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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01061723




Registration number
NCT01061723
Ethics application status
Date submitted
2/02/2010
Date registered
3/02/2010
Date last updated
8/08/2017

Titles & IDs
Public title
Dose Ranging Study to Evaluate the Efficacy and Safety of SAR153191 (REGN88) in Patients With Ankylosing Spondylitis
Scientific title
A Randomized Double Blind-placebo Controlled Dose Ranging Study to Evaluate the Efficacy and Safety of SAR153191 in Participants With Ankylosing Spondylitis (AS)
Secondary ID [1] 0 0
2009-016068-35
Secondary ID [2] 0 0
DRI11073
Universal Trial Number (UTN)
Trial acronym
ALIGN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ankylosing Spondylitis 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Sarilumab
Treatment: Drugs - Placebo

Placebo Comparator: Placebo - Placebo (for sarilumab) weekly (qw) for 12 weeks.

Experimental: Sarilumab 100 mg q2w - Sarilumab 100 mg Subcutaneous (SC) injection alternating with placebo every other week (q2w) for 12 weeks.

Experimental: Sarilumab 150 mg q2w - Sarilumab 150 mg SC injection alternating with placebo q2w for 12 weeks.

Experimental: Sarilumab 100 mg qw - Sarilumab 100 mg SC injection qw for 12 weeks.

Experimental: Sarilumab 200 mg q2w - Sarilumab 200 mg SC injection alternating with placebo q2w for 12 weeks.

Experimental: Sarilumab 150 mg qw - Sarilumab 150 mg SC injection qw for 12 weeks.


Treatment: Drugs: Sarilumab
Pharmaceutical form: Solution for injection
Route of administration: Subcutaneous

Treatment: Drugs: Placebo
Pharmaceutical form: Solution for injection
Route of administration: Subcutaneous

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Who Achieved 20% Response According to the Assessment in Ankylosing Spondylitis (AS) Working Group Criteria for Response (ASAS20) at Week 12 - Clinical response to treatment for ASAS20 was assessed according to ASAS20 criteria. Treatment response for ASAS20 was defined as an improvement by a decrease of =20% and =1unit on a 0 (no pain) - 10 (most severe pain) numerical rating scale (NRS) in at least 3 of the 4 ASAS improvement criteria (ASAS-IC) domains: assessment of physical function (measured by Bath Ankylosing Spondylitis Functional Index [BASFI]), back pain (0-10 NRS), participant global assessment (0-10 NRS) and inflammation (measured as the mean of the last 2 Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] questions) and no worsening (increase in score) of =20% and =1 unit on a 0-10 NRS in the remaining 4th domain.
Timepoint [1] 0 0
Baseline to Week 12 (Last Observation Carried Forward [LOCF])
Secondary outcome [1] 0 0
Percentage of Participants Who Achieved 40% Response According to the Assessment in AS Working Group Criteria for Response (ASAS40) at Week 12 - Clinical response to treatment for ASAS40 was assessed according to ASAS40 criteria. Treatment response for ASAS40 was defined as an improvement by a decrease of =40% and =2 units on a 0 (no pain)-10 (most severe pain) NRS in at least 3 of the 4 ASAS-IC domains (participant global assessment, back pain, physical function and inflammation) and no worsening (increase in score) at all in the remaining 4th domain.
Timepoint [1] 0 0
Baseline to Week 12 (LOCF)
Secondary outcome [2] 0 0
Percentage of Participants Who Achieved Partial Remission According to the Assessment in AS Working Group Criteria for Response (ASAS) at Week 12 - Participants were classified as having achieved ASAS partial remission if they had a value = 2 units on a 0 -10 NRS in each of the 4 domains: (participant global assessment, back pain, physical function and inflammation) of the ASAS-IC.
Timepoint [2] 0 0
Baseline to Week 12 (LOCF)
Secondary outcome [3] 0 0
Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 12 - ASDAS consists of five components: (Total back pain assessed by BASDAI question 2 on a 0 [no pain] - 10 [most severe pain] NRS, participant global of disease activity on a 0 [none] - 10 [severe] NRS, peripheral pain/swelling assessed by BASDAI question 3 on a 0 [none] - 10 [most severe pain] NRS, duration of morning stiffness assessed by BASDAI question 6 on a NRS from 0 [0 hour] - 10 [2 or more hours] and hs-CRP in mg/L). ASDAS score was calculated as follows: 0.121 x total back pain + 0.110 x participant global of disease activity + 0.073 x peripheral pain/swelling + 0.058 x duration of morning stiffness + 0.579 x ln(CRP + 1). The scores were categorized as: inactive disease (< 1.3), moderate (1.3 - < 2.1), high (2.1 - 3.5) and very high disease activity (> 3.5).
Timepoint [3] 0 0
Baseline, Week 12 (LOCF)
Secondary outcome [4] 0 0
Change From Baseline in BASDAI Score at Week 12 - BASDAI comprises of a 0 (no pain) -10 (very severe pain) NRS, used to answer 6 questions (Q) related to symptoms of AS (fatigue/tiredness, neck, back or hip pain, pain / swelling in joints, discomfort in tender areas, morning stiffness duration and morning stiffness severity). The BASDAI total score was calculated by computing the mean of Q5 and Q6 and adding it to the sum of Q1 to Q4. This score was then divided by 5. BASDAI total score=Q1+Q2+Q3+Q4+[Q5+Q6/2]/5. The total BASDAI score ranges from 0=none to 10=severe, where lower score indicated less disease activity.
Timepoint [4] 0 0
Baseline, Week 12 (LOCF)
Secondary outcome [5] 0 0
Change From Baseline in Range of Motion Assessed by the Bath AS Metrology Index (BASMI) at Week 12 - The range of motion was measured by the BASMI (11-point scale) including chest expansion in cm. It composed of 5 clinical measurements associated with a score: tragus to wall distance, modified schober's test, lateral spinal flexion, intermalleolar distance and cervical rotation. BASMI score was calculated by dividing the total of the score by 5, and the score ranges from 0-10. Higher BASMI score indicates more severe limitation of movement.
Timepoint [5] 0 0
Baseline, Week 12 (LOCF)
Secondary outcome [6] 0 0
Change From Baseline in Magnetic Resonance Imaging (MRI) Score of the Spine Assessed by the Berlin Modification of the AS Spine MRI-active (ASspiMRI-a) Score at Week 12 - ASspiMRI-a scoring system was used on all MRIs to score the level of the disease. MRIs were obtained using 1.0 or 1.5 Tesla scanners and phased array coils. Sagittal images of the upper (C2 to T10) and lower (T8 to S1) spine were used using both T1 weighted spin echo and fat saturated Short Tau Inversion Recovery (STIR) sequences. Each vertebral body unit was given an activity score based on the amount of bone marrow edema or erosion. Both T1 and STIR sequences were analyzed for change. Total spine ASspiMRI-a score in the Berlin modification range from 0 to 69 with higher scores indicating higher disease activity. A negative value in total spine ASspiMRI-a score change from baseline indicates an improvement from baseline. The higher the negative value the higher the reduction of inflammation.
Timepoint [6] 0 0
Baseline, Week 12
Secondary outcome [7] 0 0
Percentage of Participants Who Achieved ASAS 5/6 Improvement Criteria at Week 12 - ASAS 5/6 responder had an improvement of 20% in 5 of 6 domains (physical function, back pain, participant global assessment, inflammation, spinal mobility and acute phase reactants) of ASAS-IC without deterioration in the 6th domain. Spinal mobility was assessed by the mean of the 5 BASMI scores on the 11-point scale (score ranges from 0-10) and the hs-CRP for the acute phase reactant.
Timepoint [7] 0 0
Baseline to Week 12 (LOCF)
Secondary outcome [8] 0 0
Change From Baseline in Chest Expansion at Week 12 - The difference between maximal inspiration and expiration to the nearest 0.1 cm was recorded. The best of 2 tries were recorded.
Timepoint [8] 0 0
Baseline, Week 12 (LOCF)
Secondary outcome [9] 0 0
Change From Baseline in Swollen Joint Index at Week 12 - 44 swollen joints were examined including sternal, clavicular, elbow, shoulder, wrist, knee, metacarpophalangian, interphalangian, metatarpophalangian and metatarsophalangeal joints.
Timepoint [9] 0 0
Baseline, Week 12 (LOCF)
Secondary outcome [10] 0 0
Change From Baseline in Hs-CRP at Week 12 - Participant's blood samples were collected at screening, baseline before dosing and at every visit to evaluate the level of hs-CRP. The hs-CRP is a protein marker in the blood associated with inflammation with higher values indicating a greater degree of inflammation.
Timepoint [10] 0 0
Baseline, Week 12 (LOCF)
Secondary outcome [11] 0 0
Change From Baseline in ASAS Individual Components at Week 12 - ASAS consists of 4 individual components: Participant global assessment to assess the disease activity over the last week on a 0 (no pain) - 10 (severe pain) NRS; back pain which consist of the mean of the nocturnal back pain and the total back pain at every visit on a 0 (no pain) - 10 (most severe pain) NRS; inflammation measured as the mean of the last 2 BASDAI questions (intensity and duration of morning stiffness) and physical function measured as mean of 10 scores of BASFI at every visit on 0 (easy) -10 (impossible) NRS. Lower score corresponds to a better functioning.
Timepoint [11] 0 0
Baseline, Week 12 (LOCF)

Eligibility
Key inclusion criteria
Inclusion criteria:

