The main objective of Study M15-722 is to characterize the efficacy, safety, and tolerability of ravagalimab (ABBV-323) as induction treatment in subjects with moderately to severely active UC.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint for Study M15-722 is the proportion of subjects with
endoscopic improvement (Mayo endoscopic subscore of 0 or 1) at Week 8.
Secondary outcome
Secondary Endpoints for Induction Period (Weeks 0 to 12)
- Proportion of subjects with clinical remission per Adapted Mayo score at Week
8
- Proportion of subjects with clinical response per Adapted Mayo score at Week
8
- Proportion of subjects with clinical response per Partial Adapted Mayo score
over time
- Proportion of subjects with clinical remission per Full Mayo score at Week 8
in subjects with a Full Mayo score of 6 to 12 at Baseline
- Proportion of subjects with endoscopic remission at Week 8
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 of UC 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.
Ravagalimab (ABBV-323) is a monoclonal antibody that works by antagonizing
CD40. CD40 is a tumor necrosis factor (TNF) receptor family member that plays
an important role in lymphocyte activation and antigen presenting cell (APC)
function.
Study objective
The main objective of Study M15-722 is to characterize the efficacy, safety,
and tolerability of ravagalimab (ABBV-323) as induction treatment in subjects
with moderately to severely active UC.
Study design
Study M15-722 is a Phase 2a, multicenter, single arm, open-label studydesigned
to evaluate the efficacy and safety of intravenous and subcutaneous
administration of ravagalimab (ABBV-323) as induction therapy for 12 weeks in
subjects with moderately to severely active UC.
At the end of week 12, if subjects have a clinical response, they may continue
to receive ravagalimab (ABBV-323) in the 92-week maintenance portion of the
study.
Intervention
Participants administered with ravagalimab (ABBV-323) dose A IV and ravagalimab
(ABBV-323) dose B for 12 Weeks. Participants who achieve clinical response may
enter the maintenance period in which participants are administered with
ravagalimab (ABBV-323) dose B.
Study burden and risks
There will be higher burden for subjects participating in this study compared
to their standard of care. Subjects will be visiting the clinic more
frequently. During these visits study procedures will be performed including
blood sampling and endoscopies. Subjects will be tested for TB, Hepatitis
C/Hepatitis B and HIV. Women of childbearing potential must practice a method
of birth control during the study through at least 84 days after the last dose
of study drug and will be tested for pregnancy.
Ravagalimab (ABBV-323) has not been studied before in subjects with ulcerative
colitis. Studies in healthy volunteers showed that ravagalimab (ABBV-323) was
well tolerated and that there were no identified safety concerns. Side effects
for drugs that work in a similar way as ravagalimab (ABBV-323) are: serious
infections such as hepatitis, pneumonia, cellulitis, urinary tract infection,
diverticulitis and shingles; opportunistic infections such as tuberculosis,
fungal and viral infections; lab test abnormalities such as elevated liver
function tests.
Wegalaan 9
Hoofddorp 2132 JD
NL
Wegalaan 9
Hoofddorp 2132 JD
NL
Listed location countries
Age
Inclusion criteria
· Subjects must voluntarily sign and date an informed consent, approved by an
independent ethics committee (IEC)/institutional review board (IRB), prior to
the initiation of any screening or study-specific procedures.
· Adult male or female, between 18 and 75 years of age, inclusive, at time of
the Baseline visit.
· Diagnosis of UC for at least 3 months prior to Baseline. Appropriate
documentation of biopsy results consistent with the diagnosis of UC or in the
assessment of the Investigator, must be available.
· Subject meets the following disease activity criteria: Active UC with an
Adapted Mayo score of 5 to 9 points and endoscopic subscore of 2 to 3
(confirmed by central review).
· History of inadequate response, loss of response, or intolerance to one or
more of the approved biologic therapies: infliximab, adalimumab, golimumab,
vedolizumab, and/or tofacitinib (Note: If tofacitinib was received in a
clinical trial, subject must have received open-label drug).
- Laboratory values meeting the following criteria:
Serum aspartate transaminase (AST) and alanine transaminase (ALT) <= 2 × upper
limit of
normal (ULN);Total white blood cell (WBC) count >= 3.0 × 109 /L;
Exclusion criteria
- Subject must not have an active, chronic, or recurrent infection that based
on the Investigator's clinical assessment makes the subject an unsuitable
candidate for the study
- Subject must not have any malignancy except for successfully treated non
metastatic cutaneous squamous cell or basal cell carcinoma or localized
carcinoma in situ of the cervix.
- Subject must not have history of dysplasia of the gastrointestinal tract or
evidence of dysplasia in any biopsy performed during the Screening endoscopy
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 |
|---|---|
| EudraCT | EUCTR2018-000930-37-NL |
| CCMO | NL67056.028.18 |