A safety and efficacy study of ABT-494 in subjects with Giant Cell Arteritis.

• Register: EUCTR
• Last refreshed on: 16 September 2024
• Main ID: EUCTR2017-003978-13-GR
• Date of registration: 18/03/2019
• Prospective Registration: Yes
• Primary sponsor: AbbVie Deutschland GmbH & Co. KG
• Public title: A safety and efficacy study of ABT-494 in subjects with Giant Cell Arteritis.
• Scientific title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Upadacitinib in Subjects with Giant Cell Arteritis: Select-GCA
• Date of first enrolment: 26/07/2019
• Target sample size: 420
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-003978-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Canada, Denmark, France, Germany, Greece, Hungary, Italy, Japan, Netherlands, New Zealand, Portugal, Romania, Russian Federation, Spain, United States

Contacts

• Name: EU Clinical Trials Helpdesk
• Affiliation: AbbVie Ltd

• Name: EU Clinical Trials Helpdesk
• Affiliation: AbbVie Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. Diagnosis of GCA according to the following criteria:
• Adult male or female, at least 50 years of age
• History of ESR = 50 mm/hour or hsCRP/CRP = 1.0 mg/dL
• Presence of at least one of the following:
• Unequivocal cranial symptoms of GCA, OR
• Unequivocal symptoms of 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 magnetic resonance imaging [MRI], computed tomography [CT] or positron emission tomography [PET]) assessed by a qualified radiologist experienced in evaluating large vessel vasculitis, or ultrasound of temporal arteries assessed by a qualified physician experienced in evaluating large vessel vasculitis.
2. Active GCA, either new onset or relapsing, within 8 weeks of study start.
3. Has received treatment with = 40 mg prednisone (or equivalent) at any time prior to study start and be receiving prednisone (or prednisolone) = 20 mg QD at study start.
4. Has GCA that is clinically stable.
5. Females must either be postmenopausal or permanently surgically sterile or, practicing at least 1 specified method of birth control through the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 168
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 252

Exclusion criteria:
Exclusion Criteria:
1. Prior exposure to any JAK inhibitor
2. 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.
3. Subject must not have received a biologic or non-biologic DMARD within at least five times the mean terminal elimination half-life of the drug, or must follow the washout period specified in the protocol
4. Current or past history of infection including herpes zoster or herpes simplex, HIV, active Tuberculosis, active or chronic recurring infection, active hepatitis B or C.
5. Female who is pregnant, breastfeeding, or considering pregnancy during the study




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Giant Cell Arteritis
MedDRA version: 23.1 Level: PT Classification code 10018250 Term: Giant cell arteritis System Organ Class: 10047065 - Vascular disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: Upadacitinib
Product Code: ABT-494
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Upadacitinib
CAS Number: 1310726-60-3
Current Sponsor code: ABT-494
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Upadacitinib
Product Code: ABT-494
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Upadacitinib
CAS Number: 1310726-60-3
Current Sponsor code: ABT-494
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 7.5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Prednisolon 1 mg JENAPHARM
Product Name: Prednisolone
Pharmaceutical Form: Capsule
INN or Proposed INN: PREDNISOLONE
Other descriptive name: PREDNISOLONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Trade Name: Prednisolon 1 mg JENAPHARM
Product Name: Prednisolone
Pharmaceutical Form: Capsule
INN or Proposed INN: PREDNISOLONE
Other descriptive name: PREDNISOLONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Trade Name: Prednisolon 5 mg JENAPHARM
Product Name: Prednisolone
Pharmaceutical Form: Capsule
INN or Proposed INN: PREDNISOLONE
Other descriptive name: PREDNISOLONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Trade Name: Pr

Primary Outcome(s)

Secondary Objective: To evaluate the safety and efficacy of continuing versus withdrawing ABT-494 in maintaining remission in subjects who achieved remission in Period 1.

Main Objective: To evaluate the efficacy of ABT-494 in combination with a corticosteroid taper regimen compared to placebo in combination with a corticosteroid taper regimen, as measured by the proportion of subjects in sustained remission at Week 52, and to assess the safety and tolerability of ABT-494 in subjects with GCA in Period 1.

Timepoint(s) of evaluation of this end point: Week 12-52

Primary end point(s): The proportion of subjects achieving sustained remission at Week 52 as defined as:
• Absence of GCA signs and symptoms from Week 12 through Week 52
• Adherence to the protocol defined corticosteroid taper regimen

Secondary Outcome(s)

Secondary end point(s): The key secondary endpoints include:
1. Proportion of subjects achieving sustained complete remission from Week 12 through Week 52. Sustained complete remission is defined as having achieved all of the following:
- Absence of GCA signs and symptoms from Week 12 through Week 52;
- Normalization of erythrocyte sedimentation rate ([ESR] to < 30 mm/hr without elevation to = 30 mm/hr [attributable to GCA]) from Week 12 through Week 52;
- Normalization of high sensitivity C-reactive protein ([hsCRP] to < 1 mg/dL without elevation (on 2 consecutive visits) to = 1 mg/dL) from Week 12 through Week 52; and
- Adherence to the protocol-defined CS taper regimen.
2. Cumulative CS exposure.
3. Time to first disease flare. Disease flare is defined as an event determined by the investigator to represent recurrence of GCA signs or symptoms or an ESR measurement > 30 mm/hr attributable to GCA, AND requiring an increase in CS dose.
4. Proportion of subjects who experience at least 1 disease flare through Week 52.
5. Proportion of subjects in complete remission at Week 52. Complete remission is defined as having achieved all of the following:
- Absence of GCA signs and symptoms;
- Normalization of ESR to < 30 mm/hr;
- Normalization of hsCRP to < 1 mg/dL; and
- Adherence to the protocol-defined CS taper regimen.
6. Proportion of subjects in complete remission at Week 24.
7. Change from Baseline in the 36-item Short Form Quality of Life Questionnaire (SF-36) Physical Component Score (PCS) at Week 52.
8. Number of disease flares per subject during Period 1.
• Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at Week 52.
• Assessment of Treatment Satisfaction Questionnaire for Medication (TSQM) patient global satisfaction subscale at Week 52.
• Rate of CS-related AEs.

Timepoint(s) of evaluation of this end point: Week 12 to 52

Secondary ID(s)

2017-003978-13-DK

M16-852

Source(s) of Monetary Support

AbbVie Inc.

Ethics review

Status: Approved
Approval date: 26/07/2019
Contact: