A Study of the Safety of Oral Elsubrutinib Capsules and Oral Upadacitinib Tablets Given Alone or in Combination (ABBV-599) for Adult Participants With Moderately to Severely Active Systemic Lupus Erythematosus to Assess Change in Disease State
- Conditions
- Systemic Lupus Erythematosus (SLE)
- Interventions
- Registration Number
- NCT04451772
- Lead Sponsor
- AbbVie
- Brief Summary
Systemic Lupus Erythematosus (SLE) is an immune-mediated disease associated with inflammation of multiple organ systems. This study will evaluate how well elsubrutinib and upadacitinib given alone or as the ABBV-599 combination (elsubrutinib/upadacitinib) works within the body, in participants who completed study M19-130. This study will assess the change in disease symptoms.
ABBV-599 is an investigational drug being developed for the treatment of Systemic Lupus Erythematosus (SLE). This study is "double-blinded", which means that neither the trial participants nor the study doctors will know who will be given which study drug. Study doctors put the participants into 1 of 4 groups called treatment arms. Each group receives a different treatment. Adult participants with a diagnosis of SLE will be enrolled. Around 260 participants will be enrolled in the study in approximately 100 sites worldwide.
Participants will receive the following for up to 56 weeks:
Participants will receive oral elsubrutinib capsules and/or oral upadacitinib tablets once daily for up to 56 weeks. Participants who were receiving elsubrutinib and/or upadacitnib in M19-130 will continue to receive the same treatment in this study. Participants who were receiving placebo in M19-130 will be re-randomized to one of the 2 combination treatment arms in this study.
Arm 1: Elsubrutinib Dose A and Upadacitinib Dose A Arm 2: Elsubrutinib Dose A and Upadacitinib Dose B
There may be higher burden for participants in this trial compared to their standard of care. Participants will attend monthly visits during the course of the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 185
- Completed Study M19-130 (i.e., the randomized controlled trial of elsubrutinib, upadacitinib, and ABBV-599 [elsubrutinib/upadacitinib] combination or matching placebo) and will not have developed any laboratory or clinical discontinuation criteria as defined in that study.
- On stable background treatment for SLE throughout the study.
- Active, chronic, or recurrent viral, or bacterial infection.
- Active tuberculosis (TB)
- History of gastrointestinal (GI) perforation, diverticulitis, or a significantly increased risk for GI perforation per investigator assessment.
- Participant require vaccination with live vaccine during study participation.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ABBV-599 High Dose (Elsubrutinib 60 mg/upadacitinib 30 mg) -> ABBV-599 High Dose Elsubrutinib Participants received elsubrutinib 60 mg capsules once a day by mouth and upadacitinib 30 mg film-coated tablets once a day by mouth for 48 weeks in Study M19-130. Participants continued on this regimen in the current study (M20-186) for up to 56 weeks. Elsubrutinib placebo/upadacitinib 30 mg -> Elsubrutinib placebo/upadacitinib 30 mg Placebo for Elsubrutinib Participants received placebo capsules for elsubrutinib once a day by mouth and upadacitinib 30 mg film-coated tablets once a day by mouth for 48 weeks in Study M19-130. Participants continued on this regimen in the current study (M20-186) for up to 56 weeks. ABBV-599 Low Dose (Elsubrutinib 60 mg/upadacitinib 15 mg) -> ABBV-599 Low Dose Upadacitinib Participants received elsubrutinib 60 mg capsules once a day by mouth and upadacitinib 15 mg film-coated tablets once a day by mouth for 48 weeks in Study M19-130. Participants continued on this regimen in the current study (M20-186) for up to 56 weeks. ABBV-599 High Dose (Elsubrutinib 60 mg/upadacitinib 30 mg) -> ABBV-599 High Dose Upadacitinib Participants received elsubrutinib 60 mg capsules once a day by mouth and upadacitinib 30 mg film-coated tablets once a day by mouth for 48 weeks in Study M19-130. Participants continued on this regimen in the current study (M20-186) for up to 56 weeks. Elsubrutinib placebo/upadacitinib 30 mg -> Elsubrutinib placebo/upadacitinib 30 mg Upadacitinib Participants received placebo capsules for elsubrutinib once a day by mouth and upadacitinib 30 mg film-coated tablets once a day by mouth for 48 weeks in Study M19-130. Participants continued on this regimen in the current study (M20-186) for up to 56 weeks. Elsubrutinib placebo/upadacitinib placebo -> ABBV-599 High Dose Upadacitinib Participants received placebo capsules for elsubrutinib once a day by mouth and placebo film-coated tablets for upadacitinib once a day by mouth for 48 weeks in Study M19-130. Participants received elsubrutinib 60 mg capsules once a day by mouth and upadacitinib 30 mg film-coated tablets once a day in the current study (M20-186) for up to 56 weeks. Elsubrutinib 60 mg/upadacitinib placebo -> Elsubrutinib 60 mg/upadacitinib placebo Placebo for Upadacitinib Participants received elsubrutinib 60 mg capsules once a day by mouth and placebo film-coated tablets for upadacitinib once a day by mouth for 48 weeks in Study M19-130. Participants continued on this regimen in the current study (M20-186) for up to 56 weeks. Elsubrutinib placebo/upadacitinib placebo -> ABBV-599 Low Dose Upadacitinib Participants received placebo capsules for elsubrutinib once a day by mouth and placebo film-coated tablets for upadacitinib once a day by mouth for 48 weeks in Study M19-130. Participants received elsubrutinib 60 mg capsules once a day by mouth and upadacitinib 15 mg film-coated tablets once a day by mouth for 48 weeks in the current study (M20-186) for up to 56 weeks. Elsubrutinib placebo/upadacitinib placebo -> ABBV-599 High Dose Elsubrutinib Participants received placebo capsules for elsubrutinib once a day by mouth and placebo film-coated tablets for upadacitinib once a day by mouth for 48 weeks in Study M19-130. Participants received elsubrutinib 60 mg capsules once a day by mouth and upadacitinib 30 mg film-coated tablets once a day in the current study (M20-186) for up to 56 weeks. ABBV-599 Low Dose (Elsubrutinib 60 mg/upadacitinib 15 mg) -> ABBV-599 Low Dose Elsubrutinib Participants received elsubrutinib 60 mg capsules once a day by mouth and upadacitinib 15 mg film-coated tablets once a day by mouth for 48 weeks in Study M19-130. Participants continued on this regimen in the current study (M20-186) for up to 56 weeks. Elsubrutinib 60 mg/upadacitinib placebo -> Elsubrutinib 60 mg/upadacitinib placebo Elsubrutinib Participants received elsubrutinib 60 mg capsules once a day by mouth and placebo film-coated tablets for upadacitinib once a day by mouth for 48 weeks in Study M19-130. Participants continued on this regimen in the current study (M20-186) for up to 56 weeks. Elsubrutinib placebo/upadacitinib placebo -> ABBV-599 Low Dose Elsubrutinib Participants received placebo capsules for elsubrutinib once a day by mouth and placebo film-coated tablets for upadacitinib once a day by mouth for 48 weeks in Study M19-130. Participants received elsubrutinib 60 mg capsules once a day by mouth and upadacitinib 15 mg film-coated tablets once a day by mouth for 48 weeks in the current study (M20-186) for up to 56 weeks.
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-Emergent Adverse Events From the first dose of study drug in Study M20-186 up to 30 days after the last dose of study drug, up to 442 days An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. 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 events (TEAEs) are defined as an adverse event with an onset date that is on or after the first dose of study drug from Study M20-186, and no more than 30 days after the last dose of study drug from Study M20-186. For more details on adverse events please see the Adverse Event section.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI)-4 Baseline of Study M19-130 (Week 0), Weeks 56, 64, 72, 80, 88, 96, 104 SLE Responder Index (SRI)-4 is defined as follows with all criteria compared to Baseline in Study M19-130:
* ≥4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score
* No worsening of the overall condition (\< 0.3 point increase in Physician's Global Assessment \[PhGA\])
* No new British Isles Lupus Assessment Group (BILAG) A or more than 1 new BILAG B disease activity scores (i.e., no organ system changes from baseline B/C/D/E to A and no more than 1 organ system changes from baseline C/D/E to B). A letter score is assigned to each organ system with following indications: A = severe, B = moderate, C = mild, D = inactive with prior history, and E = inactive with no history.Percentage of Participants Achieving British Isles Lupus Assessment Group (BILAG)-Based Combined Lupus Assessment (BICLA) Response Baseline of Study M19-130 (Week 0), Weeks 56, 64, 72, 80, 88, 96, 104 BICLA is a composite responder index. Achievement of BICLA response is defined as improvement in all initial A and B BILAG scores, with no more than one new BILAG B score without worsening of the overall condition (no worsening in Physician's Global Assessment \[PhGA\], \< 0.3 point increase) and no worsening of the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score.
Number of Flares Per Patient-year by Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLE Disease Activity Index (SLEDAI) Flare Index Through Week 104 From Week 56 through Week 104 The SELENA SLEDAI flare index defines mild/moderate or severe SLE flares using the SLEDAI score, definitions of worsening signs and symptoms, treatment changes, and Physician's Global Assessment of Disease Activity.
Change From Baseline in Daily Prednisone Dose Over Time Baseline of M19-130 (Week 0), Weeks 56, 64, 72, 80, 88, 96, 104 Participants'current use of steroid therapy was assessed at each study visit, and the amount of daily prednisone was documented.
Trial Locations
- Locations (87)
Duplicate_AZ Arthritis and Rheumotology Research, PLLC /ID# 227833
🇺🇸Phoenix, Arizona, United States
Duplicate_Arthritis & Rheumatic Disease Specialties /ID# 227828
🇺🇸Aventura, Florida, United States
Duplicate_NYU Langone Health/NYU School of Medicine /ID# 245088
🇺🇸New York, New York, United States
Duplicate_Peking Union Medical College Hospital /ID# 222950
🇨🇳Beijing, Beijing, China
Duplicate_Centro Integral de Reumatologia del Caribe Circaribe SAS /ID# 221879
🇨🇴Barranquilla, Atlantico, Colombia
Duplicate_Centro de Investigacion en Reumatologia y Especialidades Medicas- CIRE /ID# 221884
🇨🇴Bogota, Cundinamarca, Colombia
Healthy Medical Center S.A.S /ID# 221882
🇨🇴Zipaquirá, Cundinamarca, Colombia
Duplicate_Charite Universitaetsmedizin Berlin - Campus Mitte /ID# 222963
🇩🇪Berlin, Germany
Duplicate_Debreceni Egyetem Klinikai Kozpont /ID# 222480
🇭🇺Debrecen, Hajdu-Bihar, Hungary
Duplicate_Azienda Ospedaliero-Universitaria di Ferrara-Arcispedale Sant Anna /ID# 221919
🇮🇹Cona, Ferrara, Italy
Scroll for more (77 remaining)Duplicate_AZ Arthritis and Rheumotology Research, PLLC /ID# 227833🇺🇸Phoenix, Arizona, United States