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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04451772
Recruitment Status : Recruiting
First Posted : June 30, 2020
Last Update Posted : July 23, 2020
Sponsor:
Information provided by (Responsible Party):
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 146 sites worldwide.

Participants will receive the following for up to 56 weeks:

Participants will receive oral elsubrutinib capsules 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.


Condition or disease Intervention/treatment Phase
Systemic Lupus Erythematosus (SLE) Drug: Elsubrutinib Drug: Placebo for Elsubrutinib Drug: Upadacitinib Drug: Placebo for Upadacitinib Phase 2

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Study Type : Interventional
Estimated Enrollment : 260 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : July 17, 2020
Estimated Primary Completion Date : May 17, 2023
Estimated Study Completion Date : May 17, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lupus

Arm Intervention/treatment
Experimental: Part 1: Elsubrutinib Dose A and Upadacitinib Dose A
Participants will receive Elsubrutinib Dose A and Upadacitinib Dose A once daily (QD).
Drug: Elsubrutinib
Oral; Capsule
Other Name: ABBV-105

Drug: Upadacitinib
Oral; Tablet
Other Name: ABT-494

Experimental: Part 2: Elsubrutinib Dose A and Upadacitinib Dose B
Participants will receive Elsubrutinib Dose A and Upadacitinib Dose B QD.
Drug: Elsubrutinib
Oral; Capsule
Other Name: ABBV-105

Drug: Upadacitinib
Oral; Tablet
Other Name: ABT-494

Experimental: Part 3: Elsubrutinib Dose A and Upadacitinib Placebo
Participants will receive Elsubrutinib Dose A and Upadacitinib placebo QD.
Drug: Elsubrutinib
Oral; Capsule
Other Name: ABBV-105

Drug: Placebo for Upadacitinib
Oral; Tablet

Experimental: Part 4: Elsubrutinib Placebo and Upadacitinib Dose A
Participants will receive Elsubrutinib placebo and Upadacitinib Dose A QD.
Drug: Placebo for Elsubrutinib
Oral; Capsule

Drug: Upadacitinib
Oral; Tablet
Other Name: ABT-494




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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).

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) [ Time Frame: Baseline of M19-130 (Week 0) Through 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 5-point Likert scale. Items are scored on a 0 - 4 response scale, ranging from "Not at all" to "Very much." All items are summed, with reverse scoring applied where appropriate (Items An5 "I have energy" and An7 "I am able to do my usual activities"). The sum creates a single fatigue score ranging from 0 - 52, with higher scores representing less fatigue or better functioning.

  12. 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.

  13. 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.

  14. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Completed Study M19-130 (i.e., the preceding study of elsubrutinib, upadacitinib, and ABBV599 [elsubrutinib/upadacitinib] combination).
  • On stable background treatment for SLE throughout the study.

Exclusion Criteria:

  • Active, chronic, or recurrent viral infection.
  • Require vaccination with any live vaccine during study participation.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04451772


Contacts
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Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com

Locations
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Sponsors and Collaborators
AbbVie
Investigators
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Study Director: AbbVie Inc. AbbVie
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT04451772    
Other Study ID Numbers: M20-186
2020-001690-72 ( EudraCT Number )
First Posted: June 30, 2020    Key Record Dates
Last Update Posted: July 23, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
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

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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
Keywords provided by AbbVie:
Systemic Lupus Erythematosus
ABBV-599
ABBV-105
ABT-494
Elsubrutinib
Upadacitinib
Additional relevant MeSH terms:
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Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Upadacitinib
Janus Kinase Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents