A Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Subjects with Rheumatoid Arthritis who are on a Stable Dose of Methotrexate and Who Have an Inadequate Response to Methotrexate (SELECT-COMPARE)

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

10 May 2016 → ongoing

Decision date (initial)

2023-02-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AbbVie Inc.

External identifiers

EU CT number

2022-501017-31-00

EudraCT number

2015-003333-95

ClinicalTrials.gov

NCT02629159

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Pharmacokinetic, Efficacy, Safety, Pharmacodynamic

Period 1
• To compare the efficacy of upadacitinib QD versus placebo, and versus adalimumab (ADA) for the treatment of signs and symptoms of rheumatoid arthritis (RA) in subjects with moderately to severely active RA who are on a on a stable background of methotrexate (MTX) and who have an inadequate response to MTX (MTX-IR).
• To compare the efficacy of upadacitinib QD versus placebo for the prevention of structural progression in RA subjects with moderately to severely active RA who are on a on a stable background of MTX and who have an inadequate response to MTX (MTX-IR).
• To compare the safety and tolerability of upadacitinib QD versus placebo, and versus ADA in subjects with moderately to severely active RA subjects who are on a stable background of MTX and who have an inadequate response to MTX (MTX-IR).

Period 2
• To evaluate the long-term safety, tolerability, and efficacy of upadacitinib in subjects with RA who have completed Period 1.

Conditions and MedDRA coding

Rheumatoid arthritis

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information. To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/ For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Adult male or female, at least 18 years old.
2. Diagnosis of RA for ≥ 3 months
3. Subjects must have been on oral or parenteral MTX therapy ≥ 3 months and on a stable prescription of 15 to 25 mg/week (or ≥ 10 mg/week in subjects intolerant of MTX at doses ≥ 12.5 mg/week) for ≥ 4 weeks prior to the first dose of study drug. In addition, all subjects should take a dietary supplement of folic acid or folinic acid throughout the study participation.
4. Subjects meeting both: ≥ 6 swollen joints and ≥ 6 tender joints at screening and baseline, and hsCRP ≥ 5 mg/L at screening
5. At least one of the following at Screening: ≥ 3 bone erosions on x-ray OR ≥ 1 bone erosion and a positive rheumatoid factor OR ≥ 1 bone erosion and a positive anti-cyclic citrullinated peptide autoantibodies.
6. Subjects with prior exposure to at most one bDMARD (except ADA) may be enrolled (up to 20% of total study population)
7. Except for MTX, subject must have discontinued all conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs).

Exclusion criteria 3

1. Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
2. Subjects who have had any exposure to adalimumab or subjects who have been treated with other bDMARD therapy for ≥ 3 months who are considered inadequate responders (lack of efficacy) to bDMARD therapy as determined by the Investigator.
3. History of inflammatory joint disease other than RA. History of secondary Sjogren's Syndrome is permitted.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the proportion of subjects achieving ACR20 response at Week 12 or the proportion of subjects achieving clinical remission (CR) based on DAS28 (CRP) at Week 12

Secondary endpoints 14

1. Change from baseline in Disease Activity Score (DAS)28 (C-reactive protein [CRP]) at Week 12
2. Change from baseline in mTSS at Week 26
3. Change from baseline in HAQ-DI at Week 12
4. ACR50 response rate at Week 12 (non-inferiority of upadacitinib versus ADA)
5. Change from baseline in Short Form 36 (SF-36) Physical Component Score (PCS) at Week 12
6. Proportion of subjects achieving low disease activity (LDA) based on DAS28 [CRP] ≤ 3.2 at Week 12
7. Proportion of subjects achieving clinical remission (CR) based on DAS28 (CRP) at Week 12
8. Proportion of subjects achieving LDA based on Clinical Disease Activity Index (CDAI) at Week 12
9. Change from baseline in morning stiffness at Week 12
10. Change from baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) at Week 12
11. ACR50 response rate at Week 12 (superiority of upadacitinib vs. ADA)
12. Change from baseline in Patient's Assessment of Pain at Week 12 (superiority of upadacitinib vs. ADA)
13. Change from baseline in HAQ-DI at Week 12 (superiority of upadacitinib vs. ADA)
14. Other key secondary endpoints (upadacitinib versus placebo): 1) ACR50 response rate at Week 12, 2) ACR70 response rate at Week 12, 3) Proportion of subjects with no radiographic progression (defined as change from baseline mTSS ≤ 0) at Week 26

Investigational products

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

Test 1

Comparator 6

Auxiliary 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

17 EU/EEA countries · 67 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 101 files

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

Application history

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