Program to Assess Adverse Events and Change in Disease Activity of Oral Upadacitinib in Adult Participants With Moderate to Severe Systemic Lupus Erythematosus (SELECT-SLE).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Abbvie Deutschland GmbH & Co. KG

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

20 Nov 2023 → ongoing

Decision date (initial)

2023-10-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AbbVie Inc.

External identifiers

EU CT number

2023-503655-10-00

ClinicalTrials.gov

NCT05843643

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Study 1 and Study 2 (Replicate Phase 3 Studies):
The objective is to evaluate the safety and efficacy of upadacitinib compared with placebo for the treatment of signs and symptoms of SLE for 52 weeks in adults with moderately to severely active SLE.
The primary efficacy objective is to demonstrate superiority of upadacitinib compared to placebo with respect to the primary endpoint in adult subjects with moderately to severely active SLE despite background therapy.

Study 3 (Long-term extension):
The primary objective is to evaluate the long-term safety of upadacitinib in adults with moderately to severely active SLE.

Study 4 (Continued Long-term extension)
The primary objective is to evaluate the long-term safety of upadacitinib in adults with moderately to severely active SLE.

Secondary objectives 1

1. Study 1 and Study 2 (Replicate Phase 3 Studies): The secondary efficacy objectives are to demonstrate superiority of upadacitinib compared with placebo with respect to the secondary endpoints for the following categories: SLE disease activity, SLE flares, reduction of glucocorticoid dose, patient-reported outcomes, and damage. Study 3 (Long-term extension): The secondary objectives are to evaluate long-term efficacy of upadacitinib in adults with moderately to severely active SLE, and to evaluate if the efficacy response observed in Study 1 and Study 2 can be maintained on a reduced upadacitinib dose. Study 4 (Continued Long-term extension: The secondary objectives are to describe the long-term efficacy of upadacitinib in adults with moderately to severely active SLE with respect to endpoints for the following categories: SLE disease activity, SLE flares, reduction of oral corticosteroid dose, reduction of other background SLE medications (excluding antimalarials), maintenance of a low disease activity state/remission, and organ damage.

Conditions and MedDRA coding

Systemic Lupus Erythematosus (SLE).

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, Pharmaceuticals And Medical Devices Agency, Medical Products Agency

Plan to share IPD

Yes

IPD plan description

AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information. To learn more about the process, or to submit a request, visit https://www.abbvieclinicaltrials.com/hcp/data-sharing/ For details on when studies are available for sharing, visit https://vivli.org/ourmember/abbvie/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Adult individuals, 18 years (or acceptable age according to local regulations, whichever is older) to 63 years of age, inclusive, at Screening.
2. Clinical diagnosis of SLE at least 24 weeks prior to Screening as defined by the 2019 EULAR/ACR classification criteria for SLE.
3. At Screening, must have at least one of the following: ANA+ (titer ≥1:80); anti-dsDNA+; anti-Smith+
4. hSLEDAI ≥6, of which ≥4 points are clinical (not based on laboratory criteria), independently reviewed by MCDR at Screening. Clinical hSLEDAI score (not based on laboratory criteria) must be re-confirmed as ≥4 at the Baseline visit. Lupus headache or organic brain syndrome do not count towards the hSLEDAI points required for eligibility but should be documented on the hSLEDAI if present.
5. PhGA ≥1 during screening period.
6. On stable background treatment for ≥ 60 days prior to Baseline (with the exception of oral corticosteroid [OCS], which must be at a stable dose for ≥14 days prior to Baseline) with: o antimalarial(s) [hydroxychloroquine ≤400 mg daily, chloroquine ≤500 mg daily, quinacrine ≤100 mg daily]; o and/or prednisone (or prednisone-equivalent) (≤20 mg daily); o and/or no more than 1 of the following: azathioprine (≤150 mg daily), 6-mercaptopurine (≤150 mg daily), mycophenolate mofetil (≤2 g daily), mycophenolate sodium ≤1,440 mg/day, leflunomide (≤20 mg daily), cyclosporine, tacrolimus, voclosporin (≤23.7 mg twice daily), methotrexate (≤25 mg weekly), or mizoribine (≤150 mg daily)

Exclusion criteria 7

1. Laboratory values meeting the following criteria within the screening period prior to Baseline: Serum AST > 2.0 × upper limit of normal ULN; Serum ALT > 2.0 × ULN; Serum albumin < 2.0 g/dL (< 20 g/L); WBC < 1,200/μL; ALC < 300/μL;ANC < 1,000/μL; Platelet count < 50,000/μL; Hemoglobin < 9 g/dL; Estimated GFR by simplified 4-variable MDRD formula < 30 mL/min/1.73 m2 ; Urine protein/creatinine ratio ≥2.5 mg protein/mg creatinine (282.5 mg protein/mmol creatinine).
2. Class III/IV lupus nephritis that was treated with induction therapy within the 6 months prior to Screening.
3. Currently receiving hemodialysis (or other forms of renal replacement therapy)
4. Active neuropsychiatric SLE (excluding lupus headache), as defined by the CNS portion of hSLEDAI or BILAG meeting criteria to score A or B, at Screening, or signs or symptoms of neuropsychiatric SLE (excluding lupus headache) within the 6 months prior to Screening.
5. A known persistent high-risk antiphospholipid antibody profile (defined as lupus anticoagulant, double positivity, or triple positivity) who are not on anticoagulation or on low-dose aspirin, unless a reason to not take low dose aspirin is documented by the investigator (for anti-cardiolipin and anti--β2 glycoprotein-1, the threshold for positivity is > 40 GPL or MPL. Double positivity means 2 of the following, and triple positivity means three, of the following, are positive: lupus anticoagulant, anticardiolipin IgG or IgM, anti-β2 glycoprotein-1 IgG or IgM); For subjects with a known high risk antiphospholipid antibody profile for whom participation in this clinical trial is considered the most suitable treatment option among treatment alternatives and the risks and benefits have been discussed with the subject, the investigator must document a favorable benefit-risk assessment to justify the subject's inclusion in the study.
6. Received IV or IM corticosteroid greater than or equal to a 40 mg prednisone-equivalent bolus within 30 days prior to Baseline; ; or treated with intra-articular, trigger point or tender point, intra-bursa, or intra-tendon sheath corticosteroids in the preceding 30 days prior to Baseline.
7. Prior exposure to a systemic or topical JAK inhibitor (including Tyk2 inhibitors), including but not limited to commercial upadacitinib (Rinvoq®), tofacitinib (Xeljanz®), ruxolitinib (Jakafi® or Opzelura®), delgocitinib (Corectim®), baricitinib (Olumiant®), peficitinib (Smyraf®), abrocitinib (Cibinqo®), filgotinib (Jyseleca®), fedratinib (Inrebic), and deucravacitinib (Sotyktu®).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Study 1 and Study 2: The primary efficacy endpoint is the achievement of BICLA response at Week 52. As part of the additional endpoints, the achievement of BICLA response will also be assessed at all other visits collected; Study 3: There is no primary endpoint in Study 3. Study 4: There is no primary endpoint in Study 4.

Secondary endpoints 10

1. Study 1 and Study 2 The ranked secondary endpoints are: Flare through Week 52. Flare is defined by the SELENA SLEDAI Flare Index (SFI).
2. Achievement of SRI-4 at Week 52.
3. Achievement of LLDAS at Week 52.
4. Time to first flare per SFI through Week 52.
5. Achievement of oral glucocorticoid dose ≤7.5 mg prednisone-equivalent (among subjects taking ≥10 mg prednisone-equivalent at Baseline) from Week 44 to Week 52.
6. Achievement of ≥50% improvement in tender or swollen joints (among subjects with ≥3 swollen joints and ≥6 total affected joints at Baseline) at Week 52.
7. Achievement of ≥50% reduction in CLASI activity score (among subjects with Baseline score ≥10) at Week 52
8. Change from Baseline in FACIT-Fatigue v4 at Week 52.
9. Change from Baseline in Lupus Pain NRS at Week 52.
10. Change from Baseline in SF-36v2® Health Survey Acute PCS at Week 52 As part of the additional endpoints, the endpoints listed above (with the exception of 1, 4, and 5) will also be assessed at all other visits collected. Study 3 There are no ranked secondary endpoints in Study 3. Study 4: There are no ranked secondary endpoints in Study 4.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Abbvie Deutschland GmbH & Co. KG

Sponsor organisation

Abbvie Deutschland GmbH & Co. KG

Address

Knollstrasse

City

Ludwigshafen Am Rhein

Postcode

67061

Country

Germany

Scientific contact point

Organisation

Abbvie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Public contact point

Organisation

Abbvie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Third parties 9

Locations

16 EU/EEA countries · 75 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 207 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

14 submissions — initial application plus substantial / non-substantial modifications