A Study of Secukinumab to Evaluate Maintenance of Response in Participants With Non-radiographic Axial Spondyloarthritis Who Achieved Remission

Non-radiographic Axial Spondyloarthritis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05622708
• Other study ID #: CAIN457I2401
• Secondary ID: 2022-001153-23
• Status: Recruiting
• Phase: Phase 4
• Start date: March 28, 2023
• Est. completion date: June 19, 2030

Study information

• Verified date: May 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: +41613241111
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 340
• Est. completion date: June 19, 2030
• Est. primary completion date: April 24, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 TNFa (tumor necrosis factor a) (unless participants discontinued the treatment with TNFa 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.

Related Conditions & MeSH terms

• Axial Spondyloarthritis
• Non-Radiographic Axial Spondyloarthritis
• Spondylarthritis
• Spondylitis

Intervention

Drug:
• Secukinumab
Treatment Period 1: Open-label secukinumab 150 mg PFS s.c. at baseline, Weeks 1, 2, 3 and 4 followed by administration every four weeks up to Week 52.
• Placebo
Treatment Period 2: Double-blind placebo PFS s.c. every 4 weeks from Week 56 to Week 116.
• Secukinumab
Treatment Period 2: Double-blind secukinumab 150 mg PFS s.c. every 4 weeks from Week 56 to Week 116. Escape re-treatment (during Treatment Period 2): Open-label secukinumab 150 mg PFS s.c.

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Brugge
Belgium	Novartis Investigative Site	Genk
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative Site	Mons
Brazil	Novartis Investigative Site	Barretos	Sao Paulo
Brazil	Novartis Investigative Site	Juiz de Fora	MG
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Sao Paulo
Colombia	Novartis Investigative Site	Barranquilla
Colombia	Novartis Investigative Site	Bogota
Colombia	Novartis Investigative Site	Bogota	Cundinamarca
Colombia	Novartis Investigative Site	Bucaramanga	Santander
Colombia	Novartis Investigative Site	Cundinamarca
Czechia	Novartis Investigative Site	Plzen Bory
Czechia	Novartis Investigative Site	Praha 11
Czechia	Novartis Investigative Site	Praha 2
Czechia	Novartis Investigative Site	Praha 5
Czechia	Novartis Investigative Site	Uherske Hradiste
France	Novartis Investigative Site	Chambray les Tours
France	Novartis Investigative Site	Le Mans
France	Novartis Investigative Site	Nice	Cedex1
France	Novartis Investigative Site	Orleans	Cedex 2
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Toulouse Cedex 9
Germany	Novartis Investigative Site	Bad Doberan
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Herne
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Ratingen
Germany	Novartis Investigative Site	Rendsburg
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Eger
Hungary	Novartis Investigative Site	Kistarcsa
Hungary	Novartis Investigative Site	Miskolc
Hungary	Novartis Investigative Site	Szeged
Hungary	Novartis Investigative Site	Szekesfehervar	Fejer
Hungary	Novartis Investigative Site	Veszprem
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Kfar Saba
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Tel Aviv
Italy	Novartis Investigative Site	Ancona	AN
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Negrar	VR
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Torino	TO
Italy	Novartis Investigative Site	Verona	VR
Malaysia	Novartis Investigative Site	Kuala Lumpur
Malaysia	Novartis Investigative Site	Kuching	Sarawak
Malaysia	Novartis Investigative Site	Selangor Darul Ehsan
Mexico	Novartis Investigative Site	Chihuahua
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Merida	Yucatan
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Heerlen
Netherlands	Novartis Investigative Site	Maastricht
Philippines	Novartis Investigative Site	Makati	Metro Manila
Philippines	Novartis Investigative Site	Manila
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Bydgoszcz
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Krakow	Malopolskie
Poland	Novartis Investigative Site	Sochaczew
Poland	Novartis Investigative Site	Torun
Poland	Novartis Investigative Site	Warszawa
Romania	Novartis Investigative Site	Brasov
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Bucuresti
Romania	Novartis Investigative Site	Cluj Napoca
Romania	Novartis Investigative Site	Sibiu
Romania	Novartis Investigative Site	Suceava
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Turkey	Novartis Investigative Site	Adana
Turkey	Novartis Investigative Site	Konya
Turkey	Novartis Investigative Site	Pendik	Istanbul
Vietnam	Novartis Investigative Site	Ho Chi Minh	VNM
Vietnam	Novartis Investigative Site	Ho Chi Minh

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Belgium,  Brazil,  Colombia,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Malaysia,  Mexico,  Netherlands,  Philippines,  Poland,  Romania,  Thailand,  Turkey,  Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportion of participants remaining flare-free during Treatment Period 2	The primary efficacy endpoint is the proportion of participants in the randomized withdrawal population remaining flare-free at Week 120. A flare is defined as ASDAS-CRP = 2.1 at 2 consecutive visits, or ASDAS-CRP > 3.5 at any visit during Treatment Period 2, starting at Week 60.; Parameters used for ASDAS-CRP include: Spinal pain (BASDAI question 2),; Patient's global assessment of disease activity,; Peripheral pain/swelling (BASDAI question 3),; Duration of morning stiffness (BASDAI question 6); C-reactive protein (CRP) in mg/L	Week 120
Secondary	Time to flare during Treatment Period 2	A flare is defined as ASDAS-CRP = 2.1 at 2 consecutive visits, or ASDAS-CRP > 3.5 at any visit during Treatment Period 2, starting at Week 60.	From Week 56 to Week 120
Secondary	Number of participants with Adverse Events	Safety and tolerability demonstrated by assessing: - Adverse events (AEs) and serious adverse events (SAEs)	From Baseline to Week 128