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

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

ClinicalTrials.gov Identifier: NCT04156620

Novartis Reference Number: CAIN457P12301

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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 
Ankylosing Spondylitis or Non-radiographic Axial Spondyloarthritis
Phase 
Phase 3
Overall status 
Recruiting
Enrollment count 
500 participants
Start date 
Dec 11, 2019
Completion date 
Feb 13, 2023
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

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)
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)

Eligibility Criteria

Inclusion Criteria:

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

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
Male and non-pregnant, non-lactating female patients ≥ 18 years of age

Diagnosis of axSpA according to ASAS criteria

Inflammatory back pain for at least 6 months
Onset before 45 years of age
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

For subjects with nr-axSpA:

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

Sacroiliitis on MRI (centrally read) with ≥ 1 SpA feature OR HLA-B-27 positive with ≥2 SpA features AND
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)
Active axial SpA assessed by BASDAI ≥4 cm (0-10 cm) at Baseline
Spinal pain as measured by BASDAI question #2 ≥ 4 cm (0-10 cm) at Baseline
Total back pain as measured by VAS ≥ 40 mm (0-100 mm) at Baseline
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
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

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

4 weeks for Enbrel® (etanercept) - with a terminal half-life of 102 ± 30 hours
8 weeks for Remicade® (infliximab) - with a terminal half-life of 8.0-9.5 days
10 weeks for Humira® (adalimumab) - with a terminal half-life of 10-20 days (average 2 weeks)
10 weeks for Simponi® (golimumab) - with a terminal half-life of 11-14 days
10 weeks for Cimzia® (certolizumab) - with a terminal half-life of 14 days
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
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
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

Subjects with total ankylosis of the spine
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
Subjects taking moderate and high potency opioid analgesics (e.g. methadone, hydromorphone, morphine)
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)
Any therapy by intra-articular injections (e.g. corticosteroid) within 4 weeks before Randomization
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
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
Active systemic infections during the last two weeks (exception: common cold) prior to randomization or any infection that reoccurs on a regular basis
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
Past medical history of infection with HIV or hepatitis B prior to randomization or active infection or on treatment for Hepatitis C at randomization
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)
Use or planned use of prohibited concomitant medication (see Section 6.2.2)
Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor tolerability or lack of access to veins)
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
History or evidence of ongoing alcohol or drug abuse, within the last six months before randomization
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)

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)

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

Plans for administration of live vaccines during the study period or within 6 weeks prior to randomization

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.

Active ongoing inflammatory diseases other than axSpA that might confound the evaluation of the benefits of secukinumab therapy, including inflammatory bowel disease or uveitis
Current severe progressive or uncontrolled disease which in the judgment of the clinical investigator renders the subject unsuitable for the trial
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
History of hypersensitivity to any of the study drug constituents
Previous exposure to secukinumab (AIN457) or any other biologic drug directly targeting IL-17 or the IL-17 receptor
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)

Study Locations

United States
Novartis Investigative Site
Recruiting
Birmingham, 35205
Alabama
United States
Novartis Investigative Site
Recruiting
Jonesboro, 72401
Arkansas
United States
Novartis Investigative Site
Recruiting
La Mesa, 91942
California
United States
Novartis Investigative Site
Recruiting
San Leandro, 94578
California
United States
Novartis Investigative Site
Recruiting
Upland, 91786
California
United States
Novartis Investigative Site
Recruiting
Denver, 80230
Colorado
United States
Novartis Investigative Site
Recruiting
Ocoee, 34761
Florida
United States
Novartis Investigative Site
Recruiting
Plantation, 33324
Florida
United States
Novartis Investigative Site
Recruiting
Winter Park, 32789
Florida
United States
Novartis Investigative Site
Recruiting
Bowling Green, 42101
Kentucky
United States
Novartis Investigative Site
Recruiting
Columbia, 21046
Maryland
United States
Novartis Investigative Site
Recruiting
Cumberland, 21740
Maryland
United States
Novartis Investigative Site
Recruiting
Lansing, 48910
Michigan
United States
Novartis Investigative Site
Recruiting
Lincoln, 68516
Nebraska
United States
Novartis Investigative Site
Recruiting
Greensboro, 27408
North Carolina
United States
Novartis Investigative Site
Recruiting
Middleburg Heights, 44130
Ohio
United States
Novartis Investigative Site
Recruiting
Duncansville, 16635
Pennsylvania
United States
Novartis Investigative Site
Recruiting
Jackson, 38305
Tennessee
United States
Novartis Investigative Site
Recruiting
College Station, 77845
Texas
United States
Novartis Investigative Site
Recruiting
Spokane, 99204
Washington
United States
Novartis Investigative Site
Recruiting
Charleston, 25304
West Virginia
United States
Belgium
Novartis Investigative Site
Recruiting
Bruxelles, 1070
-
Belgium
Novartis Investigative Site
Recruiting
Leuven, 3000
-
Belgium
Brazil
Novartis Investigative Site
Recruiting
Salvador, 40150 150
BA
Brazil
Novartis Investigative Site
Recruiting
Vitoria, 29055 450
ES
Brazil
Novartis Investigative Site
Recruiting
Juiz de Fora, 36010 570
MG
Brazil
Novartis Investigative Site
Recruiting
São Paulo, 01244-030
SP
Brazil
Novartis Investigative Site
Recruiting
Rio de Janeiro, 20241-180
-
Brazil
Novartis Investigative Site
Recruiting
Sao Jose do Rio Preto, 15090 000
-
Brazil
Bulgaria
Novartis Investigative Site
Recruiting
Pleven, 5800
-
Bulgaria
Novartis Investigative Site
Recruiting
Plovdiv, 4000
-
Bulgaria
Novartis Investigative Site
Recruiting
Plovdiv, 4002
-
Bulgaria
Novartis Investigative Site
Recruiting
Sofia, 1413
-
Bulgaria
Novartis Investigative Site
Recruiting
Sofia, 1431
-
Bulgaria
Colombia
Novartis Investigative Site
Recruiting
Bucaramanga, 0001
Santander
Colombia
Czechia
Novartis Investigative Site
Recruiting
Ostrava, 772 00
Czech Republic
Czechia
Novartis Investigative Site
Recruiting
Praha 2, 128 50
-
Czechia
Novartis Investigative Site
Recruiting
Praha 4, 140 59
-
Czechia
Novartis Investigative Site
Recruiting
Praha 5, 150 06
-
Czechia
Novartis Investigative Site
Recruiting
Uherske Hradiste, 686 01
-
Czechia
Greece
Novartis Investigative Site
Recruiting
Patra, 26443
-
Greece
Guatemala
Novartis Investigative Site
Recruiting
Guatemala, 01010
-
Guatemala
India
Novartis Investigative Site
Recruiting
Ahmedabad, 380015
Gujarat
India
Novartis Investigative Site
Recruiting
Nashik, 422 101
Maharashtra
India
Italy
Novartis Investigative Site
Recruiting
Verona, 37134
VR
Italy
Korea, Republic of
Novartis Investigative Site
Recruiting
Gwangju, 61469
-
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 04763
-
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 05278
-
Korea, Republic of
Malaysia
Novartis Investigative Site
Recruiting
Seremban, 70300
Negeri Sembilan
Malaysia
Novartis Investigative Site
Recruiting
Ipoh, 30450
Perak
Malaysia
Novartis Investigative Site
Recruiting
Kuching, 93586
Sarawak
Malaysia
Novartis Investigative Site
Recruiting
Kuala Lumpur, 59100
-
Malaysia
Novartis Investigative Site
Recruiting
Selangor Darul Ehsan, 68100
-
Malaysia
Philippines
Novartis Investigative Site
Recruiting
Quezon City, 1102
-
Philippines
Poland
Novartis Investigative Site
Recruiting
Bialystok, 15-351
-
Poland
Novartis Investigative Site
Recruiting
Sochaczew, 96-500
-
Poland
Novartis Investigative Site
Recruiting
Torun, 87-100
-
Poland
Russian Federation
Novartis Investigative Site
Recruiting
Kazan, 420064
-
Russian Federation
Novartis Investigative Site
Recruiting
Kemerovo, 650029
-
Russian Federation
Novartis Investigative Site
Recruiting
Kemerovo, 650070
-
Russian Federation
Novartis Investigative Site
Recruiting
Novosibirsk, 630047
-
Russian Federation
Novartis Investigative Site
Recruiting
Novosibirsk, 630099
-
Russian Federation
Novartis Investigative Site
Recruiting
Petrozavodsk, 185019
-
Russian Federation
Novartis Investigative Site
Recruiting
St Petersburg, 190068
-
Russian Federation
Novartis Investigative Site
Recruiting
Ulyanovsk, 432063
-
Russian Federation
Novartis Investigative Site
Recruiting
Yaroslavl, 150003
-
Russian Federation
Thailand
Novartis Investigative Site
Recruiting
Bangkoknoi, 10700
Bangkok
Thailand
Novartis Investigative Site
Recruiting
Bangkok, 10400
-
Thailand
Turkey
Novartis Investigative Site
Recruiting
Ankara, 06100
-
Turkey
Novartis Investigative Site
Recruiting
Edirne, 22030
-
Turkey

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
1-888-669-6682
Name: 
Novartis Pharmaceuticals
Phone: 
+41613241111
Email: 

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