This study has been transitioned to CTIS with ID 2023-505699-31-00 check the CTIS register for the current data. To evaluate the Long-Term Safety and Efficacy of upadacitinib.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of the study is to evaluate the long-term safety and
tolerability of upadacitinib through the assessment of the incidence of
treatment-emergent adverse events, changes in vital signs, physical examination
results, and clinical laboratory data.
Secondary outcome
The clinical remission or response will be evaluated using the Mayo Scoring
System for Assessment of Ulcerative Colitis Activity (Full Mayo score), Adapted
Mayo score (Full Mayo score excluding Physician's Global Assessment), or
Partial Mayo score (Full Mayo score excluding endoscopic subscore).
Background summary
Ulcerative colitis (UC) is a chronic, relapsing inflammatory disease of the
large intestine characterized by inflammation and ulceration of mainly the
mucosal and occasionally submucosal intestinal layers. The hallmark clinical
symptoms include bloody diarrhea associated with rectal urgency and tenesmus.
The most severe intestinal manifestations of UC are toxic megacolon and
perforation. Patients with UC are at an increased risk for colon cancer, and
the risk increases with the duration of disease as well as extent of colon
affected by the disease. The aim of medical treatment in UC is to control
inflammation and reduce symptoms. Available pharmaceutical therapies are
limited, do not always completely abate the inflammatory process, and may have
significant adverse effects. Therapies for mild to moderate active UC include
5-aminosalicylic acid derivatives and immunosuppressants. Corticosteroids are
used in patients with more severe symptoms but are not useful for longer term
therapy. The frequency and severity of corticosteroid toxicities are
significant, including infections, emotional and psychiatric disturbances, skin
injury, and metabolic bone disease. Patients with moderate to severe symptoms
may derive some benefits from immunomodulatory agents, however, the use of
these agents is limited as induction treatment due to a slow onset of action (3
to 6 months) and as maintenance therapy due to adverse events (AEs), including
bone marrow suppression, infections, hepatotoxicity, pancreatitis, and
malignancies. Biological agents targeting specific immunological pathways have
been evaluated for their therapeutic effect in treating patients with UC as
well, such as anti-tumor necrosis factor (TNF) agents. Anti-TNF therapies are
an effective treatment for patients who are steroid refractory or steroid
dependent, who had inadequate response to a thiopurine, or who are intolerant
to these medications. Potential risks with anti-TNF therapies include infusion
or injection site reactions, serious infections, lymphoma, heart failure,
lupus-like syndromes, and demyelinating conditions. Despite the beneficial
results achieved with the available biologic agents, only 17% to 45% of
patients who receive them are able to achieve clinical remission. Thus, there
remains a clear medical need for additional therapeutic options in UC for
patients with inadequate response to or intolerance to conventional therapies
and biologic therapies. The Janus kinases or JAKs are a family of intracellular
tyrosinekinases that function as dimers in the signaling process of many
cytokine receptors. The JAKs play a critical role in both innate and adaptive
immunity, making them attractive targets for the treatment of inflammatory
diseases. Targeting the Janus activated kinase (JAK) signaling pathway for
autoimmune diseases is supported by the involvement of various pro-inflammatory
cytokines that signal via JAK pathways in the pathogenesis of these
immune-related disorders. Upadacitinib is a novel selective JAK1 inhibitor.
JAK1 inhibition blocks the signaling of many important pro-inflammatory
cytokines.
Study objective
This study has been transitioned to CTIS with ID 2023-505699-31-00 check the CTIS register for the current data.
To evaluate the Long-Term Safety and Efficacy of upadacitinib.
Study design
This is a Phase 3, multicenter, long-term extension (LTE) study which comprises
an up to 288-week follow up period (with the option of continued treatment
dependent on country specific regulatory approval and local requirements)
designed to evaluate the long-term safety and efficacy of upadacitinib
Intervention
All subjects receive upadacitinib tablets (oral) once a day, until end of study
or discontinuation.
Study burden and risks
Upadacitinib is a novel JAK1 selective inhibitor with minimal inhibitory
effects on JAK2 and JAK3, which could potentially minimize some of the reported
safety concerns with non-selective JAK inhibition which are thought to be
mediated by inhibition of JAK2 and JAK3 signaling pathways. Upadacitinib was
tested in two studies in patients with RA. Upadacitinib was generally
well-tolerated and the types and frequencies of side-effects were typical of
patients treated with traditional RA medications. The most common reported AEs
were: headache, upper chest infection, common cold, back pain, diarrhea, and
cough. This Phase 3 long-term extension Study M14-533 will assess the long-term
safety and efficacy of upadacitinib in subjects with UC who participated in the
Phase 2b/3 Study M14-234 or Phase 3 Study M14-675. The possible clinical
improvement outweighs the risks mentioned above as well as the limited
additional study activities over a period of 288 weeks (doctor visits, blood
drawings, questionnaires and medication diary). Additionally, subjects are
closely monitored for any AEs and their relationship to the study drug will be
evaluated by the investigator, documented and analyzed.
Wegalaan 9
Hoofddorp 2132 JD
NL
Wegalaan 9
Hoofddorp 2132 JD
NL
Listed location countries
Age
Inclusion criteria
1. Subject has not responded at the end of the induction period (Week 8) in
study M14-234 (substudie 1), who has been an inadequate responder during the
maintenance period of study M14-234 (Substudy 3), or who has responded and
successfully completed study M14-234.
During the COVID-19 pandemic, for subjects with missing endoscopy due to the
COVID-19 pandemic in studies M14-234 SS2, SS3 and M14-675 those following
subjects may be enrolled if the below criteria is met:
* Subjects who achieved clinical response defined by Partial Adapted Mayo Score
at Week 8 of Studies M14-234 SS2 and M14-675
* Subjects who achieved clinical response defined by Partial Adapted Mayo Score
at Week 16 in the extended treatment period of Studies
M14-234 SS2 and M14-675
Note: If endoscopy is missing at Week 8 but can be performed at Week 16, Week
16 endoscopy should be performed. However, the status of
clinical response will be defined by Partial Adapted Mayo Score and clinical
responders may enter Study M14-533 Cohort 1.
* Subjects who have completed the 52-week treatment in Study M14-234 SS3 if the
PI considers it is safe to continue based on phone/video
call, subject's medical history and findings from the last endoscopy.
2. Women of childbearing potential (refer to section 5.2.4 of the protocol)
must have a negative urine pregnancy test at Week 0 visit.
3. If female, subject must meet the contraception criteria.
4. Subject is judged to be in otherwise good health as determined by the
principal investigator based upon clinical evaluations performed during the
preceding studies.
5. Must be able and willing to give written informed consent and to comply with
the requirements of this study protocol.
Exclusion criteria
1. For any reason subject is considered by the investigator to be an unsuitable
candidate.
2. Female subject with a positive pregnancy test at Baseline (final visit of
the preceding studies) or who is considering becoming pregnant during the study
and within 30 days after the last dose of study drug.
3. Known hypersensitivity to upadacitinib or its excipients or had any adverse
event (AE) during the preceding studies, that in the investigator's judgment
makes the participant unsuitable for this study
4. Subject with an active or recurrent infection that based on the
investigator's clinical assessment makes the subject an unsuitable candidate
for the study. Subjects with ongoing infections undergoing treatment may be
enrolled BUT NOT dosed until the infection has been successfully treated.
5. Current evidence of active tuberculosis; Current evidence of latent
tuberculosis and for any reason the subject cannot take full course of TB
prophylaxis treatment
6. Subject with a poorly controlled medical condition, such as uncontrolled
diabetes, unstable ischemic heart disease, moderate or severe congestive heart
failure, recent cerebrovascular accidents and any other condition which, in the
opinion of the investigator or sponsor, would put the subject at risk by
participation in this study.
Design
Recruitment
Medical products/devices used
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
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 | CTIS2023-505699-31-00 |
| EudraCT | EUCTR2016-000674-38-NL |
| CCMO | NL58325.018.16 |