This study has been transitioned to CTIS with ID 2023-505476-29-00 check the CTIS register for the current data. This study consists of two periods. The objective of Period 1 is to evaluate the efficacy of upadacitinib in combination with a 26-week…
ID
Source
Brief title
Condition
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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
Key secondary endpoints include:
• 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.
• Cumulative CS exposure.
• 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.
• Proportion of subjects who experience at least 1 disease flare through Week
52.
• 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.
• Proportion of subjects in complete remission at Week 24.
• Change from Baseline in the 36-item Short Form Quality of Life Questionnaire
(SF-36) Physical Component Score (PCS) at Week 52.
• 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).
Background summary
Giant cell arteritis (GCA), also known as temporal arteritis, is a systemic
vasculitis of the large vessels with a predilection for the cranial branches of
the aorta. The course of GCA is characterized by a relatively abrupt onset
followed by chronic vascular and systemic inflammation. Corticosteroid (CS)
therapy is the current mainstay of treatment for GCA. Though many symptoms
resolve rapidly with initiation of high dose CS therapy, there are cases
reported of chronic underlying vascular inflammation and progression of
vascular pathology despite control of clinically apparent disease activity.
Thus, there remains the potential for improved treatment options which can
mitigate this subclinical vascular inflammation.
Evidence suggests that inhibition of Janus kinase (JAK)-mediated pathways may
be a promising approach for the treatment of subjects with GCA. More selective
JAK inhibitors may decrease the risk for infection (including viral
reactivation) and/or malignancy that are observed with pan JAK inhibitor or
less selective JAK inhibitors. AbbVie is developing a small molecule inhibitor
of JAK, upadacitinib,that may address the current needs for subjects with GCA.
Study objective
This study has been transitioned to CTIS with ID 2023-505476-29-00 check the CTIS register for the current data.
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 remission in Period 1.
Study design
To evaluate the Safety and Efficacy of Upadacitinib in Subjects with Giant Cell
Arteritis. The study is comprised in 35-day maximum Screening Period: a 52
week randomized, double-blind, parallel-group treatment period (Period 1); a
52-week randomized, blinded extension period (Period 2); and a 30-day follow-up
period.
Intervention
Experimental: Arm A
Upadacitinib dose A administered daily + 26-week CS taper regimen
Experimental: Arm B
Upadacitinib dose B administered daily + 26-week CS taper regimen
Placebo Comparator: Arm C
Placebo administered daily + 52-week CS taper regimen
Study burden and risks
There will be higher burden for subjects participating in this trial compared
to their standard of care. Subject will be visiting the hospital more
frequently. During these visits study procedures will be performed including
blood sampling and questionnaires. Subject will also be tested for TB,
significant heart conditions, pregnancy, HCV/HBV and HIV. Subjects will also
complete a daily diary. Women of Childbearing Potential should practice a
method of birth control, during the study through at least 30 days after the
last dose of study drug.
Subjects will either receive in period 1: upadacitinib + CS taper, or CS taper
+placebo during the study. Subjects will receive upadacitinib or placebo during
period 2 of the study. The most common side effects reported during previous
studies of upadacitinib were headache, upper chest infection, common cold,
diarrhea and cough. An elevation of an enzyme in the blood called creatine
phosphokinase (CPK, a protein released mainly from muscle cells) was observed
in treated patients. The majority of these patients did not have any muscle
symptoms and did not stop study drug because of elevated CPK levels.
The hypothesis that upadacitinib will result in improved ability to maintain
remission with absence of GCA signs and symptoms, indicate that there is an
acceptable rationale to conduct this study. There may or may not be benefit for
study subjects but there may be benefit for future patients with GCA. The
subject*s condition may get better, may worsen, or may stay unchanged.
Wegalaan 9
Hoofddorp 2132 JD
NL
Wegalaan 9
Hoofddorp 2132 JD
NL
Listed location countries
Age
Inclusion criteria
• Adult male or female, at least 50 years of age
• History of ESR >= 50 mm/hour of CRP >= 1.0 mg/dL
• Presence of unequivocal cranial symptoms of GCA or unequivocal symptoms of
polymyalgia
rheumatica
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.
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
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 |
|---|---|
| EU-CTR | CTIS2023-505476-29-00 |
| EudraCT | EUCTR2017-003978-13-NL |
| CCMO | NL68201.042.19 |