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Trial record 7 of 13 for:    Ankylosing Spondylitis | Secukinumab | novartis [Lead]

Study to Demonstrate the Efficacy, Safety and Tolerability of an Intravenous Regimen of Secukinumab Compared to Placebo in Subjects With Active axSpA

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04156620
Recruitment Status : Recruiting
First Posted : November 7, 2019
Last Update Posted : March 12, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this global study is to demonstrate the efficacy, safety, and tolerability of an intravenous (i.v.) regimen of secukinumab compared to placebo in subjects with active axSpA at Week 16 despite current or previous NSAID, DMARD and/or anti Tumor Necrosis Factor (TNF) therapy. In addition, to further support efficacy and safety of an i.v. regimen, data will be collected for up to 52 weeks of treatment. Efficacy and safety data may be used to support the registration of i.v. secukinumab in the US and other countries for treatment of subjects with active axSpA.

Condition or disease Intervention/treatment Phase
Ankylosing Spondylitis or Non-radiographic Axial Spondyloarthritis Drug: Secukinumab Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: This is a double-blind, randomized treatment trial. Subjects, investigators, investigator staff and persons performing the assessments, will remain blind to the identity of the treatment from the time of randomization until database lock, using the following methods: (1) Randomization data are kept strictly confidential until the time of unblinding and will not be accessible by anyone else involved in the study with the exception of the bioanalyst, (2) the identity of the treatments will be concealed by the use of study treatment in form of vials, filled with secukinumab or placebo that are identical in appearance.
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase III Multicenter Study of Intravenous Secukinumab to Compare Efficacy at 16 Weeks With Placebo and to Assess Safety and Tolerability up to 52 Weeks in Subjects With Active Ankylosing Spondylitis or Non-radiographic Axial SpondyloArthritis
Actual Study Start Date : December 11, 2019
Estimated Primary Completion Date : August 9, 2021
Estimated Study Completion Date : September 19, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Secukinumab

Arm Intervention/treatment
Experimental: Secukinumab
Secukinumab intravenous (i.v.) regimen
Drug: Secukinumab
The subjects will receive secukinumab 6 mg/kg i.v. at randomization (Baseline (BSL) visit), followed by the administration of secukinumab 3 mg/kg i.v. every four weeks starting at Week 4 through Week 48 (exposure through Week 52)
Other Name: AIN457

Placebo Comparator: Placebo
Placebo intravenous (i.v.) regimen
Drug: Placebo
The subjects will receive i.v. placebo at randomization (BSL visit), Weeks 4, 8, and 12 , followed by the administration of secukinumab 3 mg/kg i.v. at Week 16 and every four weeks through Week 48 (exposure through Week 52)




Primary Outcome Measures :
  1. The proportion of subjects achieving an ASAS40 (Assessment of SpondyloArthritis International Society criteria) response. [ Time Frame: Week 16 ]
    ASAS40 response at Week 16, defined as improvement of ≥ 40% and an absolute improvement from baseline of ≥20 units (range 0-100) in ≥ 3 of the following 4 domains: back pain [10 cm visual analogue scale (VAS)], patient global assessment of disease activity (10 cm VAS), physical function (BASFI; range 0-100) and inflammation (mean score of items 5 and 6 of the BASDAI; both 10 cm VAS) without any worsening in the remaining domain


Secondary Outcome Measures :
  1. The proportion of subjects achieving Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-Reactive Protein (CRP) major improvement [ Time Frame: Week 16 ]
    ASDAS-CRP major improvement defined as a change (decrease) in the score of at least 2.0 units

  2. The change from baseline in total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [ Time Frame: Week 16 ]
    Change from baseline in total BASDAI

  3. The proportion of subjects meeting the ASAS 5/6 response criteria [ Time Frame: Week 16 ]
    Subjects achieving ASAS 5/6 response defined as: improvement of ≥20% in at least five of six domains

  4. The change from baseline on Bath Ankylosing Spondylitis Functional Index (BASFI) [ Time Frame: Week 16 ]
    Change from baseline of BASFI

  5. The change from baseline in Short Form-36 Physical Component Summary (SF-36 PCS) [ Time Frame: Week 16 ]
    Change from baseline in SF-36 PCS

  6. The change from baseline in Ankylosing Spondylitis Quality of Life (ASQoL) scores [ Time Frame: Week 16 ]
    Change from baseline in ASQoL

  7. The change from baseline in high sensitivity C-Reactive Protein (hsCRP) [ Time Frame: Week 16 ]
    Change from baseline in hsCRP

  8. The proportion of subjects achieving an ASAS20 response [ Time Frame: Week 16 ]
    The ASAS Response Criteria (ASAS20) is defined as an improvement of ≥20% and ≥1 unit on a scale of 10 in at least three of the four main domains and no worsening of ≥20% and ≥1 unit on a scale of 10 in the remaining domain

  9. The proportion of subjects achieving Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-Reactive Protein (CRP) inactive disease [ Time Frame: Week 16 ]
    ASDAS-CRP inactive disease as defined by an ASDAS-CRP score below 1.3

  10. The proportion of subjects achieving ASAS partial remission [ Time Frame: Week 16 ]
    ASAS partial remission criteria are defined as a value not above 2 units in each of the four main ASAS domains on a scale of 0-10

  11. The change from baseline in Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: Week 16 ]
    Change from baseline in PSQI



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects eligible for inclusion in this study must meet all of the following criteria:

  1. Subject must be able to understand and communicate with the investigator, comply with the requirements of the study. and must give written, signed and dated informed consent before any study assessment is performed
  2. Male and non-pregnant, non-lactating female patients ≥ 18 years of age
  3. Diagnosis of axSpA according to ASAS criteria

    1. Inflammatory back pain for at least 6 months
    2. Onset before 45 years of age
  4. For subjects with AS: Diagnosis of AS with prior documented radiologic evidence (x-ray or radiologist's report) fulfilling the Modified New York criteria for AS
  5. For subjects with nr-axSpA:

    X-ray of SIJ negative (centrally read) for AS by Modified NY criteria AND

    1. Sacroiliitis on MRI (centrally read) with ≥ 1 SpA feature OR HLA-B-27 positive with ≥2 SpA features AND
    2. Objective signs of inflammation at screening, evident by either MRI with SIJ inflammation (centrally read) AND / OR hsCRP > ULN (as defined by the central lab)
  6. Active axial SpA assessed by BASDAI ≥4 cm (0-10 cm) at Baseline
  7. Spinal pain as measured by BASDAI question #2 ≥ 4 cm (0-10 cm) at Baseline
  8. Total back pain as measured by VAS ≥ 40 mm (0-100 mm) at Baseline
  9. Subjects should have had inadequate response or failure to respond to at least 2 NSAIDs at an approved dose for a minimum of 4 weeks in total and a minimum of 2 weeks for each NSAID prior to randomization, or less than 4 weeks if therapy had to be withdrawn due to intolerance, toxicity or contraindications
  10. Subjects who are regularly taking NSAIDs (including COX-1 or COX-2 inhibitors) as part of their AS or nr-axSpA therapy are required to be on a stable dose for at least 2 weeks before randomization
  11. Subjects who are intolerant or have been inadequate responders to a TNF inhibitor (not more than one) will be allowed to enter into the study (not more than 20% per group). They must have experienced an inadequate response to previous or current treatment at an approved dose for at least 3 months prior to randomization, or have been intolerant to at least one administration of an anti-TNF agent. These subjects will undergo an appropriate wash-out period prior to randomization, if required