- Diagnosis of AS according to the New York modified criteria

- Participants must had an adequate trial of at least 2 different Non-Steroidal
Anti-Inflammatory Drugs (NSAIDs) taken for at least 2 weeks in each case and, on a
stable dose for =2 weeks or be intolerant to NSAIDs

- Participants must had active AS for =3 months before screening and active disease must
be present at screening and at baseline; Active AS being defined by:

- Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of =4
(Numerical Rating Scale 0-10)

- Total back pain score =4 (Numerical Rating Scale 0-10)

Participants treated with corticosteroid must be on a stable dose for =2 weeks prior to
baseline

Participants treated with the Disease Modifying Anti-Rheumatic Drugs (DMARDs)
hydroxychloroquine, sulfasalazine and methotrexate (MTX) must be on stable dose =12 weeks
prior to baseline
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- <18 years old or =75 years old

- Complete fusion of the spine

- Past history of non response to any anti-Tumor Necrosis Factors (TNFs) treatment or
non response to any other biological treatment for AS

- Any past or current treatment with anti-TNF's or any biological agent within 3 months
prior to screening

- Treatment with DMARDs except for hydroxychloroquine, sulfasalazine and MTX

- MTX >25 mg/week

- hydroxychloroquine >400 mg/day

- Sulfasalazine >3 g/day

- Treatment with oral prednisone or equivalent corticosteroids >10 mg/day within 6 weeks
prior to screening

- Use of intramuscular or intra-articular corticosteroids within the last 4 weeks before
screening

- Previous treatment with cyclosporine, azathioprine

The above information was not intended to contain all considerations relevant to a
participant's potential participation in a clinical trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 036001 - East Malvern
Recruitment hospital [2] 0 0
Investigational Site Number 036003 - Hobart
Recruitment hospital [3] 0 0
Investigational Site Number 036004 - Shenton Park
Recruitment hospital [4] 0 0
Investigational Site Number 036002 - Woolloongabba
Recruitment postcode(s) [1] 0 0
3145 - East Malvern
Recruitment postcode(s) [2] 0 0
7001 - Hobart
Recruitment postcode(s) [3] 0 0
6008 - Shenton Park
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
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Idaho
Country [5] 0 0
United States of America
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Illinois
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United States of America
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Kansas
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United States of America
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Maryland
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United States of America
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Massachusetts
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United States of America
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Michigan
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Missouri
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New Jersey
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New York
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Ohio
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United States of America
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Oklahoma
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Pennsylvania
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Texas
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United States of America
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Virginia
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Austria
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Graz
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Austria
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Wien
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Belgium
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Brussels
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Belgium
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Genk
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Belgium
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Gent
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Belgium
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Leuven
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Belgium
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Liège
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Canada
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London
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Canada
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Montreal
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Canada
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Newmarket
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Canada
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Pointe-Claire
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Canada
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Quebec
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Canada
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Saskatoon
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Toronto
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Canada
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Trois-Rivières
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Canada
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Vancouver
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Czechia
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Brno
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Czechia
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Hlucin
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Czechia
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Hradec Kralove
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Czechia
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Praha 2
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Czechia
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Uherske Hradiste
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France
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Besancon
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France
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Bordeaux
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France
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Creteil Cedex
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France
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Paris
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Germany
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Berlin
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Germany
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Erlangen
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Germany
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Frankfurt Am Main
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Germany
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Hamburg
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Germany
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Herne
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Hungary
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Budapest
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Hungary
State/province [49] 0 0
Debrecen
Country [50] 0 0
Hungary
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Sátoraljaújhely
Country [51] 0 0
Hungary
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Veszprém
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Lithuania
State/province [52] 0 0
Kaunas
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Lithuania
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Vilnius
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Netherlands
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Amsterdam
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Netherlands
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Nijmegen
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Poland
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Bialystok
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Poland
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Krakow
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Lublin
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Poland
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Torun
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Poland
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Warszawa
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Spain
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Barcelona
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Spain
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La Coruña
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Spain
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Madrid
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Spain
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Sevilla
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Turkey
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Ankara
Country [66] 0 0
Turkey
State/province [66] 0 0
Izmir

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sanofi
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Regeneron Pharmaceuticals
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Primary objective:

- to evaluate the efficacy of Sarilumab in participants with Ankylosing Spondylitis (AS)
using the assessment in AS working group criteria (ASAS) 20% response criteria (ASAS20)

Secondary objectives:

- to demonstrate that Sarilumab was effective on:

- assessment of higher level of response [ASAS 40% response criteria (ASAS40)]

- partial remission

- disease activity

- range of motion

- Magnetic Resonance Imaging (MRI) of the spine

- to assess the safety and tolerability of Sarilumab in participants with AS as well as
the pharmacokinetic profile of Sarilumab in participants with AS
Trial website
https://clinicaltrials.gov/show/NCT01061723
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications