A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis (SELECT-GCA)

AbbVie

Status and phase: Active, not recruiting; Phase 3

Conditions: Giant Cell Arteritis (GCA)

Treatments: Other: Placebo; Drug: Upadacitinib; Drug: Corticosteroid (CS)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03725202

2023-505476-29-00 (Other Identifier)

2017-003978-13 (EudraCT Number)

M16-852

Details and patient eligibility

About

This study consists of two periods. The objective of Period 1 is to evaluate the efficacy of upadacitinib in combination with a 26-week corticosteroid (CS) taper regimen compared to placebo in combination with a 52-week CS taper regimen, as measured by the proportion of participants in sustained remission at Week 52, and to assess the safety and tolerability of upadacitinib in participants with giant cell arteritis (GCA). The objective of Period 2 is to evaluate the safety and efficacy of continuing versus withdrawing upadacitinib in maintaining remission in participants who achieved sustained remission in Period 1.

Safety and efficacy data through 06 February 2024 are included in the interim analysis, which was conducted after all participants completed the Week 52 visit or discontinued from the study.

Enrollment: 438 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of giant cell arteritis (GCA) according to the following criteria:

  • History of erythrocyte sedimentation rate (ESR) >= 50 mm/hour or high sensitivity C-reactive protein (hsCRP)/CRP >=1.0 mg/dL
  • Presence of at least one of the following: Unequivocal cranial symptoms of GCA or Unequivocal symptoms of polymyalgia rheumatica (PMR)
  • Presence of at least one of the following: temporal artery biopsy revealing features of GCA or evidence of large vessel vasculitis by angiography or cross-sectional imaging such as ultrasound, magnetic resonance imaging (MRI), computed tomography (CT) or positron emission tomography (PET).

• Active GCA, either new onset or relapsing, within 8 weeks of Baseline.

• Participants must have received treatment with >=40 mg prednisone (or equivalent) at any time prior to Baseline and be receiving prednisone (or equivalent) >= 20 mg once daily (QD) at Baseline.

• Participants must have GCA that, in the opinion of the investigator, is clinically stable to allow the participant to safely initiate the protocol-defined corticosteroid (CS) taper regimen.

• Females must either be postmenopausal or permanently surgically sterile or, practicing at least 1 specified method of birth control through the study.

Exclusion criteria

• Prior exposure to any Janus Kinase (JAK) inhibitor.

• Treatment with an interleukin-6 (IL-6) inhibitor within 4 weeks of study start, or prior treatment with an IL-6 inhibitor and experienced a disease flare during treatment.

• Use of any of the following systemic immunosuppressant treatments within the specified timeframe prior to study start:

  • Anakinra within 1 week of study start.
  • Methotrexate, hydroxychloroquine, cyclosporine, azathioprine, or mycophenolate within 4 weeks of study start.
  • Oral corticosteroid (CS) for conditions other than GCA within 4 week of study start, or intravenous CS within 4 weeks of study start.
  • Greater than or equal to 8 weeks for leflunomide if no elimination procedure was followed, or adhere to an elimination procedure.
  • Cell-depleting agents or alkylating agents including cyclophosphamide within 6 months of study start.

• Current or past history of infection including herpes zoster or herpes simplex, human immunodeficiency virus (HIV), active Tuberculosis, active or chronic recurring infection, active hepatitis B or C.

• Female who is pregnant, breastfeeding, or considering pregnancy during the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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438 participants in 8 patient groups, including a placebo group

Placebo + 52-week CS taper

Placebo Comparator group

Description:

Participants received placebo tablets for upadacitinib administered orally once daily (QD) for 52 weeks and a 52-week corticosteroid (CS) taper regimen during Period 1.

Treatment:

Drug: Corticosteroid (CS)

Other: Placebo

7.5 mg Upadacitinib + 26-week CS taper

Experimental group

Description:

Participants received 7.5 mg upadacitinib tablets administered orally once daily (QD) for 52 weeks and a 26-week corticosteroid (CS) taper regimen during Period 1.

Treatment:

Drug: Corticosteroid (CS)

Drug: Upadacitinib

15 mg Upadacitinib + 26-week CS taper

Experimental group

Description:

Participants received 15 mg upadacitinib tablets administered orally once daily (QD) for 52 weeks and a 26-week corticosteroid (CS) taper regimen during Period 1.

Treatment:

Drug: Corticosteroid (CS)

Drug: Upadacitinib

Placebo + 52-week CS taper -> Placebo

Placebo Comparator group

Description:

Participants who achieved sustained remission for at least 24 weeks prior to the Week 52 visit (at the end of Period 1) OR at remission at the Week 52 visit only who were assigned to placebo tablets for upadacitinib administered orally once daily (QD) in Period 1 continued to receive placebo tablets for upadacitinib administered orally once daily (QD) in Period 2.

Treatment:

Other: Placebo

7.5 mg Upadacitinib + 26-week CS taper -> 7.5 mg Upadacitinib

Experimental group

Description:

Participants received 7.5 mg upadacitinib tablets administered orally once daily (QD) in Period 2.

Treatment:

Drug: Upadacitinib

7.5 mg Upadacitinib + 26-week CS taper -> Placebo

Experimental group

Description:

Participants received placebo tablets for upadacitinib administered orally once daily (QD) in Period 2.

Treatment:

Other: Placebo

15 mg Upadacitinib + 26-week CS taper -> 15 mg Upadacitinib

Experimental group

Description:

Participants received 15 mg upadacitinib tablets administered orally once daily (QD) in Period 2.

Treatment:

Drug: Upadacitinib

15 mg Upadacitinib + 26-week CS taper -> Placebo

Experimental group

Description:

Participants received placebo tablets for upadacitinib administered orally once daily (QD) in Period 2.

Treatment:

Other: Placebo