    1. 4 weeks for Enbrel® (etanercept) - with a terminal half-life of 102 ± 30 hours
    2. 8 weeks for Remicade® (infliximab) - with a terminal half-life of 8.0-9.5 days
    3. 10 weeks for Humira® (adalimumab) - with a terminal half-life of 10-20 days (average 2 weeks)
    4. 10 weeks for Simponi® (golimumab) - with a terminal half-life of 11-14 days
    5. 10 weeks for Cimzia® (certolizumab) - with a terminal half-life of 14 days
  12. Subjects taking methotrexate (MTX) (≤ 25 mg/week ) or sulfasalazine (≤ 3 g/day) are allowed to continue their medication and must have taken it for at least 3 months and have to be on a stable dose for at least 4 weeks prior to randomization. Subjects on MTX must be on folic acid supplementation before randomization
  13. Subjects who are on a conventional DMARD other than MTX or sulfasalazine must discontinue the DMARD 4 weeks prior to randomization, except for leflunomide, which must be be discontinued 8 weeks prior to randomization, unless a cholestyramine washout has been performed
  14. Subjects taking systemic corticosteroids must be on a stable dose of ≤10 mg/day prednisone or equivalent for at least 2 weeks before randomization

Exclusion Criteria:

Subjects meeting any of the following criteria are not eligible for inclusion in this study

  1. Subjects with total ankylosis of the spine
  2. Chest x-ray or MRI with evidence of ongoing infectious or malignant process obtained within 3 months of screening and evaluated by a qualified physician
  3. Subjects taking moderate and high potency opioid analgesics (e.g. methadone, hydromorphone, morphine)
  4. Presence of significant medical problems which at investigator's discretion, will prevent the subject from participating in the study, including but not limited to the following: Subjects with severely reduced kidney function (estimated glomerular filtration rate (eGFR) <29 ml/min/1.73m2), history of renal trauma, glomerulonephritis, or patients with one kidney only, or a serum creatinine level exceeding 1.5 mg/dl (132.6 μmol/L)
  5. Any therapy by intra-articular injections (e.g. corticosteroid) within 4 weeks before Randomization
  6. Underlying conditions (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which in the opinion of the investigator significantly immunocompromises the subject and/or places the subject at unacceptable risk for receiving an immunomodulatory therapy
  7. Any medical or psychiatric condition which, in the Investigator's opinion, would preclude the participant from adhering to the protocol or completing the study per protocol
  8. Active systemic infections during the last two weeks (exception: common cold) prior to randomization or any infection that reoccurs on a regular basis
  9. History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection as defined by either a positive purified protein derivative (PPD) skin test (the size of induration will be measured after 48-72 hours, and a positive result is defined as an induration of ≥ 5 mm or according to local practice/guidelines) or a positive QuantiFERON TB-Gold test as indicated in the assessment schedule in Table 8-1. Subjects with a positive test may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the subject has no evidence of active tuberculosis. If presence of latent tuberculosis is established, then treatment according to local country guidelines must have been initiated
  10. Past medical history of infection with HIV or hepatitis B prior to randomization or active infection or on treatment for Hepatitis C at randomization
  11. History of lymphoproliferative disease or any known malignancy, or history of malignancy of any organ system treated or untreated within the past 5 years, regardless of whether there is evidence of local recurrence or metastases (except for skin Bowen's disease, or basal cell carcinoma or actinic keratoses that have been treated with no evidence of recurrence in the past 12 weeks; carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed)
  12. Use or planned use of prohibited concomitant medication (see Section 6.2.2)
  13. Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor tolerability or lack of access to veins)
  14. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test
  15. History or evidence of ongoing alcohol or drug abuse, within the last six months before randomization
  16. Screening total WBC count <3,000/μl, or platelets <100,000/μl or neutrophils <1,500/μl or hemoglobin <8.5 g/dl (85 g/L)
  17. History of clinically significant liver disease or liver injury indicated by abnormal liver function tests, such as SGOT (AST), SGPT (ALT), alkaline phosphatase and serum bilirubin. The investigator should be guided by the following criteria:

