Clinical trial NCT05622708: A Study of Secukinumab to Evaluate Maintenance of Response in Participants With Non-radiographic Axial Spondyloarthritis Who Achieved Remission
Official title: A Multicenter Study of Secukinumab, With a Randomized Double-blind, Placebo-controlled Withdrawal-retreatment Period, to Evaluate Maintenance of Response in Participants With Non-radiographic Axial Spondyloarthritis Who Achieved Remission
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Non-radiographic Axial Spondyloarthritis
Keywords: nr-AxSpa
non-radiographic axial Spondyloarthritis
Secukinumab
remission
withdrawal
inflammatory back pain
sacroiliitis
AIN457
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-11-21
Enrollment: 340
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This phase IV, multicenter study uses a double-blind, placebo-controlled, randomized withdrawal design (Treatment Period 2) preceded by an open label lead-in period (Treatment Period 1).
Primary purpose: TREATMENT

Brief summary: This study will establish whether prolonged chronic dosing with secukinumab is needed in participants with Non-radiographic axial spondyloarthritis, (nr-axSpA) who have achieved remission. Remission is defined as Ankylosing Spondylitis Disease Activity Score - C-reactive protein (ASDAS-CRP) Inactive Disease (ID) response (ASDAS-CRP \< 1.3). Maintenance of remission on continued secukinumab treatment will be evaluated compared to placebo using a randomized withdrawal design. The primary outcome measure for this study is the proportion of participants remaining flare-free at Week 120.

Detailed description: This study will establish whether prolonged chronic dosing with secukinumab is needed in participants with nr-axSpA who have achieved remission. Remission is defined as Ankylosing Spondylitis Disease Activity Score - C-reactive protein (ASDAS-CRP) Inactive Disease (ID) response Inactive Disease (ID) response (ASDAS-CRP \< 1.3). The maintenance of remission on continued secukinumab treatment will be evaluated compared to placebo using a randomized withdrawal design. The primary outcome measure for this study is the proportion of participants remaining flare-free at Week 120.

Study treatment will be as follows:

* Open-label Secukinumab PFS (prefilled syringe) will be labeled as AIN457 150mg/1mL
* Double-blind Secukinumab and Placebo PFS will be labeled as AIN457 150mg/1mL/Placebo.

Study duration will be up to 128 weeks from Baseline.

The treatment duration will be up to 120 weeks with last treatment administration at Week 116.

In the Treatment Period 1 participant will attend a site visit approximately 1 month after Baseline and approximately every 12 weeks thereafter. In the Treatment Period 2 participant will attend site visits approximately every 4 weeks.

Eligibility criteria: Inclusion Criteria:

* Male or non-pregnant, non-lactating female participants at least 18 years of age
* Clinical diagnosis of axSpA AND according to ASAS axSpA criteria:

  1. Inflammatory back pain for at least 6 months
  2. Onset before 45 years of age
  3. Sacroiliitis on MRI (magnetic resonance imaging) (as assessed by central reader) with ≥ 1 SpA feature OR HLA-B-27 positive with ≥2 SpA features
* Objective signs of inflammation at screening, evident by either MRI with Sacroiliac Joint inflammation (as assessed by central reader) AND / OR hsCRP \> ULN (as defined by the central lab)
* Active axSpA as assessed by total 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 (visual analog scale) ≥ 40 mm (0-100 mm) at baseline.
* Participants should have been on at least 2 different NSAIDs (non-steroidal anti-inflammatory drugs) at the highest recommended dose for at least 4 weeks in total prior to baseline with an inadequate response or failure to respond, or less if therapy had to be withdrawn due to intolerance, toxicity or contraindications.

Exclusion Criteria:

* Participants with radiographic evidence for sacroiliitis, grade ≥ 2 bilaterally or grade ≥ 3 unilaterally (radiological criterion according to the modified New York diagnostic criteria for AS) as assessed by central reader.
* Participants taking high potency opioid analgesics (e.g., methadone, hydromorphone, morphine).
* Previous exposure to secukinumab or any other biologic drug directly targeting IL-17 or IL-17 receptor or previous treatment with immunomodulatory biologic agents including those targeting TNFα (tumor necrosis factor α) (unless participants discontinued the treatment with TNFα inhibitor due to a reason other than efficacy \[primary or secondary lack of efficacy, inadequate response\] and only after appropriate wash-out period prior to baseline was observed).
* History of hypersensitivity to the study drug or its excipients or to drugs of similar chemical classes.
* Active ongoing inflammatory diseases other than nr-axSpA that might confound the evaluation of the benefit of secukinumab therapy, including uveitis.
* Active inflammatory bowel disease.
* History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection.

