This study has been transitioned to CTIS with ID 2023-504736-18-00 check the CTIS register for the current data. Primary Objectives (Phase 2 and Phase 3):- To evaluate the clinical efficacy of guselkumab in participants with Crohn*s disease- To…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary End Point:
Phase 2: Change from baseline in the Crohn's Disease Activity Index (CDAI)
Score at Week 12.
Phase 3:
- Clinical remission at Week 12 (defined as CDAI score <150)
- Endoscopic response at Week 12
Secondary outcome
Secondary End Point:
Phase 2:
- Clinical remission at Week 12 (defined as CDAI score <150)
- Clinical response at Week 12 (defined as >=100-point reduction from baseline
in CDAI score or CDAI score <150)
- PRO-2 remission at Week 12 (defined based on average daily stool frequency
(SF) and average daily abdominal pain (AP) score)
- Clinical-biomarker response at Week 12 (clinical response based on CDAI score
and reduction from baseline in CRP or fecal calprotectin)
- Endoscopic response at Week 12 (measured by the Simple Endoscopic Score for
Crohn's Disease (SES-CD). The SES-CD is based on the evaluation of 4 endoscopic
components across 5 ileocolonic segments, with a total score ranging from 0 to
56.)
Phase 3:
- Clinical remission at Week 48 (defined as CDAI < 150)
- Durable clinical remission at Week 48 (defined as CDAI<150 for the majority
of visits between Week 12 and Week 48.)
- Corticosteroid-free clinical remission at Week 48 (defined as CDAI score <150
at Week 48 and not receiving corticosteroids at Week 48)
- PRO-2 remission at Week 12 and 48 (based on average daily stool frequency
(SF) and average daily abdominal pain (AP) score)
- Endoscopic response at Week 48 (measured by the Simple Endoscopic Score for
Crohn's Disease (SES-CD))
· Fatigue response at Week 12 (based on the PROMIS Fatigue Short Form 7a)
- Endoscopic remission at Week 12 and Week 48
Background summary
Currently, there are 3 classes of biologic agents approved for the treatment of
moderately to severely active Crohn*s disease: tumor necrosis factor (TNF)
antagonist therapies (infliximab, adalimumab, certolizumab), integrin
inhibitors (natalizumab and vedolizumab), and IL-12/23 inhibitors
(ustekinumab). Although the introduction of biologic agents has significantly
improved the clinical management of patients with moderately to severely active
Crohn*s disease, a sizable proportion of the target patient population is
non-responsive or will lose response over time. A review of the available data
for approved biologic agents highlighted the unmet need in achieving and
maintaining long-term remission, especially among patients who have previously
failed biologic treatments. Therefore, there remains a high unmet need for new
treatment options in Crohn*s disease that are safe and effective, especially
new therapies that can provide improved long-term efficacy (ie, sustained
remission) over currently available therapies.
Genetic and animal model studies have explored the contribution of IL-12 and
IL-23 in driving the pathophysiology of Crohn*s disease. The results indicate
that IL-23 plays a predominant role in inflammatory bowel disease (IBD) and
emerging evidence suggests that blocking IL-23 alone may be a more effective
strategy than blocking both IL-12 and IL-23. Clinical studies have successfully
demonstrated that blockade of both IL-12 and IL-23 is effective in treating
Crohn*s disease, leading to the approval of ustekinumab (STELARA) most
recently. However, it has yet been determined whether targeting both IL-12/23
compared with specifically targeting of IL-23 alone, is a more effective
treatment strategy clinically. Hence, the purpose of this protocol is to
evaluate the efficacy and safety of guselkumab, a monoclonal antibody to IL-23,
compared with placebo and compared an approved treatment for CD, ustekinumab (a
monoclonal antibody to IL-12/23), in participants with Crohn*s disease.
Study objective
This study has been transitioned to CTIS with ID 2023-504736-18-00 check the CTIS register for the current data.
Primary Objectives (Phase 2 and Phase 3):
- To evaluate the clinical efficacy of guselkumab in participants with Crohn*s
disease
- To evaluate the safety of guselkumab
Secondary Objectives:
Phase 2:
- To evaluate the dose-response of guselkumab to inform dose selection for the
Phase 3 portion of this protocol
- To evaluate the efficacy of guselkumab on endoscopic improvement
- To evaluate the pharmacokinetics (PK), immunogenicity, and pharmacodynamics
(PD) of guselkumab therapy
Phase 3:
- To evaluate the efficacy of guselkumab on endoscopic improvement
- To evaluate the impact of guselkumab on HRQOL
- To evaluate the PK, immunogenicity, and PD of guselkumab therapy
Study design
This is a Phase 2/3, Randomized, Double-blind, Placebo- and Active-controlled,
Parallel-group, Multicenter Protocol. This protocol consists of 3 separate
studies: a 48-week Phase 2 dose-ranging study (GALAXI 1) and two 48-week Phase
3 confirmatory studies (GALAXI 2 and GALAXI 3). In Phase 2, safety and efficacy
of guselkumab dose regimens will be evaluated to support the selection of
induction and maintenance dose regimens for confirmatory evaluation in Phase 3.
Participants who complete the 48-week Phase 2 or Phase 3 studies may be
eligible to enter the long-term extension (LTE). Approximately 1340
participants will be enrolled into this protocol globally. Throughout the 3
studies, efficacy, pharmacokinetic, biomarkers, and safety will be assessed. An
external Independent Data Monitoring Committee (DMC), with defined roles and
responsibilities as governed by a DMC charter, will assess the safety of
participants enrolled under this protocol. After each review of safety data,
they will make recommendations to the sponsor about the continuation of the
protocol.