    • Any single parameter may not exceed 2 x the upper limit of normal (ULN). A single parameter elevated up to and including 2 x ULN should be re-checked once more as soon as possible, and in all cases, at least prior to randomization, to rule-out laboratory error.
    • If the total bilirubin concentration is increased above 2 x ULN, total bilirubin should be differentiated into the direct and indirect reacting bilirubin. In any case, serum bilirubin should not exceed the value of 1.6 mg/dL (27 µmol/L)
  18. Significant medical problems or diseases, including but not limited to the following:

    uncontrolled hypertension (≥160/95 mmHg), congestive heart failure (New York Heart Association status of class III or IV), uncontrolled diabetes, or very poor functional status precluding ability to perform self-care

  19. Plans for administration of live vaccines during the study period or within 6 weeks prior to randomization
  20. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during the entire study or longer if required by locally approved prescribing information (e.g., 20 weeks in EU). Effective contraception methods include:

    • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
    • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
    • Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject
    • Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps). For UK: with spermicidal foam/gel/film/cream/ vaginal suppository
    • Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception
    • Placement of an intrauterine device or intrauterine system In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.

    Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to randomization. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential.

  21. Active ongoing inflammatory diseases other than axSpA that might confound the evaluation of the benefits of secukinumab therapy, including inflammatory bowel disease or uveitis
  22. Current severe progressive or uncontrolled disease which in the judgment of the clinical investigator renders the subject unsuitable for the trial
  23. Use of other investigational drugs at the time of enrollment, or within 5 half- lives of enrollment, or within 4 weeks until the expected pharmacodynamic effect has returned to baseline, whichever is longer; or longer if required by local regulations
  24. History of hypersensitivity to any of the study drug constituents
  25. Previous exposure to secukinumab (AIN457) or any other biologic drug directly targeting IL-17 or the IL-17 receptor
  26. Previous treatment with any cell-depleting therapies including but not limited to anti-CD20 or investigational agents (e.g., CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04156620


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Alabama
Novartis Investigative Site Recruiting
Birmingham, Alabama, United States, 35205
United States, Arkansas
Novartis Investigative Site Recruiting
Jonesboro, Arkansas, United States, 72401
United States, California
Novartis Investigative Site Recruiting
La Mesa, California, United States, 91942
Novartis Investigative Site Recruiting
Upland, California, United States, 91786
United States, Colorado
Novartis Investigative Site Recruiting
Denver, Colorado, United States, 80230
United States, Maryland
Novartis Investigative Site Recruiting
Columbia, Maryland, United States, 21046
Novartis Investigative Site Recruiting
Hagerstown, Maryland, United States, 21740
United States, Nebraska
Novartis Investigative Site Recruiting
Lincoln, Nebraska, United States, 68516
United States, North Carolina
Novartis Investigative Site Recruiting
Greensboro, North Carolina, United States, 27408
United States, Pennsylvania
Novartis Investigative Site Recruiting
Duncansville, Pennsylvania, United States, 16635
United States, Washington
Novartis Investigative Site Recruiting
Spokane, Washington, United States, 99204
United States, West Virginia
Novartis Investigative Site Recruiting
Charleston, West Virginia, United States, 25304
Belgium
Novartis Investigative Site Recruiting
Bruxelles, Belgium, 1070
Novartis Investigative Site Recruiting
Leuven, Belgium, 3000
Sponsors and Collaborators
Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04156620    
Other Study ID Numbers: CAIN457P12301
First Posted: November 7, 2019    Key Record Dates
Last Update Posted: March 12, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Active axSpA, Axial spondyloarthritis, non-radiographic-axSpA, nr-axSpA, ankylosing spondylitis, AS, inflammatory back pain, sacroiliitis
Additional relevant MeSH terms:
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Spondylitis
Spondylitis, Ankylosing
Spondylarthritis
Bone Diseases, Infectious
Infection
Bone Diseases
Musculoskeletal Diseases
Spinal Diseases
Spondylarthropathies
Ankylosis
Joint Diseases
Arthritis