A Study Investigating the Efficacy and Safety of Upadacitinib (ABT-494) Given With Methotrexate (MTX) in Adults With Rheumatoid Arthritis Who Have Had an Inadequate Response to MTX Alone

Rheumatoid Arthritis Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Investigate the Safety and Efficacy of ABT-494 With Background Methotrexate (MTX) in Subjects With Active Rheumatoid Arthritis (RA) Who Have Had an Inadequate Response to MTX Alone

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02066389
• Other study ID #: M13-537
• Secondary ID: 2013-003984-72
• Status: Completed
• Phase: Phase 2
• Start date: March 26, 2014
• Est. completion date: July 2, 2015

Study information

• Verified date: July 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study was to compare the safety and efficacy of multiple doses of upadacitinib versus placebo in adults with moderately to severely active rheumatoid arthritis (RA) on stable background methotrexate therapy who had not shown an adequate response to methotrexate alone.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: July 2, 2015
• Est. primary completion date: July 2, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

1. Diagnosed with RA based on either the 1987-revised American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European League against Rheumatism (EULAR) criteria for = 3 months.

2. Have active RA as defined by the following minimum disease activity criteria:

• = 6 swollen joints (based on 66 joint counts) at Screening and Baseline Visits.
• = 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
• high-sensitivity C-reactive protein (hsCRP) > upper limit of normal (ULN) OR positive for both rheumatoid factor and anti-cyclic citrullinated peptide (CCP) at Screening.

3. Subjects must have been receiving oral or parenteral methotrexate therapy = 3 months and on a stable prescription of 7.5 to 25 mg/week for at least 4 weeks prior to Baseline Visit. Subjects should also be on a stable dose of folic acid (or equivalent) for at least 4 weeks prior to Baseline Visit. Subjects should continue with their stable doses of methotrexate and folic acid throughout the study.

4. Except for MTX, subjects must have discontinued all oral disease-modifying anti-rheumatic drugs (DMARDs) prior to Baseline Visit as specified below or for at least five times the mean terminal elimination half-life of a drug, whichever is

longer:

• = 4 weeks prior to Baseline Visit for minocycline, penicillamine, sulfasalazine, hydroxychloroquine, chloroquine, azathioprine, gold formulations, cyclophosphamide
• = 8 weeks prior to Baseline Visit for leflunomide if no elimination procedure was followed, or adhere to a washout procedure (i.e., 11 days washout with colestyramine, or 30 days washout with activated charcoal)

5. Subject has a negative tuberculosis (TB) Screening Assessment. If the subject has evidence of a latent TB infection, the subject must initiate and complete a minimum of 2 weeks (or per local guidelines, whichever is longer) of an ongoing TB prophylaxis or have documented completion of a full course of TB prophylaxis, prior to Baseline Visit.

6. Subjects can be taking non-steroidal anti-inflammatory drugs (NSAIDS), acetaminophen, oral corticosteroids (equivalent to prednisone = 10 mg), or inhaled corticosteroids at a stable dose for at least 4 weeks prior to Baseline Visit for stable medical conditions and should be kept at a stable dose throughout the study. NSAIDs, acetaminophen, tramadol, codeine, hydrocodone and propoxyphene taken as needed are allowed but may not be taken 24 hours prior to any study visit. Oral and inhaled corticosteroids taken as needed are allowed but may not be taken 24 hours prior to any study visit.

7. Subjects must have discontinued high potency opiates including (but not limited to):

oxycodone, oxymorphone, fentanyl, levorphanol, buprenorphine, methadone, hydromorphone, and morphine at least 4 weeks prior to Baseline Visit.

Exclusion Criteria:

1. Female who is pregnant or breastfeeding.

2. Prior exposure to Janus activated kinase (JAK) inhibitor (e.g., tofacitinib, baricitinib).

3. Prior exposure to any investigational or approved biologic RA therapy.

4. Receipt of any investigational drug of chemical or biologic nature within a minimum of 30 days or 5 half-lives of the drug (whichever is longer) prior to Week 0 Visit.

5. Current or expected need of other immunosuppressant medications, except methotrexate. Use of oral intake of > 10 mg prednisone/day or equivalent corticosteroid therapy (see inclusion criterion 7).

6. Subject has been treated with intra-articular or parenteral administration of corticosteroids in the preceding 8 weeks prior to the Week 0 Visit.

7. Screening laboratory values meeting the following criteria:

• Serum aspartate transaminase (AST) or alanine transaminase (ALT) > 1.5 × ULN
• Estimated glomerular filtration rate (eGRF) by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 40 mL/min/1.73 m²
• Total white blood cell count (WBC) < 3,000/µL
• Absolute neutrophil count (ANC) < 1,200/µL
• Platelet count < 100,000/µL
• Absolute lymphocytes count < 750/ µL
• Hemoglobin < 9 gm/dL

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Placebo
Tablets for oral administration
• Upadacitinib
Tablets for oral administration

Locations

Country	Name	City	State
Bulgaria	MHAT Kaspela /ID# 127315	Plovdiv
Bulgaria	MHAT Trimontsium /ID# 127311	Plovdiv
Bulgaria	UMHAT Pulmed OOD /ID# 127307	Plovdiv
Bulgaria	Diagnostic Consultative Center /ID# 127313	Sofia
Bulgaria	UMHAT Sv. Ivan Rilski /ID# 127314	Sofia
Bulgaria	UMHAT Sv. Ivan Rilski /ID# 131608	Sofia
Bulgaria	Diagnostic Consultative Center /ID# 127312	Varna
Chile	Corp de Beneficencia Osorno /ID# 127337	Osorno
Chile	Quantum Research LTDA. /ID# 127338	Puerto Varas
Czechia	Revmatologie Bruntal, s.r.o /ID# 126881	Bruntál
Czechia	Artroscan s.r.o. /ID# 126845	Ostrava
Czechia	Revmatologicky ustav Praha /ID# 127317	Prague 2	Praha 2
Czechia	Nuselská poliklinika, Revmatologie /ID# 127318	Prague 4	Praha 4
Hungary	Qualiclinic Kft. /ID# 127340	Budapest III	Pest
Hungary	Veszprem Megyei Csolnoky Feren /ID# 126876	Veszprém
Israel	Barzilai Medical Center /ID# 126875	Ashkelon
Israel	Rambam Health Care Campus /ID# 127341	Haifa
Israel	Sheba Medical Center /ID# 126878	Ramat Gan
Latvia	LTD M&M Centers /ID# 127346	Adazi
Latvia	Arija's Ancane's Family Doctor /ID# 127342	Baldone
Latvia	Clinic ORTO /ID# 127345	Riga
Mexico	Cliditer SA de CV /ID# 127347	Mexico City
Mexico	Clinstile, S.A. de C.V. /ID# 127350	Mexico City
Mexico	Hospital de Jesús Nazareno /ID# 127352	Mexico City
Poland	Gabinet Internistyczno Reum. /ID# 127357	Bialystok	Podlaskie
Poland	Michal Bazela Higher-Med /ID# 127355	Elblag	Warminsko-mazurskie
Poland	Centrum Medyczne Pratia Gdynia /ID# 127360	Gdynia	Pomorskie
Poland	Centrum Medyczne Pratia Krakow /ID# 127358	Krakow	Malopolskie
Poland	REUMED Sp.z o.o. Filia nr 1 /ID# 127353	Lublin	Lubelskie
Poland	Medica Pro Familia S.A Warszawa /ID# 127361	Warsaw	Mazowieckie
Poland	NBR Polska /ID# 127359	Warsaw	Mazowieckie
Puerto Rico	GCM Medical Group /ID# 127363	San Juan
Russian Federation	City Clinical Hospital #7 /ID# 127372	Kazan	Tatarstan, Respublika
Russian Federation	II Dzhan Research Center /ID# 127376	St. Petersburg
Russian Federation	Tver Regional Clinical Hosp. /ID# 127375	Tver	Tverskaya Oblast
Slovakia	MEDMAN s.r.o. /ID# 127381	Martin
Slovakia	Poliklinika Senica /ID# 127396	Senica
South Africa	Panorama Medical Centre /ID# 126846	Cape Town	Western Cape
South Africa	Winelands Medical Research Ctr /ID# 126844	Stellenbosch	Western Cape
Spain	Hospital CIMA Sanitas /ID# 127383	Barcelona
Spain	Hospital Plató /ID# 127384	Barcelona
Spain	Hospital Universitario Basurto /ID# 127391	Bilbao
Spain	Hospital Clin Univ San Carlos /ID# 127382	Madrid
Spain	Hospital Regional de Malaga /ID# 127385	Málaga	Malaga
Spain	Clinica Gaias /ID# 127386	Santiago de Compostela
Spain	Hospital Infanta Luisa /ID# 127389	Sevilla
Spain	Hospital Universitario de Valm /ID# 127387	Sevilla
Turkey	Medeniyet Univ. Goztepe Traini /ID# 132396	Istanbul
Ukraine	Kiev Municipal Clin Hosp 3 /ID# 127419	Kiev
Ukraine	NSC-Strazhesko Ist Cardiology /ID# 127416	Kiev
Ukraine	Sumy State University /ID# 127418	Sumy
United States	Mountain State Clinical Resear /ID# 127089	Clarksburg	West Virginia
United States	Summit Medical Group /ID# 125776	Clifton	New Jersey
United States	Omega Research Consultants, LLC /ID# 125780	DeBary	Florida
United States	Altoona Ctr Clinical Res /ID# 125777	Duncansville	Pennsylvania
United States	C.V. Mehta MD, Med Corporation /ID# 126380	Hemet	California
United States	Accurate Clinical Research /ID# 126535	Houston	Texas
United States	Arthritis and Osteo Assoc /ID# 134994	Las Cruces	New Mexico
United States	North Georgia Rheumatology Grp /ID# 125779	Lawrenceville	Georgia
United States	Lovelace Scientific Resources /ID# 127324	Venice	Florida
United States	The Center for Rheumatology & /ID# 127323	Wheaton	Maryland
United States	PRN Professional Research Network of Kansas, LLC /ID# 126148	Wichita	Kansas
United States	Emkey Arthritis and Osteo Clin /ID# 134716	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Bulgaria,  Chile,  Czechia,  Hungary,  Israel,  Latvia,  Mexico,  Poland,  Puerto Rico,  Russian Federation,  Slovakia,  South Africa,  Spain,  Turkey,  Ukraine, 

References & Publications (1)

Genovese MC, Smolen JS, Weinblatt ME, Burmester GR, Meerwein S, Camp HS, Wang L, Othman AA, Khan N, Pangan AL, Jungerwirth S. Efficacy and Safety of ABT-494, a Selective JAK-1 Inhibitor, in a Phase IIb Study in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate. Arthritis Rheumatol. 2016 Dec;68(12):2857-2866. doi: 10.1002/art.39808. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12	Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria: = 20% improvement in 68-tender joint count; = 20% improvement in 66-swollen joint count; and; = 20% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity; Patient global assessment of disease activity; Patient assessment of pain; Health Assessment Questionnaire - Disability Index (HAQ-DI); High-sensitivity C-reactive protein (hsCRP).	Baseline and Week 12
Secondary	Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12	A participant was a responder if the following 3 criteria for improvement from baseline were met: = 50% improvement in 68-tender joint count; = 50% improvement in 66-swollen joint count; and; = 50% improvement in at least 3 of the 5 following parameters: Physician's global assessment of disease activity; Patient's global assessment of disease activity; Patient's assessment of pain; Health Assessment Questionnaire - Disability Index (HAQ-DI); High sensitivity C-reactive protein (hsCRP).	Baseline and Week 12
Secondary	Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12	A participant was a responder if the following 3 criteria for improvement from baseline were met: = 70% improvement in tender joint count; = 70% improvement in swollen joint count; and; = 70% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity; Patient global assessment of disease activity; Patient assessment of pain; Health Assessment Questionnaire - Disability Index (HAQ-DI); High sensitivity C-reactive protein (hsCRP).	Baseline and Week 12
Secondary	Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12	The disease activity score-28-CRP (DAS28 [CRP]) assesses RA disease activity based on a continuous scale of combined measures of 28 tender joint counts (TJC28), 28 swollen joint counts (SJC28), C-reactive protein (CRP), and the patient global assessment of disease activity (measured on a visual analog scale (VAS) from 0 to 100 mm). DAS28(CRP) scores range from 0 to approximately 10 where higher scores indicate more disease activity.; LDA is defined as a DAS28(CRP) score < 3.2.	Week 12
Secondary	Secondary: Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 12	The disease activity score-28-CRP (DAS28 [CRP]) assesses RA disease activity based on a continuous scale of combined measures of 28 tender joint counts (TJC28), 28 swollen joint counts (SJC28), C-reactive protein (CRP), and the patient global assessment of disease activity (measured on a visual analog scale from 0 to 100 mm). DAS28(CRP) scores range from 0 to 10 where higher scores indicate more disease activity.; CR is defined as a DAS28(CRP) score < 2.6.	Week 12
Secondary	Percentage of Participants Achieving Low Disease Activity (LDA) Based on CDAI at Week 12	The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of TJC28 and SJC28, patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity.; LDA is defined as a CDAI score = 10.	Week 12
Secondary	Percentage of Participants Achieving Clinical Remission Based on CDAI at Week 12	The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of TJC28 and SJC28, patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity.; CR is defined as a CDAI score = 2.8.	Week 12