Direct comparison between NSAIDs and biosimilar TNFa blockers in patients with axial spondyloarthritis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

St. Elisabeth Gruppe GmbH Katholische Kliniken Rhein-Ruhr

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

13 Mar 2025 → ongoing

Decision date (initial)

2024-12-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Celltrion Healthcare Deutschland GmbH

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To compare the potential to achieve low disease activity with repeated high-dose NSAID therapy with direct treatment with a TNF blocker in patients who have failed NSAID therapy in outpatient care.

Secondary objectives 1

1. To compare the effects of both treatment strategies on laboratory and MRI related inflammatory signs and other measures of disease activity and to evaluate intolerance and side effects observed in both treatment arms.

Conditions and MedDRA coding

Axial Spondyloarthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. A written informed consent form approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) has been signed by the patients.
2. Patients are at least 18 years of age at the time of the baseline visit.
3. Patients are considered reliable and are able to adhere to the protocol, comply with the schedule of visits, or take medications as judged by the investigator.
4. Diagnosis of r-axSpA by a rheumatologist.
5. Fulfilment of the ASAS classification criteria.
6. High disease activity status (ASDAS ≥2.1).
7. Positive MRI examination with inflammatory activity in the sacroiliac joint and/or the spine.
8. Patients must agree to the planned MRI procedures.
9. Patients must have failed NSAID therapy in outpatient care.
10. Patients must not have received pre -treatment b- and ts-DMARDs prior to the baseline visit ('bDMARD naïve').
11. Female patients of childbearing potential (FCBP) must use an effective method of contraception (including oral/parenteral/implantable hormonal contraceptives, intrauterine device or barrier, and spermicide or contraceptive methods considered at least as safe for contraception). FCBP must agree to use effective contraception during the study and for at least 6 months (according to the Summary of Product Characteristics) after the last dose of study treatment.
12. Male subjects who are not documented to be sterile must agree to ensure that they or their partner(s) use adequate contraception for the duration of the study.

Exclusion criteria 22

1. Patients have participated within the past 3 months or are currently participating in another study with an investigational drug (or medical device).
2. Patients who are unable to speak and read German .
3. Patients have a history of chronic alcohol or drug abuse.
4. Patients have a medical or psychiatric condition that, in the opinion of the investigator, would jeopardize or impair the ability to participate in this study.
5. Contraindication to TNF blocker or NSAID therapy.
6. Patients have a known hypersensitivity to any component of Remsima or the NSAIDs used in the study.
7. Pre-treatment with a b- or ts-DMARD.
8. Patients must not have any other inflammatory arthritis, e.g., RA, systemic lupus erythematosus, sarcoidosis, or others.
9. Patients must not have a secondary, non -inflammatory condition (e.g., osteoarthritis or fibromyalgia) that, in the opinion of the investigator, is sufficiently prominent to interfere with the evaluation of the effect of study drug on the primary diagnosis of axial SpA.
10. Female patients who are breastfeeding, pregnant, or plan to become pregnant during the study.
11. Patients who have received a live vaccination within the last 8 weeks prior to baseline.
12. Current malignancy or history of malignancy, although patients with less than 3 completely excised basal cell carcinomas or with one successfully operated cervical carcinoma in situ more than 5 years prior to baseline may be included.
13. Patients with severe, progressive, and/or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, or neurologic disease or with a history of such disease.
14. Patients with any other condition, including the presence of laboratory abnormalities, which, in the judgment of the investigator, makes the subject unsuitable for participation in the study.
15. Patients with any contraindication to perform MRI or failure to perform MRI prior to baseline.
16. Patients with clinically important active infections.
17. Female patients with positive urine pregnancy test.
18. Positive interferon gamma release assay (IGRA) test at screening and/or abnormal chest x -ray (within 3 months prior to baseline) suggestive for past or present tuberculosis.
19. Chronic infection such as hepatitis B or C infection.
20. Immunocompromised patients or history of HIV infection.
21. Patients who possibly are dependent on the Sponsor, the Principal Investigator or Investigator (e.g., family members).
22. Have participated in this study before

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Comparison of the proportion of patients on NSAID vs TNF blocker treatment who have low disease activity (ASDAS <2.1) after 12 weeks of treatment.

Secondary endpoints 12

1. Comparison of the proportion of patients on NSAID vs TNF blocker treatment who have low disease activity (ASDAS <2.1) after 4 and 24 weeks of treatment.
2. ASDAS-ID (inactive disease, ASDAS < 1.3), ASDAS -CII (clinically important improvement, Δ ≥ 1.1), ASDAS -MI (major improvement, Δ ≥ 2.0) after 4, 12 and 24 weeks.
3. ASAS-20, ASAS-40 at 4, 12 and 24 weeks.
4. BASDAI50 at weeks 4, 12 and 24 .
5. Change from baseline in Total Back Pain (PtBP), Patient Global Assessment (PtGA). Physician Global Assessment (PhGA) and other measures of disease activity (BASDAI), function (BASFI) at week 2, 4, 6, 12, 24, mobility (BASMI) and quality of life (ASAS Health Index) at week 4, 12, 24 .
6. Change from baseline in inflammatory activity in the MRI scan used for diagnosis at escalation and after 24 weeks.
7. Change from baseline in Epionics spine dimensions after 24 weeks .
8. Normalized net incremental area under the curve for ASDAS, Total Back Pain (PtBP), Patient Global Assessment (PtGA). Physician Global Assessment (PhGA) and other measures of disease activity (BASDAI), function (BASFI), mobility (BASMI, Epionics spine) and quality of life (ASAS Health Index).
9. Time to achieve ASDAS-LDA and time to ASDAS-ID.
10. Change from baseline in the laboratory examination (CRP) over the time of he examination period.
11. Comparison of the proportion of patients who discontinue therapy due to intolerance or side effects.
12. Incidence of adverse events and treatment emergent AEs and SAEs.

Investigational products

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

Test 2

Comparator 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

St. Elisabeth Gruppe GmbH Katholische Kliniken Rhein-Ruhr

Sponsor organisation

St. Elisabeth Gruppe GmbH Katholische Kliniken Rhein-Ruhr

Address

Hospitalstrasse 19, Wanne Wanne

City

Herne

Postcode

44649

Country

Germany

Scientific contact point

Organisation

St. Elisabeth Gruppe GmbH Katholische Kliniken Rhein-Ruhr

Contact name

Rheumazentrum Ruhrgebiet

Public contact point

Organisation

St. Elisabeth Gruppe GmbH Katholische Kliniken Rhein-Ruhr

Contact name

Rheumazentrum Ruhrgebiet

Third parties 1

Locations

1 EU/EEA country · 1 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 14 files

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

Application history

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