Primary outcomes:
measure: The proportion of participants remaining flare-free during Treatment Period 2
timeFrame: Week 120
Secondary outcomes:
measure: Time to flare during Treatment Period 2
timeFrame: From Week 56 to Week 120
measure: Number of participants with Adverse Events
timeFrame: From Baseline to Week 128
Other outcomes:
Locations:
city: Brugge
country: Belgium
facility: Novartis Investigative Site
city: Genk
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Mons
country: Belgium
facility: Novartis Investigative Site
city: Juiz de Fora
country: Brazil
facility: Novartis Investigative Site
state: MG
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Barretos
country: Brazil
facility: Novartis Investigative Site
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
city: Bogota
country: Colombia
facility: Novartis Investigative Site
state: Cundinamarca
city: Chia
country: Colombia
facility: Novartis Investigative Site
state: Cundinamarca
city: Bucaramanga
country: Colombia
facility: Novartis Investigative Site
state: Santander
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
city: Bogota
country: Colombia
facility: Novartis Investigative Site
city: Plzen Bory
country: Czechia
facility: Novartis Investigative Site
city: Praha 11
country: Czechia
facility: Novartis Investigative Site
city: Praha 2
country: Czechia
facility: Novartis Investigative Site
city: Praha 5
country: Czechia
facility: Novartis Investigative Site
city: Uherske Hradiste
country: Czechia
facility: Novartis Investigative Site
city: Chambray les Tours
country: France
facility: Novartis Investigative Site
city: Le Mans
country: France
facility: Novartis Investigative Site
city: Nice
country: France
facility: Novartis Investigative Site
city: Orleans
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Toulouse Cedex 9
country: France
facility: Novartis Investigative Site
city: Bad Doberan
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Herne
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Ratingen
country: Germany
facility: Novartis Investigative Site
city: Rendsburg
country: Germany
facility: Novartis Investigative Site
city: Szekesfehervar
country: Hungary
facility: Novartis Investigative Site
state: Fejer
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Eger
country: Hungary
facility: Novartis Investigative Site
city: Kistarcsa
country: Hungary
facility: Novartis Investigative Site
city: Miskolc
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: Veszprem
country: Hungary
facility: Novartis Investigative Site
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Kfar Saba
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Negrar
country: Italy
facility: Novartis Investigative Site
state: VR
city: Verona
country: Italy
facility: Novartis Investigative Site
state: VR
city: Kuching
country: Malaysia
facility: Novartis Investigative Site
state: Sarawak
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
city: Selangor Darul Ehsan
country: Malaysia
facility: Novartis Investigative Site
city: Guadalajara
country: Mexico
facility: Novartis Investigative Site
state: Jalisco
city: Guadalajara
country: Mexico
facility: Novartis Investigative Site
state: Jalisco
city: Merida
country: Mexico
facility: Novartis Investigative Site
state: Yucatan
city: Chihuahua
country: Mexico
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Heerlen
country: Netherlands
facility: Novartis Investigative Site
city: Maastricht
country: Netherlands
facility: Novartis Investigative Site
city: Makati
country: Philippines
facility: Novartis Investigative Site
state: Metro Manila
city: Manila
country: Philippines
facility: Novartis Investigative Site
city: Krakow
country: Poland
facility: Novartis Investigative Site
state: Malopolskie
city: Bialystok
country: Poland
facility: Novartis Investigative Site
city: Bydgoszcz
country: Poland
facility: Novartis Investigative Site
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Sochaczew
country: Poland
facility: Novartis Investigative Site
city: Torun
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Brasov
country: Romania
facility: Novartis Investigative Site
city: Bucharest
country: Romania
facility: Novartis Investigative Site
city: Bucuresti
country: Romania
facility: Novartis Investigative Site
city: Cluj Napoca
country: Romania
facility: Novartis Investigative Site
city: Sibiu
country: Romania
facility: Novartis Investigative Site
city: Suceava
country: Romania
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Adana
country: Turkey
facility: Novartis Investigative Site
city: Konya
country: Turkey
facility: Novartis Investigative Site
city: Pendik Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Ho Chi Minh
country: Vietnam
facility: Novartis Investigative Site
state: VNM
city: Ho Chi Minh
country: Vietnam
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: