Safety and Efficacy of Brodalumab in Subjects With Axial Spondyloarthritis

• Register: EUCTR
• Last refreshed on: 24 August 2015
• Main ID: EUCTR2014-003701-15-ES
• Date of registration: 08/05/2015
• Prospective Registration: No
• Primary sponsor: Amgen Inc.
• Public title: Safety and Efficacy of Brodalumab in Subjects With Axial Spondyloarthritis
• Scientific title: A Randomized, Double-blind, Placebo-controlled Study With an Open Label Extension to Evaluate the Safety and Efficacy of Brodalumab in Subjects With Axial Spondyloarthritis
• Date of first enrolment: 05/05/2015
• Target sample size: 180
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003701-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: 16-week double-blind treatment period plus an open-label treatment period of up to 290 weeks If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Canada, Czech Republic, France, Germany, Japan, Poland, Russian Federation, Spain, United Kingdom, United States

Contacts

• Name: IHQ Medical Info - Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

• Name: IHQ Medical Info - Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
Subject is ? 18 years of age at time of screening

Disease Related
- Subject fulfills the ASAS classification criteria of axial spondyloarthritis (with the exception of the Crohn's disease criterion) for > 3 months with age of onset < 45 years of age
AS subjects: Subject has radiographic evidence of sacroiliitis grade ? 2 bilaterally or grade 3 to 4 unilaterally (image must have been obtained ? 4 years from time of screening; centrally read)
OR
nr-axSpA subjects: Subject does not have radiographic evidence of sacroiliitis grade ? 2 bilaterally or grade 3 to 4 unilaterally (image must have been obtained ? 6 months from time of screening; centrally read)
AND
presence of inflammatory lesions of sacroiliac joint by MRI of Spondyloarthritis Research Consortium of Canada (SPARCC) level ? 2 (confirmed by a central
imaging reader)
- Subject has Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ? 4 at screening and baseline
- Subject has spinal pain score (BASDAI question #2) ? 4 at screening and baseline
- Subject has had adequate therapeutic trial (at least 4 weeks) of ? 2 non-steroidal anti-inflammatory drugs (NSAIDs) at the maximum recommended dose unless contraindicated or subject is intolerant.
- For subjects receiving non-biologic DMARDs (eg, methotrexate not to exceed 25 mg per week; sulfasalazine not to exceed 3000 mg per day) subject has
received treatment for ? 3 months, with a stable dose for ? 4 weeks prior to initiation of IMP.
- For subject receiving oral corticosteroids: the subject must be on a stable dose (not to exceed the equivalent of 10 mg of prednisone per day) for ? 4 weeks prior to initiation of IMP.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 170
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
Disease Related: Complete ankylosis of the spine
Other Medical Conditions
- Subject has known history of active tuberculosis (TB)
- .Subject has a positive test for tuberculosis during screening
. Subjects with a positive purified protein derivative (PPD) and a history of Bacillus Calmette-Guérin vaccination are allowed with a negative Quantiferon test.
. Subjects with a positive PPD test or subjects with a positive or indeterminate Quantiferon test are allowed if they have ALL of the following:
? no symptoms per tuberculosis worksheet provided by Amgen
? documented history of a completed course of adequate prophylaxis per local standard of care prior to the start of IMP
? no known exposure to a case of active tuberculosis after most recent prophylaxis
? no evidence of active tuberculosis on chest radiograph within 3 months prior to the first dose of IMP
- Subject has a planned surgical intervention between baseline and week 16
- Subject has an active infection or history of infections as follows:
? any active infection for which systemic anti-infectives were used within 28 days prior to the first IMP dose
? a serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to the first IMP dose recurrent or chronic infections or other active infection that, in the opinion of the investigator, might cause this study to be detrimental to the subject
- Subject has any systemic disease considered by the investigator to be clinically significant and uncontrolled.
- Subject has positive hepatitis B surface antigen, hepatitis B core antibody or hepatitis C virus antibody serology
- Subject had myocardial infarction, unstable angina pectoris or stroke within the past 12 months prior to the first IMP dose
- Subject has any active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma.
- Subject has history of malignancy within the last 5 years EXCEPT treated and considered cured cutaneous basal or squamous cell carcinoma, in situ cervical cancer or in situ breast ductal carcinoma
- Subject has active Crohn's disease or a history of Crohn's disease
- Subject has active ulcerative colitis requiring daily use of immunosuppressive therapy
- Subject has had active fibromyalgia within the past 12 months
Laboratory Abnormalities
- Subject has any of the following laboratory abnormalities at screening:
? aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2x the upper limit of normal (ULN)
? serum direct bilirubin ? 1.5 mg/dL (25.7 ?mol/L)
? white blood cell (WBC) count < 3.00 x 109/L
? absolute neutrophil count (ANC) < 2.00 x 109/L
- Subject has any other laboratory abnormality, which, in the opinion of the investigator, will prevent the subject from completing the study or will interfere with the interpretation of the study results
Washouts or Other Treatments
- Subject has a prior history of >1 anti-TNF therapy for ankylosing spondylitis
- Subject has used commercially available or investigational biologic therapies for ankylosing spondylitis
General
- Subject has a history or evidence of suicidal ideation (severity of 4 or 5) or any suicidal behavior based on an assessment with the electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) at screening or at baseline
- Subject has a history or evidence of a psychiatric disorder or substance abuse or any other mental health disorder that, in the opinion of the investigator, would pose a risk to subject s

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Axial Spondyloarthritis
MedDRA version: 18.0 Level: PT Classification code 10051265 Term: Spondyloarthropathy System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: brodalumab (140mg/ml)
Product Code: AMG 827
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: brodalumab
CAS Number: 1174395-19-7
Current Sponsor code: AMG 827
Other descriptive name: BRODALUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 140-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Product Name: brodalumab (70mg/0.5ml)
Product Code: AMG 827
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: brodalumab
CAS Number: 1174395-19-7
Current Sponsor code: AMG 827
Other descriptive name: BRODALUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 140-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: To evaluate the efficacy of brodalumab in ankylosing spondylitis (AS) compared to placebo, as measured by the proportion of AS subjects achieving an Assessment of SpondyloArthritis international Society (ASAS) 20 response at week 16.

Primary end point(s): ASAS 20 in AS subjects at week 16

Timepoint(s) of evaluation of this end point: at week 16

Secondary Objective: ? To evaluate the efficacy of brodalumab in AS subjects on Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) change from baseline at week 16
? To evaluate the efficacy of brodalumab in the pooled population (AS and non-radiographic axial spondyloarthritis [nr-axSpA] subjects) on ASAS 20 at week 16
? To evaluate the efficacy of brodalumab in AS subjects as measured by ASAS 40 at week 16
? To evaluate the efficacy of brodalumab in the anti-TNF-experienced and anti-TNF-naïve subgroups as measured by ASAS 20 at week 16
? To describe the effect of brodalumab in subjects with nr-axSpA as measured by ASAS 20 at week 16

Secondary Outcome(s)

Secondary end point(s): ? ASDAS-CRP change from baseline in AS subjects at week 16
? ASAS 20 at week 16 in the pooled population (AS and nr-axSpA subjects)
? ASAS 40 at week 16 in AS subjects
? ASAS 20 at week 16 in anti-TNF-naïve AS subjects
? ASAS 20 at week 16 in anti-TNF-experienced AS subjects
? ASAS 20 at week 16 in nr-axSpA subjects

Timepoint(s) of evaluation of this end point: at week 16

Secondary ID(s)

2014-003701-15-GB

20101228

Source(s) of Monetary Support

Amgen Inc