The main objective of this study is to evaluate the safety and efficacy of ABBV-105, upadacitinib, and ABBV-599 versus placebo for the treatment of signs and symptoms of SLE in participants with moderately to severely active SLE and to define doses…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
SLE Responder Index (SRI)-4 and steroid dose <= 10 mg prednisone equivalent QD
at Week 24.
SLE Responder Index (SRI)-4 is defined as >= 4-point reduction in Systemic Lupus
Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score without worsening
of the overall condition (no worsening in Physician's Global Assessment (PhGA),
< 0.3 point increase) or the development of significant disease activity in new
organ systems (no new British Isles Lupus Assessment Group ([BILAG]) A or > 1
new BILAG B).
Secondary outcome
1. SRI-4 (without <= 10 mg prednisone equivalent once a day [QD] requirement)
2. SRI-5, -6, -7, -8 (and steroid dose <= 10 mg prednisone equivalent QD at
Weeks 24 and 48; without <= 10 mg prednisone equivalent QD requirement at all
other visits)
3. BILAG Based Combined Lupus Assessment (BICLA)
4. Lupus Low Disease Activity State (LLDAS)
5. Change in SLEDAI-2K
6. Steroid burden, assessed as change from baseline
7. Number of flares by Safety of Estrogens in Lupus Erythematosus National
Assessment SELENA SLEDAI flare index, assessed by number and types of flare per
patient compared across treatment arms
8. Time to first flare by SELENA SLEDAI flare index after first study drug
administration up to Week 24 and Week 48.
9. Achievement of 50% reduction of tender or swollen lupus joints (of those
starting with >=6 joints) (defined as >=50% decrease in either tender or swollen
joints (among those starting with >=6 affected joints)
10. Achievement of 50% reduction in Cutaneous Lupus Erythematosus Disease Area
and Severity Index (CLASI) activity score (of those starting with CLASI >=10)
11. Change in SLEDAI-2K from Baseline
12. Change in BILAG from Baseline
13. Change in PhGA from Baseline
14. Change from Baseline Functional Assessment of Chronic Illness Therapy -
fatigue (FACIT-F) at Weeks 2, 12, 24, and 48
15. Change from Baseline in SF-36 at Weeks 2, 12, 24 and 48
16. Change from Baseline Lupus Quality of Life questionnaire (LupusQoL) at
Weeks 2, 12, 24 and 48
17. Change from Baseline Pain Numerical Rating Scale (NRS) at Weeks 2, 12, 24
and 48
Background summary
Systemic Lupus Erythematosus (SLE) is a long-term, autoimmune disease that
causes inflammation (swelling) and pain in connective tissues and affects
several organs. In addition to affecting skin and joints, SLE can also affect
the kidneys, lungs, heart, and brain. Some symptoms of SLE are extreme
tiredness, discomfort, fever, loss of appetite, joint pain, muscle pain, and
weakness. Skin problems like a flat, red rash across cheeks and bridge of
nose, called *butterfly rash* can occur. About one-third of people with SLE
develop kidney disease. People with SLE have episodes in which the condition
gets worse and other times, when it gets better. The purpose of the study is
to see if ABBV-105 and upadacitinib, given alone or in combination are safe and
effective to treat signs and symptoms of SLE.
Study objective
The main objective of this study is to evaluate the safety and efficacy of
ABBV-105, upadacitinib, and ABBV-599 versus placebo for the treatment of signs
and symptoms of SLE in participants with moderately to severely active SLE and
to define doses for further development.
Study design
Randomised, double blind, parallel group, placebo controlled.
Intervention
Oral ABBV-105 and/or upadacitinib and/or matching placebo administered during
the 48-week treatment period.
Study burden and risks
There will be a higher treatment burden for participants in this trial compared
to their standard of care. Participants will attend regular visits during the
study at a hospital or clinic. The effect of the treatment will be checked by
medical assessments, blood tests, and checking for side effects and completing
questionnaires.
Knollstrasse 50
Ludwigshafen 67061
DE
Knollstrasse 50
Ludwigshafen 67061
DE
Listed location countries
Age
Inclusion criteria
• Adult male or female, 18 -65 years of age, inclusive, at Screening
• SLE by ACR 2012 or SLICC Diagnostic Criteria
• At Screening, must have at least one of the following:
* ANA+ (titer >= 1:80)
* anti-dsDNA+
* anti-Smith+
• SLEDAI-2K >= 6 as reported and independently adjudicated (excluding lupus
headache and/or organic brain syndrome) (clinical score >= 4) at Screening. If 4
points of the required entry points are for arthritis there must also be a
minimum of 3 tender and 3 swollen joints
* If subject has rash and PI considers it to be attributable to SLE, subject
must consent to skin photograph collection for adjudication.
* Score must be re-confirmed at the Baseline Visit
• Must be on background treatment, stable for 30 days prior to baseline, and
throughout the study with prednisone (or prednisone equivalent) (<=20mg),
antimalarials, azathioprine (<= 150mg), mycophenolate (<= 2g), leflunomide (<=
20mg) and/or methotrexate (MTX) (<= 20mg), cyclosporine, tacrolimus;
* The combination of background treatment with antimalarial(s) and/or
prednisone (or equivalent) is permitted.
* and a single, but not multiple, additional immunosuppressant from the list
above, is permitted
Exclusion criteria
• Women of childbearing potential must not have a positive serum pregnancy test
at the screening visit and must have a negative urine pregnancy test at
baseline prior to the first dose of study drug. Note: Subjects with borderline
serum pregnancy tests at Screening must have a serum pregnancy test >= 3 days
later to document continued lack of positive result.
• Must not be using IV or IM corticosteroids greater than or equal to a 40 mg
prednisone-equivalent bolus within 30 days weeks of planned randomization
• Must not have active lupus nephritis (progressive Class IV or >1g/d
proteinuria) or have undergone induction therapy within the last 6 months.
• Must not have active neuropsychiatric SLE as defined by the CNS portion of
SLEDAI-2K (excluding lupus headache).
Subjects must be naïve or have discontinued the following prior to the first
dose of study drug per the applicable washout period below or should be at
least 5 times the mean terminal elimination half-life of a drug:
* >=6 months for Plasmapheresis
* >=3 months for Benlysta
* >=1 year for rituximab OR >= 6 months if B cells have returned to >= 50 B cells
per microliter
* >=3 months for cyclophosphamide
* >=4 weeks for abatacept, any anti-TNF therapy, and all other biologics
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-00638-20-NL |
| ClinicalTrials.gov | NCT03978520 |
| CCMO | NL71250.056.19 |