Intervention
*Phase 2 treatment groups:*
Phase 2 (GALAXI 1): Group 1 (Guselkumab):
Participants will receive guselkumab (Dose 1) by intravenous infusion, followed
by guselkumab (Dose 2) by subcutaneous (SC) injection. Participants who are
eligible and willing to continue guselkumab may enter the Long-Term Extension
(LTE) phase and continue to receive guselkumab.
Phase 2 (GALAXI 1): Group 2 (Guselkumab):
Participants will receive guselkumab (Dose 3) by intravenous (IV) infusion,
followed by guselkumab (Dose 2) by subcutaneous (SC) injection. Participants
who are eligible and willing to continue guselkumab may enter the LTE phase and
continue to receive guselkumab.
Phase 2 (GALAXI 1): Group 3 (Guselkumab):
Participants will receive guselkumab (Dose 4) by intravenous (IV) infusion,
followed by guselkumab (Dose 5) by subcutaneous (SC) injection. Participants
who are eligible and willing to continue guselkumab may enter the LTE phase and
continue to receive guselkumab.
Phase 2 (GALAXI 1): Group 4 (Ustekinumab):
Participants will receive ustekinumab by intravenous (IV) infusion, followed by
subcutaneous (SC) injection. Participants who are eligible and willing to
continue ustekinumab may enter the LTE and continue to receive ustekinumab.
Phase 2 (GALAXI 1): Group 5 (Placebo/Ustekinumab):
Participants will receive placebo administered by intravenous (IV) infusion. At
Week 12, non-responders will receive active treatment (Ustekinumab)
administered by intravenous (IV) infusion followed by subcutaneous (SC)
injection. Participants who are eligible and willing to continue
placebo/ustekinumab may enter the LTE and continue to receive
placebo/ustekinumab.
*Phase 3 treatment groups*
Phase 3 (GALAXI 2 and 3): Group 1 and Group 2 (Guselkumab):
Participants will receive guselkumab by intravenous (IV) infusion, followed by
guselkumab by subcutaneous (SC) injection. Participants who are eligible and
willing to continue guselkumab may enter the LTE phase and continue to receive
guselkumab.
Note: Guselkumab dose regimens for Phase 3 evaluation will be determined based
on the results of the Phase 2 study.
Phase 3 (GALAXI 2 and 3): Group 3 (Ustekinumab):
Participants will receive ustekinumab by intravenous (IV) infusion, followed by
subcutaneous (SC) injection. Participants who are eligible and willing to
continue ustekinumab may enter the LTE phase and continue to receive
ustekinumab.
Phase 3 (GALAXI 2 and 3): Group 4 (Placebo/Ustekinumab):
Participants will receive placebo administered by intravenous (IV) infusion. At
Week 12, non-responders will receive active treatment (ustekinumab)
administered by intravenous (IV) infusion followed by subcutaneous (SC)
injection. Participants who are eligible and willing to continue
placebo/ustekinumab may enter the LTE and continue to receive
placebo/ustekinumab.
Study burden and risks
In general, study participants may experience physical or psychological
discomfort from the study tests, study procedures, interviews and
questionnaires; and each study participant may have a different experience. In
addition, study particpants may experience side effects from the study
medication. For a discussion of the Sponsor*s benefit-risk assessment please
refer to Section 2.3 of the Protocol.
Number of visits:
-Max 39 over the course of study participation
Chest X-ray: 1 time at screening.
ECG: 1 time at screening.
Blood draws for efficacy, safety, biomarkers etc. evaluation: max 41 over
course of study participation.
QuantiFERON-TB blood test: 1 time at screening; additional testing may apply if
necessary due to initial findings.
Urine test for pregnancy: Urine pregnancy test for females of childbearing
potential before each study intervention (max 38 visits).
Video Ileocolonoscopy with Biopsies: max 4 times for all participants over
course of study participation. 1 additional optional time point for
participants who consent to the sub-study.
Physical examination: max. 39 times over course of study participation.
Interviews and questionnaires: max 39 over course of study participation
Stool samples for screening eligibility and biomarkers: max 14 over course of
study participation
Fistula assessment: max 27 times.
Turnhoutseweg 30
Beerse 2340
BE
Turnhoutseweg 30
Beerse 2340
BE
Listed location countries
Age
Inclusion criteria
Have screening laboratory test results within the protocol specified
parameters; Female participants of childbearing potential must have a negative
urine pregnancy test result at screening and baseline; Participants must have
demonstrated intolerance or inadequate response to conventional or to biologic
therapy for CD.
Exclusion criteria
Current diagnosis of ulcerative colitis or indeterminate colitis; Has
complications of Crohn*s disease, such as symptomatic strictures or stenoses,
short gut syndrome, or any other manifestation; On unstable doses of
concomitant Crohn's disease therapy; Receipt of Crohn*s disease approved
biologic agents, investigational agents, or procedures outside of permitted
timeframe as specified in the protocol; Prior exposure to p40 inhibitors or p19
inhibitors; Any medical contraindications preventing study participation;
During the 6 weeks prior to baseline, have had ANY of (a) confirmed SARS-CoV-2
(COVID-19) infection (test positive), OR (b) suspected SARS-CoV-2 infection
(clinical features without documented test results), OR (c) close contact with
a person with known or suspected SARS-CoV-2 infection (see Protocol Appendix
27Apr2020 for exceptions and notes).
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 |
|---|---|
| Other | clintrials.gov. NCT number is NCT03466411 |
| EU-CTR | CTIS2023-504736-18-00 |
| EudraCT | EUCTR2017-002195-13-NL |
| CCMO | NL64944.028.18 |