Evaluation of upadacitinib in adult subjects with axial spondyloarthritis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Abbvie Deutschland GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

23 Mar 2020 → 28 Feb 2025

Decision date (initial)

2022-12-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AbbVie Inc.

External identifiers

EU CT number

2022-501018-78-00

EudraCT number

2019-003229-12

ClinicalTrials.gov

NCT04169373

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Pharmacokinetic, Pharmacogenetic, Efficacy, Pharmacogenomic

• To evaluate the efficacy of upadacitinib compared with placebo on reduction of signs and symptoms in adult subjects with active axSpA including bDMARD-IR AS (Study 1) and nr-axSpA (Study 2);
• To assess the safety and tolerability of upadacitinib in subjects with active axSpA including bDMARD-IR AS (Study 1) and with nr-axSpA (Study 2).

Secondary objectives 2

1. To evaluate the safety and tolerability of upadacitinib in extended treatment in adult subjects with active axSpA including bDMARD-IR AS who have completed the Double-Blind Period (Study 1) and with nr-axSpA who have completed the Double-Blind Period (Study 2)
2. To evaluate the maintenance of disease control after withdrawal of upadacitinib in those who achieved ASDAS < 1.3 at Week 104 and ASDAS < 2.1 at Week 88.

Conditions and MedDRA coding

Axial Spondyloarthritis

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Adult females and males who are at least 18 years of age
2. Study 1: Clinical diagnosis of AS who meet the modified New York Criteria for AS
3. Study 1: Subjects must have been exposed to 1 or 2 bDMARDs (at least 1 tumor necrosis factor (TNF) inhibitor or 1 interleukin [IL]-17 inhibitor) and subject must have discontinued bDMARD therapy due to either lack of efficacy (after at least 12 weeks of treatment with a bDMARD at an adequate dose) or intolerance (irrespective of treatment duration). Prior exposure to a 2nd bDMARD is allowed for no more than 30% of subjects. Subjects who have had lack of efficacy to 2 bDMARDs (including both a TNF-inhibitor and IL-17 inhibitor) are not eligible.
4. Study 2: Clinical diagnosis of nr-axSpA fulfilling the 2009 ASAS classification criteria for axSpA but not meeting the radiologic criterion of the modified New York criteria for AS and have objective signs of active inflammation on MRI of sacroiliac joints or based on high sensitivity CRP > ULN.
5. Study 2: Prior treatment with at most 1 bDMARD (either 1 TNF inhibitor or 1 IL-17 inhibitor) is allowed in at least 20%, but not exceeding 35% of subjects.
6. Must have a BASDAI score ≥ 4 and a Patient's Assessment of Total Back Pain score ≥ 4 based on a 0 – 10 numerical rating scale at the Screening and Baseline Visits.
7. Remission-Withdrawal Period: Subject must be on study drug upon completion of the Open-Label Extension Period of Study 1 or Study 2 through Week 104.
8. Remission-Withdrawal Period: Subject must achieve ASDAS (CRP) < 1.3 at Week 104 and ASDAS (CRP) < 2.1 at Week 88.
9. Remission-Withdrawal Period: Subject must not have a newly suspected/acquired medical condition and/or initiate a new medication since the last dose of study drug that would have precluded his/her enrollment into the main study.
10. Remission-Withdrawal Period: There must be no reason the Investigator believes that the subject is an unsuitable candidate to participate in the remission-withdrawal period or receive study drug or would place the subjects at risk by continuing to participate in the study.
11. Remission-Withdrawal Period: Subjects must be willing to keep background axSpA medications stable during the Remission-Withdrawal Period.
12. Subject must be able to understand and willing to adhere to all protocol requirements and voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/institutional review board (IRB), prior to the initiation of any screening or study-specific procedures.

Exclusion criteria 2

1. Subject must not have total spinal ankylosis
2. Subjects who have had an inadequate response to both a TNF inhibitor and IL-17 inhibitor are not eligible.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Study 1 - Primary endpoint is ASAS 40 response at week 14
2. Study 2 - Primary endpoint is ASAS 40 response at week 14

Secondary endpoints 29

1. Study 1: Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS)
2. Study 1: Change from Baseline in magnetic resonance imaging (MRI) Spondyloarthritis Research Consortium of Canada (SPARCC) score (spine)
3. Study 1: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 response
4. Study 1: ASAS20 response
5. Study 1: ASDAS Inactive Disease (ASDAS score < 1.3)
6. Study 1: Change from Baseline in Patient's Assessment of Total Back Pain (Total Back Pain)
7. Study 1: Change from Baseline in Patient's Assessment of Nocturnal Back Pain (Nocturnal Back Pain)
8. Study 1: ASDAS Low Disease Activity (ASDAS score < 2.1)
9. Study 1: Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI)
10. Study 1: ASAS partial remission (PR) (an absolute score of ≤ 2 units for each of the 4 domains identified in ASAS 40)
11. Study 1: Change from Baseline in Ankylosing Spondylitis Quality of Life (ASQoL)
12. Study 1: Change from Baseline in ASAS Health Index (HI)
13. Study 1: Change from Baseline in linear bath Ankylosing Spondylitis Metrology Index (BASMIlin).
14. Study 1: Change from Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES).
15. Study 2: Change from Baseline in ASDAS
16. Study 2: Change from Baseline in MRI SPARCC score (SI joints)
17. Study 2: BASDAI 50 response
18. Study 2: ASDAS Inactive Disease (ASDAS score < 1.3)
19. Study 2: Change from Baseline in Patient's Assessment of Total Back Pain (Total Back Pain)
20. Study 2: Change from Baseline in Patient's Assessment of Nocturnal Back Pain (Nocturnal Back Pain)
21. Study 2: ASDAS Low Disease Activity (ASDAS score < 2.1)
22. Study 2: ASAS PR (an absolute score of ≤ 2 units for each of the 4 domains identified in ASAS40)
23. Study 2: Change from Baseline in BASFI
24. Study 2: Change from Baseline in ASQoL
25. Study 2: Change from Baseline in ASAS HI
26. Study 2: ASAS20 response
27. Study 2: Change from Baseline in BASMIlin
28. Study 2: Change from Baseline in MASES
29. Study 2: ASAS40 response at Week 52

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Abbvie Deutschland GmbH & Co. KG

Sponsor organisation

Abbvie Deutschland GmbH & Co. KG

Address

Knollstrasse

City

Ludwigshafen Am Rhein

Postcode

67061

Country

Germany

Scientific contact point

Organisation

Abbvie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Public contact point

Organisation

Abbvie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Third parties 4

Locations

9 EU/EEA countries · 39 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 13 files

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

Application history

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