A Study in Rheumatoid Arthritis Patients Who Have Completed a Preceding Study With ABBV-105 Given Alone or in Combination With Upadacitinib
- Conditions
- Rheumatoid Arthritis (RA)
- Interventions
- Registration Number
- NCT03823378
- Lead Sponsor
- AbbVie
- Brief Summary
This was a long-term extension (LTE) study to assess the safety, tolerability, and efficacy of ABBV-105 (elsubrutinib \[ELS\]) and ABBV-599 (ELS 60 mg and upadacitinib \[UPA\] 15 mg) in participants with rheumatoid arthritis (RA) who completed Study M16-063 (NCT03682705).
- Detailed Description
This was a Phase 2, double-blind, multicenter, long-term extension (LTE) study to assess the safety, tolerability, and efficacy of 3 doses of ABBV-105 (elsubrutinib \[ELS\] 5 mg, 20 mg, and 60 mg) and ABBV-599 (ELS 60 mg and upadacitinib \[UPA\] 15 mg) in adults with active rheumatoid arthritis with inadequate response or intolerance to biologic disease-modifying antirheumatic drugs (bDMARDs). Participants who successfully completed treatment in the feeder Study M16-063, a Phase 2 dose exploratory study, were eligible to participate in this study. Those who met eligibility criteria and entered this study receiving ELS, ABBV-599, or UPA from Study M16-063 continued on their previously assigned treatment through termination of this study. Participants originally randomized to placebo in Study M16-063 rolled over to ABBV-599 in a blinded fashion in this study.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 97
- Participant has completed Study M16-063
- Participant has not developed any laboratory or clinical discontinuation criteria as defined in the Study M16-063 protocol
- Participant is willing and/or able to comply with procedures required in the current study protocol
- Participant is currently enrolled or planning to enroll in another interventional clinical study while participating in this study (except the preceding study M16-063)
- Participant requires vaccination with any live vaccine during study participation, including at least 30 days after the last dose of study drug
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ABBV-105 5 mg/UPA placebo Placebo for upadacitinib 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks ABBV-105 60 mg/UPA placebo Placebo for upadacitinib 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks ABBV-599 in M16-063/ABBV-599 in M16-763 Elsubrutinib 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks ABBV-105 20 mg/UPA placebo Elsubrutinib 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks UPA 15 mg/ABBV-105 placebo Placebo for elsubrutinib 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks ABBV-105 20 mg/UPA placebo Placebo for upadacitinib 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks Placebo in M16-063/ABBV-599 in M16-763 Elsubrutinib Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 ABBV-105 60 mg/UPA placebo Elsubrutinib 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks ABBV-105 5 mg/UPA placebo Elsubrutinib 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks ABBV-599 in M16-063/ABBV-599 in M16-763 Upadacitinib 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks UPA 15 mg/ABBV-105 placebo Upadacitinib 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks Placebo in M16-063/ABBV-599 in M16-763 Upadacitinib Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs) On or after the first dose of study drug in Study M16-763, and up to 30 days after the last dose of study drug in Study M16-763, up to 52 weeks An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug as either having a reasonable possibility or no reasonable possibility. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein (DAS28-CRP) Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Low Disease Activity (LDA) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than or equal to 3.2.
Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein (DAS28-CRP) Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Clinical Remission (CR) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than 2.6.
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 Participants who met the following 3 conditions for improvement from baseline of Study M16-063 were classified as meeting the American College of Rheumatology 70% response (ACR70) criteria:
1. ≥ 70% improvement in 68-tender joint count from Baseline of Study M16-063
2. ≥ 70% improvement in 66-swollen joint count from Baseline of Study M16-063 and
3. ≥ 70% improvement in at least 3 of the 5 following parameters from Baseline of Study M16-063:
* Patient's Assessment of Pain (Visual Analog Scale \[VAS\])
* Patient's Global Assessment of Disease Activity (PtGA)
* Physician's Global Assessment of Disease Activity (PhGA)
* Health Assessment Questionnaire Disability Index (HAQ-DI)
* High-sensitivity C-reactive protein (hsCRP)Change in Swollen Joint Count 66 (SJC66) From Baseline of Study M16-063 Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 Sixty-six joints were assessed for swelling by physical examination. Swelling of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with swelling) to 66 (worst possible score/66 joints with swelling). Negative values indicate improvement from baseline.
Change in Tender Joint Count 68 (TJC68) From Baseline of Study M16-063 Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 Sixty-eight joints were assessed for tenderness by physical examination. Pain or tenderness of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with tenderness) to 68 (worst possible score/68 joints with tenderness). Negative values indicate improvement from baseline.
Change in Participant's Assessment of Pain (Visual Analog Scale [VAS]) From Baseline of Study M16-063 Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 Participants rated their pain on a visual analogue scale (VAS) of 0 to 100 (mm), with 0 representing no pain and 100 representing the worst possible pain. Negative values indicate improvement from baseline.
Change in Patient's Global Assessment of Disease Activity (PtGA) From Baseline of Study M16-063 Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 Participants rated their disease activity for the past 24 hours using a Patient's Global Assessment of Disease Activity Global visual analogue scale (VAS). The range is 0 to 100 mm, with 0 representing no disease activity and 100 representing severe disease activity. Negative values indicate improvement from baseline.
Change in Disease Activity Score 28 C-reactive Protein (DAS28-CRP) From Baseline of Study M16-063 at Each Study Visit in Study M16-763 Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline indicates improvement in disease activity.
Change in Clinical Disease Activity Index (CDAI) From Baseline of Study M16-063 Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), 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. A negative change from Baseline indicates improvement in disease activity.
Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), 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. Low Disease Activity (LDA) based on CDAI is defined as achieving a total CDAI score of less than or equal to 10.
Percentage of Participants Achieving Clinical Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), 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. Complete Remission (CR) based on CDAI is defined as achieving a total CDAI score of less than or equal to 2.8.
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 Participants who met the following 3 conditions for improvement from baseline of Study M16-063 were classified as meeting the American College of Rheumatology 20% response (ACR20) criteria:
1. ≥ 20% improvement in 68-tender joint count from Baseline of Study M16-063
2. ≥ 20% improvement in 66-swollen joint count from Baseline of Study M16-063 and
3. ≥ 20% improvement in at least 3 of the 5 following parameters from Baseline of Study M16-063:
* Patient's Assessment of Pain (Visual Analog Scale \[VAS\])
* Patient's Global Assessment of Disease Activity (PtGA)
* Physician's Global Assessment of Disease Activity (PhGA)
* Health Assessment Questionnaire Disability Index (HAQ-DI)
* High-sensitivity C-reactive protein (hsCRP)Change in Health Assessment Questionnaire Disability Index (HAQ-DI) From Baseline of Study M16-063 Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. A negative change from baseline in the overall score indicates improvement.
Change in High-Sensitivity C-Reactive Protein (Hs-CRP) From Baseline of Study M16-063 Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 C-reactive protein is a blood test marker for inflammation in the body, and levels rise in response to inflammation. A negative change from baseline indicates improvement.
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 Participants who met the following 3 conditions for improvement from baseline of Study M16-063 were classified as meeting the American College of Rheumatology 50% response (ACR50) criteria:
1. ≥ 50% improvement in 68-tender joint count from Baseline of Study M16-063
2. ≥ 50% improvement in 66-swollen joint count from Baseline of Study M16-063 and
3. ≥ 50% improvement in at least 3 of the 5 following parameters from Baseline of Study M16-063:
* Patient's Assessment of Pain (Visual Analog Scale \[VAS\])
* Patient's Global Assessment of Disease Activity (PtGA)
* Physician's Global Assessment of Disease Activity (PhGA)
* Health Assessment Questionnaire Disability Index (HAQ-DI)
* High-sensitivity C-reactive protein (hsCRP)Change in Physician's Global Assessment of Disease Activity (PhGA) From Baseline of Study M16-063 Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 The physician assessed a participant's disease activity at the time of the visit using a Physician's Global Assessment of Disease visual analogue scale (VAS). The range is 0 to 100 mm, with 0 representing no disease activity and 100 representing severe disease activity. Negative values indicate improvement from baseline.
Change in Morning Stiffness Severity From Baseline of Study M16-063 Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 Morning stiffness severity was assessed by a numeric rating-scale (NRS). Participants rated the severity of morning stiffness during the past week from 0 to 10 with 0 representing "not severe" and 10 "very severe". Negative values indicate improvement from baseline.
Trial Locations
- Locations (30)
ClinicMed Daniluk, Nowak Sp.j. /ID# 212578
🇵🇱Białystok, Podlaskie, Poland
CMED Rehabilitacios es Diagnosztikai Kozpont /ID# 208188
🇭🇺Szekesfehervar, Hungary
NBR Polska /ID# 209904
🇵🇱Warsaw, Mazowieckie, Poland
Malopolskie Centrum Kliniczne /ID# 209902
🇵🇱Cracow, Malopolskie, Poland
Dr. Latha Naik /ID# 213440
🇨🇦Saskatoon, Saskatchewan, Canada
Szabolcs-Szatmar-Bereg Megyei Korhazak & Egyetemi Oktatokorhaz /ID# 208184
🇭🇺Nyíregyháza, Szabolcs-Szatmar-Bereg, Hungary
Vital Medical Center Orvosi-es Fogaszati Kozpont /ID# 208185
🇭🇺Veszprem, Hungary
Revita Reumatologiai Rendelo /ID# 208187
🇭🇺Budapest, Hungary
CIADS Research Co Ltd /ID# 206853
🇨🇦Winnipeg, Manitoba, Canada
Manitoba Clinic /ID# 206852
🇨🇦Winnipeg, Manitoba, Canada
UZ Leuven /ID# 207722
🇧🇪Leuven, Belgium
CRU Hungary Egeszsegugyi és Szolgaltato Kft. /ID# 208186
🇭🇺Miskolc, Borsod-Abauj-Zemplen, Hungary
Cliniques Universitaires Saint Luc /ID# 207719
🇧🇪Woluwe-Saint-Lambert, Bruxelles-Capitale, Belgium
Rheumatology Research Assoc /ID# 207769
🇨🇦Edmonton, Alberta, Canada
Mount Sinai Hosp.-Toronto /ID# 206851
🇨🇦Toronto, Ontario, Canada
Revmatologicky ustav Praha /ID# 209943
🇨🇿Prague 2, Praha 2, Czechia
Revmatolog s.r.o. /ID# 209941
🇨🇿Jihlava 1, Jihlava, Czechia
McBk Sc /Id# 212577
🇵🇱Grodzisk Mazowiecki, Mazowieckie, Poland
Hospital Clinico Universitario San Carlos /ID# 207738
🇪🇸Madrid, Spain
Revmatologie MUDr. Klara Sirova /ID# 209944
🇨🇿Ostrava, Czechia
Hospital Universitario Basurto /ID# 207737
🇪🇸Bilbao, Spain
CCR Czech a.s /ID# 209942
🇨🇿Pardubice, Czechia
Reumatika - Centrum Reumatologii NZOZ /ID# 209903
🇵🇱Warsaw, Poland
Hospital Universitario A Coruña - CHUAC /ID# 207732
🇪🇸A Coruña, A Coruna, Spain
Hospital Regional de Malaga /ID# 207735
🇪🇸Málaga, Malaga, Spain
Hospital Clinic /ID# 207740
🇪🇸Barcelona, Spain
University of Oxford /ID# 210571
🇬🇧Oxford, United Kingdom
Hospital Universitario Virgen de las Nieves /ID# 209975
🇪🇸Granada, Spain
Hospital Universitario y Politecnico La Fe /ID# 207739
🇪🇸Valencia, Spain
Hospital Unversitario Marques de Valdecilla /ID# 207729
🇪🇸Santander, Cantabria, Spain