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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

28 Mar 2023 → ongoing

Decision date (initial)

2024-05-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-509320-17-00

EudraCT number

2022-001153-23

ClinicalTrials.gov

NCT05622708

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To evaluate whether continuous secukinumab treatment is superior to placebo in preventing flares during Treatment Period 2 in participants who achieved a state of remission in Treatment Period 1

Secondary objectives 2

1. To evaluate efficacy of secukinumab on preventing the onset of flares in participants in a state of remission during Treatment Period 2 in participants who achieved a state of remission in Treatment Period 1
2. To assess overall safety and tolerability of secukinumab over time up to follow-up visit

Conditions and MedDRA coding

non-radiographic axial spondyloarthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Male or non-pregnant, non-lactating female participants at least 18 years of age.
2. Clinical diagnosis of axSpA AND according to ASAS axSpA criteria: a. Inflammatory back pain for at least 6 months b. Onset before 45 years of age c. Sacroiliitis on MRI (as assessed by central reader) with ≥ 1 SpA feature OR HLA-B-27 positive with ≥2 SpA features
3. 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)
4. Active axSpA as assessed by total BASDAI ≥ 4 cm (0-10 cm) at baseline.
5. Spinal pain as measured by BASDAI question #2 ≥ 4 cm (0-10 cm) at baseline.
6. Total back pain as measured by VAS ≥ 40 mm (0-100 mm) at baseline.
7. 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 7

1. 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.
2. Participants taking high potency opioid analgesics (e.g., methadone, hydromorphone, morphine).
3. 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).
4. History of hypersensitivity to the study drug or its excipients or to drugs of similar chemical classes.
5. Active ongoing inflammatory diseases other than nr-axSpA that might confound the evaluation of the benefit of secukinumab therapy, including uveitis.
6. Active inflammatory bowel disease
7. History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of participants remaining flare-free at Week 120

Secondary endpoints 2

1. Time to flare during Treatment Period 2
2. Safety and tolerability demonstrated by assessing: • Adverse events (AEs) and serious adverse events (SAEs) (incidence, severity, and relationship with study drug) • Clinically significant changes in laboratory parameters and vital signs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 16

Locations

9 EU/EEA countries · 57 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 102 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications