disease activity of at least 3
4. physical function score of at least 3.
- IN9 The disease has been refractory to at least two different non-steroidal antiphlogistic drugs given at appropriate dosage and for appropriate period of time.

- IN10 Patient has not been treated with either etanercept or infliximab or adalimumab or anakinra at any time for any period.

- IN11 Patient is able and willing to self-administer sc injections or has a suitable person at his disposal to administer sc injections.

- IN12 Patient must be evaluated for active or latent TB infection according to the instructions of the protocol. If applicable: Guidelines regarding the treatment of latent TB must be followed prior to the administration of study medication.

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Exclusion Criteria

- EX1 Patient has been diagnosed to have systemic onset of JRA / JIA or has active systemic features including fever or rash.

- EX2 Patient has active uveitis within a period of 4 weeks prior to the first administration of study medication.

- EX3 Pregnant or breast feeding female.

- EX4 Female not willing to use appropriate contraception or sexual abstinence.

- EX5 Chronic or active infectious disease, especially patient is positive for the hepatitis B surface antigen.

- EX6 Preceding severe infectious disease during a period of 3 months prior to the first administration of study medication.

- EX7 Preceding diagnosis of tuberculosis or any opportunistic infection including herpes zoster at any time.

- EX8 Any preceding diagnosis of malignancy.

- EX9 Patient has a history of any chronic disease other than JAS, JRA / JIA, especially chronic renal disease, liver disease, hematological, gastrointestinal, pulmonary, cardiological or neurological disease, which in the opinion of the investigator may influence the efficacy or safety of the study medication or which in the opinion of the investigator leads to an unacceptable risk for the patient if he participates in the study.

- EX10 Patient had a significant illness during a period of 4 weeks prior to the first administration of study medication other than JAS-related.

- EX11 Patient is abusing alcohol or drugs.

- EX12 Patient has been treated with antimalarials, gold salts, sulphasalazine, azathioprine, penicillamine, leflunomide, cyclosporine A, intravenous immunoglobulin, or methotrexate within 4 weeks prior to the first administration of study medication, or plans to begin the intake of these drugs.

- EX13 Patient has been exposed to etanercept or infliximab or adalimumab or anakinra before receiving the first dose of study medication.

- EX14 Patient has begun the intake or changed the dose regimen of oral corticosteroids within 4 weeks before Screening, doses of up to 0.2 mg/kg or 10 mg prednisone or equivalent per day, whichever is less, are allowed.

- EX15 Patient plans to change dosing of oral corticosteroids within the study period.

- EX16 Patient has received i.v., i.m., i.a. or soft tissue injections of corticosteroids within 4 weeks before first administration of study medication.

- EX17 Patient has previously been admitted to this study.

- EX18 Patient has been treated with any other investigational agent within 30 days or 5 half-lifes of the agent, whichever is longer, prior to the screening evaluation.

- EX19 Patient has been treated with any investigational biologic agent within 6 months prior to the screening evaluation.

- EX20 Demonstration of clinically significant deviations in any of the following laboratory parameters:
> platelet count < 100.000/mm3
> total white cell count < 4000 cells/mm3
> neutrophils < 1000 cells/mm3
> hematocrit < or = 24%
> AST or ALT or serum bilirubin > 2x the upper limit of normal
> glomerular filtration rate GFR < 90 mL/min / 1.73 m2 BSA
[GFR (mL/min / 1.73 m2 BSA) = 0.55 x height (cm) / plasma creatinine (mg/dL)]

- EX21 Patient has a history of an expanding CNS neoplasm, active CNS infection, demyelinating disease, degenerative neurological disease or any progressive CNS disease.

- EX22 Patient has a poorly controlled diabetes.

- EX23 Any concurrent medical condition which would, in the investigator's opinion, compromise the patient's ability to tolerate the study drug or would make the patient unable to comply with the protocol.

- EX24 Patient has a history of or current psychiatric illness that would interfere with ability to comply with protocol requirements or give informed consent.

- EX25 Patient has a recent history of alcohol or drug abuse within the past 6 months that would interfere with ability to comply with protocol requirements.

- EX26 Any other inability to comply with the study requirements.

- EX27 Any contraindication listed in the German 'Fachinformation' of the drug Humira®.

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Addresses

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    • Asklepios Klinik Sankt Augustin
    • Mr.  Prof. Dr. med.  Gerd  Horneff 
    • Arnold-Janssen-Straße 29
    • 53757  Sankt Augustin
    • Germany
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    • Asklepios Klinik Sankt Augustin
    • Ms.  Sigrid  Fitter 
    • Arnold-Janssenstr. 29
    • 53757  Sankt Augustin
    • Germany
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    • Asklepios Klinik Sankt Augustin
    • Ms.  Dr. med.  Ariane  Klein 
    • Arnold-Janssen-Straße 29
    • 53757  Sankt Augustin
    • Germany
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Sources of Monetary or Material Support

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    • Abott GmbH & Co. KG
    • Max-Planck-Ring 2
    • 65205  Wiesbaden
    • Germany
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    •   06112 580
    •   [---]*
    •   [---]*
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Status

  •   Recruiting stopped after recruiting started
  •   2011/03/24
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.