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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04451772
Recruitment Status : Enrolling by invitation
First Posted : June 30, 2020
Last Update Posted : October 8, 2020
Sponsor:
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE June 29, 2020
First Posted Date  ICMJE June 30, 2020
Last Update Posted Date October 8, 2020
Actual Study Start Date  ICMJE July 17, 2020
Estimated Primary Completion Date May 22, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 29, 2020)
Number of Participants With Adverse Events [ Time Frame: Through Week 108 ]
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 any event that began or worsened in severity after the first dose of study drug. For more details on adverse events please see the Adverse Event section.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 11, 2020)
  • Systemic Lupus Erythematosus (SLE) Responder Index (SRI)-4 [ Time Frame: Through Week 104 ]
    SRI is a composite responder index based on improvement in disease activity without worsening of the overall condition or the development of significant disease activity in new organ systems.
  • British Isles Lupus Assessment Group (BILAG)-Based Combined Lupus Assessment (BICLA) [ Time Frame: Through Week 104 ]
    BICLA is a composite responder index based on improvement in organ systems without worsening of the overall condition and improvement in disease activity.
  • Change in Steroid Burden [ Time Frame: Baseline of M19-130 (Week 0) Through Week 104 ]
    Steroid Burden is measured as milligrams (mg) of prednisone-equivalent administered.
  • Number of Flares Per Patient-Year (Respectively and Overall) by Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLE Disease Activity Index (SLEDAI) flare index (SFI) [ Time Frame: Through Week 104 ]
    SELENA SLEDAI flare index defines (mild, moderate or severe) SLE flares using the SLEDAI-2K score, disease activity scenarios, treatment changes, and Physician's Global Assessment of Disease Activity.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 29, 2020)
  • Systemic Lupus Erythematosus Responder Index (SRI)-4 [ Time Frame: Through Week 104 ]
    SRI is a composite responder index based on improvement in disease activity without worsening of the overall condition or the development of significant disease activity in new organ systems.
  • British Isles Lupus Assessment Group (BILAG)-Based Combined Lupus Assessment (BICLA) [ Time Frame: Through Week 104 ]
    BICLA is a composite responder index based on improvement in organ systems without worsening of the overall condition and improvement in disease activity.
  • Lupus Low Disease Activity State (LLDAS) [ Time Frame: Through Week 104 ]
    A state of low disease activity based on SLEDAI score (SLEDAI-2K score ≤ 4 excluding SLEDAI-2K activity in major organ systems), absence of systemic lupus erythematosus (SLE) disease activity in major organ systems and new disease activity, Physician's Global Assessment (PhGA) ≤ 1, and concomitant medication usage (steroid dose ≤ 7.5 mg QD and toleration of immunosuppressive drugs at standard maintenance doses).
  • Greater Than or Equal to ≥ 4-Point to 4-Point Decrease in SLE Disease Activity Index (SLEDAI)-2K [ Time Frame: Baseline of M19-130 (Week 0) Through Week 104 ]
    SLEDAI-2K is global SLE disease activity index that focuses on high-impact disease manifestations across the organ systems.
  • Change in Steroid Burden [ Time Frame: Baseline of M19-130 (Week 0) Through Week 104 ]
    Steroid Burden is measured as milligrams (mg) of prednisone-equivalent administered.
  • Number of Flares Per Patient-Year (Respectively and Overall) by Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLEDAI Flare Index (SFI) [ Time Frame: Through Week 104 ]
    SELENA SLEDAI flare index defines (mild, moderate or severe) SLE flares using the SLEDAI-2K score, disease activity scenarios, treatment changes, and Physician's Global Assessment of Disease Activity.
  • Achievement of 50% Reduction of Tender or Swollen Lupus Joints (of Those Starting With Total ≥ 6 Affected Joints) [ Time Frame: Baseline of M19-130 (Week 0) Through Week 104 ]
    Achievement of 50% reduction in number of tender or swollen lupus joints of those starting with ≥ 6 affected joints as assessed by physical examination.
  • Achievement of 50% Reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score, for those starting wtih CLASI ≥ 10 at M19-130 baseline [ Time Frame: Baseline of M19-130 (Week 0) Through Week 104 ]
    CLASI is an index used to assess cutaneous manifestations of SLE summarizing the activity of the disease.
  • Change in SLEDAI-2K [ Time Frame: Baseline of M19-130 (Week 0) Through Week 104 ]
    SLEDAI-2K is global SLE disease activity index that focuses on high-impact disease manifestations across the organ systems.
  • Change in BILAG [ Time Frame: Baseline of M19-130 (Week 0) Through Week 104 ]
    BILAG is a global disease activity index based on the physician's intention to treat, focusing on changes in disease manifestations.
  • Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) [ Time Frame: Baseline of M19-130 (Week 0) Through Week Week 96 ]
    FACIT-F is a patient-reported questionnaire developed to assess fatigue. The responses to the items on the FACIT-F questionnaire are each measured on a 4-point Likert scale.
  • Change in 36-Item Short Form Health Survey (SF-36) [ Time Frame: Baseline of M19-130 (Week 0) Through Week 96 ]
    SF-36 is a general Health Related Quality of Life (HRQoL) instrument which comprises 36 total questions targeting participant's functional health and well-being.
  • Change in Lupus Quality of Life questionnaire (LupusQoL) [ Time Frame: Baseline of M19-130 (Week 0) Through Week 96 ]
    The Lupus Quality of Life (LupusQoL) is a disease-specific Health Related Quality of Life (HRQoL) patient reported outcome (PRO) instrument.
  • Change in Pain Numerical Rating Scale (NRS) [ Time Frame: Baseline of M19-130 (Week 0) Through Week 96 ]
    The pain NRS scale is a single item questionnaire in which participants are asked to rate the overall pain level. The pain NRS scores range from 0 to 10, with higher scores indicating a higher level of pain.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE A Phase 2, Long-Term Extension (LTE) Study With Elsubrutinib and Upadacitinib Given Alone or in Combination (ABBV-599) in Subjects With Moderately to Severely Active Systemic Lupus Erythematosus Who Have Completed the M19-130 Phase 2 Randomized Controlled Trial (RCT)
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 300 participants will be enrolled in the study in approximately 146 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 4 treatment arms in this study.

Arm 1: Elsubrutinib Dose A and Upadacitinib Dose A Arm 2: Elsubrutinib Dose A and Upadacitinib Dose B Arm 3: Elsubrutinib Dose A and Upadacitinib Placebo Arm 4: Elsubrutinib Placebo and Upadacitinib Dose A

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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Systemic Lupus Erythematosus (SLE)
Intervention  ICMJE
  • Drug: Elsubrutinib
    Oral; Capsule
    Other Name: ABBV-105
  • Drug: Placebo for Elsubrutinib
    Oral; Capsule
  • Drug: Upadacitinib
    Oral; Tablet
    Other Names:
    • ABT-494
    • RINVOQ
  • Drug: Placebo for Upadacitinib
    Oral; Tablet
Study Arms  ICMJE
  • Experimental: Part 1: Elsubrutinib Dose A and Upadacitinib Dose A
    Participants will receive Elsubrutinib Dose A and Upadacitinib Dose A once daily (QD).
    Interventions:
    • Drug: Elsubrutinib
    • Drug: Upadacitinib
  • Experimental: Part 2: Elsubrutinib Dose A and Upadacitinib Dose B
    Participants will receive Elsubrutinib Dose A and Upadacitinib Dose B QD.
    Interventions:
    • Drug: Elsubrutinib
    • Drug: Upadacitinib
  • Experimental: Part 3: Elsubrutinib Dose A and Upadacitinib Placebo
    Participants will receive Elsubrutinib Dose A and Upadacitinib placebo QD.
    Interventions:
    • Drug: Elsubrutinib
    • Drug: Placebo for Upadacitinib
  • Experimental: Part 4: Elsubrutinib Placebo and Upadacitinib Dose A
    Participants will receive Elsubrutinib placebo and Upadacitinib Dose A QD.
    Interventions:
    • Drug: Placebo for Elsubrutinib
    • Drug: Upadacitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Enrolling by invitation
Estimated Enrollment  ICMJE
 (submitted: September 15, 2020)
300
Original Estimated Enrollment  ICMJE
 (submitted: June 29, 2020)
260
Estimated Study Completion Date  ICMJE May 22, 2023
Estimated Primary Completion Date May 22, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Completed Study M19-130 (i.e., the preceding study of elsubrutinib, upadacitinib, and ABBV-599 [elsubrutinib/upadacitinib] combination) 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.

Exclusion Criteria:

  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Bulgaria,   China,   Hungary,   Netherlands,   Poland,   Puerto Rico,   Spain,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04451772
Other Study ID Numbers  ICMJE M20-186
2020-001690-72 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: AbbVie Inc. AbbVie
PRS Account AbbVie
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP