Clinical study to examine the clinical efficacy and the NSAID-sparing effect of Secukinumab in patients with ankylosing spondylitis

• Register: EUCTR
• Last refreshed on: 16 December 2019
• Main ID: EUCTR2015-004575-74-DE
• Date of registration: 18/02/2016
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma GmbH
• Public title: Clinical study to examine the clinical efficacy and the NSAID-sparing effect of Secukinumab in patients with ankylosing spondylitis
• Scientific title: A randomized, double-blind, placebo-controlled multicenter study of Secukinumab (AIN457) to examine the clinical efficacy and the NSAID-sparing effect of Secukinumab over 16 weeks in patients with ankylosing spondylitis (ASTRUM) - ASTRUM
• Date of first enrolment: 16/03/2016
• Target sample size: 190
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004575-74
• 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: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Germany

Contacts

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patient must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study assessment is performed
2. Male or non-pregnant, non-lactating female patients at least 18 years of age
3. Diagnosis of active AS with prior documented radiologic evidence (X-ray or radiologist’s report) fulfilling the Modified New York criteria for AS (Appendix 3)
4. Active AS assessed by total BASDAI = 4 (0-10) at baseline
5. Spinal pain as measured by BASDAI Question 2 = 4 cm on a 0-10 cm numeric rating scale at baseline
6. Total back pain as measured by VAS = 40 mm (0-100 mm) at baseline
7. Patients should have been on at least 2 different NSAIDs at the highest recommended dose for at least 4 weeks in total in the past, prior to randomization, with an inadequate response or failure to respond, or less if therapy had to be reduced due to intolerance, toxicity or contraindications
8. Patients must report regular intake of NSAIDs of at least 50% of the highest recommended dose at Screening. Patients with prior TNFa inhibitor therapy must report regular intake of NSAIDs of at least 50% of the highest recommended dose at baseline after the appropriate washout
9. Patients are required to be on a stable dose of NSAIDs for at least 2 weeks before randomization
10. Patients who have previously been on a TNFa inhibitor will be allowed entry into study after an appropriate wash-out period prior to randomization:
• 4 weeks for Enbrel® (etanercept) – with a terminal half-life of 102 ± 30 hours (s.c. route)
• 8 weeks for Remicade® (infliximab) – with a terminal half-life of 8.0-9.5 days (i.v. infusion)
• 10 weeks for Humira® (adalimumab) – with a terminal half-life of 10-20 days (average 2 weeks) (s.c. route)
• 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
11. Patients who have been on a TNFa inhibitor (not more than two) must have experienced an inadequate response to previous or current treatment given at an approved dose for at least 3 months prior to randomization or have been intolerant to at least one administration of an anti-TNFa agent. No more than 40% of patients may have previously received anti-TNFa agents
12. Patients taking 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 be on a stable dose for at least 4 weeks prior to randomization
13. Patients on MTX must be on stable folic acid supplementation before randomization
14. Patients who are on a DMARD other than MTX or sulfasalazine must discontinue the DMARD 4 weeks prior to randomization, except for leflunomide, which has to be discontinued for 8 weeks prior to randomization unless a cholestyramine washout has been performed
15. Patients taking systemic corticosteroids have to be on a stable dose of = 10 mg/day prednisone or equivalent for at least 2 weeks before randomization

Are the trial subjects under 18? no
Number of subj
Exclusion criteria:
1. 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
2. Patients taking high potency opioid analgesics
3. Previous exposure to Secukinumab or any other biologic drug directly targeting IL-17 or IL-17 receptor
4. Use of any investigational drug and/or devices within 4 weeks of randomization, or a period of 5 half-lives of the investigational drug, whichever is longer or participation in another clinical study (interventional or non-interventional) in the same indication during enrollment in this study
5. History of hypersensitivity to the study drug or its excipients or to drugs of similar chemical classes
6. Any therapy by intra-articular injections within 4 weeks before randomization
7. Any intramuscular corticosteroid injection within 2 weeks before randomization
8. Patients previously treated with any biological immunomodulating agents, except those targeting TNFa
9. Patients who have taken more than two anti-TNFa agents
10. Previous treatment with any cell-depleting therapies including but not limited to anti-CD20 or investigational agents 11. 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 human chorionic gonadotropin laboratory test
12. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during entire study or longer if required by locally approved prescribing information.
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 ago. 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 child bearing potential.
13. Active ongoing inflammatory diseases other than AS that might confound the evaluation of the benefit of Secukinumab therapy, including inflammatory bowel disease or uveitis
14. Underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions, which in the opinion of the investigator immunocompromises the patient and/or places the patient at unacceptable risk for participation in an immunomodulatory therapy
15. 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 unable to perform self-care
16. History of clinically significant liver disease or liver injury as indicated by abnormal liver function tests suc

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

Health Condition(s) or Problem(s) studied

Ankylosing Spondylitis
MedDRA version: 20.0 Level: PT Classification code 10002556 Term: Ankylosing spondylitis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Trade Name: Cosentyx
Product Name: Secukinumab
Product Code: AIN457
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: SECUKINUMAB
CAS Number: 1229022-83-6
Current Sponsor code: AIN457
Other descriptive name: SECUKINUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
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 demonstrate that the efficacy of Secukinumab 150 mg s.c. (with NSAID tapering) is superior to placebo based on the proportion of patients achieving an ASAS20 response at week 12. To show superiority, both Secukinumab treatment arms will be pooled and compared against placebo.

Timepoint(s) of evaluation of this end point: at week 12

Secondary Objective: • change from baseline in ASAS-NSAID score and in total BASDAI at week 12 is superior for Secukinumab 150 mg compared to placebo. Both Secukinumab treatment arms will be pooled.
• efficacy of Secukinumab 150 mg at Week 12 (early and delayed NSAID tapering) and Week 16 (early NSAID tapering) is superior to placebo based on proportion of patients achieving ASAS20 response.
• change from baseline in ASAS-NSAID score at Week 12 is superior for Secukinumab 150 mg (early and delayed NSAID tapering) as compared to placebo.
• efficacy of Secukinumab 150 mg at Week 12 (early and delayed NSAID tapering) and week 16 (early NSAID tapering) is superior to placebo based on change from baseline in total BASDAI.
• efficacy of Secukinumab 150 mg (early and delayed NSAID tapering) at Week 12 is superior to placebo based on change from baseline in health-related QoL as measured by SF-36 PCS.
• compare both Secukinumab regimens concerning change from baseline in ASAS-NSAID score after 12 weeks.

Primary end point(s): To demonstrate that the efficacy of Secukinumab 150 mg s.c. (with NSAID tapering) is superior to placebo based on the proportion of patients achieving an ASAS20 response at week 12. To show superiority, both Secukinumab treatment arms will be pooled and compared against placebo.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: at week 12 and week 16

Secondary end point(s): 1. To demonstrate that the change from baseline in ASAS-NSAID score at week 12 is superior for Secukinumab 150 mg s.c. as compared to placebo. To show superiority, both Secukinumab treatment arms will be pooled and compared against placebo.
2. To demonstrate that the efficacy of Secukinumab 150 mg s.c at week 12 is superior to placebo based on the change from baseline in the total BASDAI. To show superiority, both Secukinumab treatment arms will be pooled and compared against placebo.
3. To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 0 with NSAID tapering allowed from week 4; “delayed tapering”) at Week 12 is superior to placebo based on the proportion of patients achieving an ASAS20 response.
4. To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 4 with NSAID tapering allowed from week 4; “early tapering”) at Week 12 is superior to placebo based on the proportion of patients achieving an ASAS20 response.
5. To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 4 with NSAID tapering allowed from week 4; “early tapering”) at Week 16 is superior to placebo based on the proportion of patients achieving an ASAS20 response.
6. To demonstrate that the change from baseline in ASAS-NSAID score at Week 12 is superior for Secukinumab 150 mg s.c. (Secukinumab from week 0 with NSAID tapering allowed from week 4; “delayed tapering”) as compared to placebo.
7. To demonstrate that the change from baseline in ASAS-NSAID score at Week 12 is superior for Secukinumab 150 mg s.c . (Secukinumab from week 4 with NSAID tapering allowed from week 4; “early tapering”) as compared to placebo.
8. To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 0 with NSAID tapering allowed from week 4; “delayed tapering”) at Week 12 is superior to placebo based on the change from baseline in the total BASDAI.
9. To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 4 with NSAID tapering allowed from week 4; “early tapering”) at Week 12 is superior to placebo based on the change from baseline in the total BASDAI.
10. To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 4 with NSAID tapering allowed from week 4; “early tapering”) at Week 16 is superior to placebo based on the change from baseline in the total BASDAI.
11. To demonstrate that the efficacy of Secukinumab 150 mg s.c. at week 12 is superior to placebo based on the change from baseline in health-related Quality of Life as measured by the SF-36 PCS.
12. To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 0 with NSAID tapering allowed from week 4; “delayed tapering”) at Week 12 is superior to placebo based on the change from baseline in health-related Quality of Life as measured by the SF-36 PCS.
13. To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 4 with NSAID tapering allowed from week 4; “early tapering”) at Week 12 is superior to placebo based on the change from baseline in health-related Quality of Life as measured by the SF-36 PCS.
14. To compare between both Secukinumab regimens concerning the change from baseline in ASAS-NSAID score after 12 weeks of Secukinumab exposure (ASAS-NSAID index at Week 12 for “delayed tapering” vs. Week 16 for “early tapering”).

Secondary ID(s)

CAIN457FDE03

Source(s) of Monetary Support

Novartis Pharma GmbH

Ethics review

Status: Approved
Approval date:
Contact: