Clinical trial NCT06249555: VOICE-Early Response to Vedolizumab and IL-23 Antagonists in Participants With Crohn's Disease: A Prospective Observational Study
Official title: VOICE-Characterization of Early Response to Vedolizumab and IL-23 Antagonists in Participants With Crohn's Disease Using Patient-Reported Outcome Measures: A Prospective Observational Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Crohn's Disease
Keywords: Vedolizumab
Ustekinumab
Patient reported outcome
IL-23 antagonists
Risankizumab
Lead sponsor: Alimentiv Inc.
Sponsor class: OTHER
Collaborators: name: Takeda
First posted: 2024-02-08
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will be conducted in US and Canadian participants with CD prescribed VDZ or IL-23 antagonists for the first time. Approximately 300 participants with CD who are initiating first-time treatment with VDZ or UIL-23 antagonists will be enrolled in this study.

Brief summary: The primary aim of this study is to explore the time course of response to Vedolizumab in participants with CD as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference-short form (SF), as well as other PROMIS domain SFs (fatigue, anxiety, depression, sleep disturbance, physical function, and ability to participate in social roles and activities); other PRO measures will also be assessed.

Detailed description: Vedolizumab (VDZ), a monoclonal antibody that selectively targets intestinal T-cell trafficking, is an effective and safe treatment for moderately to severely active Crohn's disease (CD). Recent evidence from open-label, blinded endpoint studies such as VERSIFY and LOVE-CD provide further support for the efficacy of VDZ in achieving clinical, endoscopic, histologic and radiologic disease improvement in CD. Despite these data, VDZ is generally perceived to have a slower onset of action than other biologics, including tumor necrosis factor (TNF) antagonists and the interleukin (IL)-12/23 antagonist, ustekinumab (UST). The IL-23 antagonist risankizumab (RISA) has been more recently approved for treatment of CD and post-hoc analyses of SEQUENCE trial data showed RISA to be superior to UST for inducing clinical remission at Week 24, and thus, RISA may also be considered to have a quicker onset of action than VDZ. This perception largely emanates from the results of the VDZ pivotal for CD (GEMINI 2) where efficacy was assessed at Week 6 after only 2 doses in a largely refractory population. However, in clinical practice VDZ induction consists of 3 doses of VDZ 300 mg administered intravenously at weeks 0, 2 and 6 instead of the 2 doses used in the pivotal trials. In recent clinical trials, induction endpoints for therapeutics in CD are now typically measured at least after Week 12. Accordingly, it is uncertain whether the generally held perception of a relatively slow onset of action for VDZ is accurate. Moreover, it should also be noted that the perception of a slow onset of action has also been conflated to infer that VDZ is a relatively less effective induction therapy in CD than TNF antagonists or UST. Further data to evaluate these issues are needed.

Rapidity of symptom resolution, which is commonly used as a surrogate for speed of onset, is a priority for patients and clinicians. It is therefore important to better understand the kinetics of symptom improvement captured using patient-reported outcomes (PROs) in patients initiating VDZ for treatment of CD.

Eligibility criteria: Inclusion Criteria:

1. Participant is an adult 18 years of age or older with confirmed CD, as per standard clinical criteria which may include symptoms, endoscopy, histopathology, and imaging.
2. Participant has active CD and has been prescribed as standard of care (SOC) and is planned to start VDZ or IL-23 antagonist therapy (UST, RISA, or GUS or MIR \[if approved for the treatment of CD during the recruitment period for this study\]) for the first time in accordance with the product label, as determined by the treating physician.
3. Participant has a baseline PROMIS Pain Interference-SF score ≥ 15 (corresponding T-score ≥ 55) (PROMIS Pain Interference-SF 8a \[V1.1\]).

   a. Score is calculated by adding score (1 to 5) for each of the 8 subcomponents.
4. Participant has completed all SOC biologic work-up assessments (this may include assessment of tuberculosis, chronic infections, Clostridioides difficile infection and vaccination status per local practice).
5. Ability of participant to participate fully in all aspects of this observational study. Full comprehension of consent language and informed consent must be obtained from the participant and documented.

Exclusion Criteria:

1. Participant has CD-related surgery planned or anticipated during the study.
2. Participant has prior exposure to an advanced therapy for the treatment of CD (biologic or small molecule) other than an anti-TNF (i.e., anti-integrin, anti-IL, Janus kinase inhibitors, or sphingosine-1-phosphate receptor 1). Prior failure or intolerance to 2 or more anti-TNF (i.e., infliximab, adalimumab, or certolizumab pegol) therapies in the past 3 years is also cause for exclusion.
3. Participant has an active infection at baseline requiring intravenous systemic antibiotics.

   Note: The treating physician must have completed all appropriate baseline screening tests as per the product label.
4. Participant has evidence of C. difficile toxin or is prescribed treatment for C. difficile infection, or other intestinal bacterial pathogen, ≤ 2 weeks prior to Screening.
5. Participant has chronic non-inflammatory bowel disease pain.

Primary outcomes:
measure: To assess time of onset of biologic therapy in pain interference
timeFrame: Baseline to Week 14
Secondary outcomes:
measure: To assess time of onset of biologic therapy in multiple QOL and functioning domains
timeFrame: Baseline to Weeks 14, 30, and 52
measure: To assess the efficacy of therapy in inducing a meaningful clinical improvement in pain interference through Week 52 through a reduction in PROMIS - Pain Interference - Short Form Scores.
timeFrame: Baseline to Weeks 14, 30, and 52
measure: To assess the efficacy of therapy in inducing a meaningful clinical improvement in fatigue through Week 52 through a reduction in PROMIS - Fatigue - Short Form Scores.
timeFrame: Baseline to Weeks 14, 30, and 52
measure: To assess the efficacy of therapy in inducing a meaningful clinical improvement in anxiety through Week 52 through a reduction in PROMIS - Emotional Distress - Anxiety - Short Form Scores.
timeFrame: Baseline to Weeks 14, 30, and 52
measure: To assess the efficacy of therapy in inducing a meaningful clinical improvement in depression through Week 52 through a reduction in PROMIS Emotional Distress - Depression - Short Form.
timeFrame: Baseline to Weeks 14, 30, and 52
measure: To assess the efficacy of therapy in inducing a meaningful clinical improvement in sleep disturbance through Week 52 through a reduction in PROMIS - Sleep Disturbance - Short Form.
timeFrame: Baseline to Weeks 14, 30, and 52
measure: To assess the efficacy of therapy in inducing a meaningful clinical improvement in physical function through Week 52 through a reduction in PROMIS - Physical Function - Short Form.
timeFrame: Baseline to Weeks 14, 30, and 52
measure: To assess the efficacy of therapy in inducing a meaningful clinical improvement in ability to participate in social roles and activities through Week 52 through a reduction in PROMIS - Ability to Participate in Social Roles and Activities - Short Form.
timeFrame: Baseline to Weeks 14, 30, and 52
measure: To assess early change in patient-reported symptoms within the PRO-2 through Week 14.
timeFrame: Baseline to Week 14
measure: To assess early change in patient-reported symptoms within the PROMIS - Pain Interference - Short Form through Week 14
timeFrame: Baseline to Week 14
measure: To assess early change in patient-reported symptoms within the PROMIS - Fatigue - Short Form through Week 14
timeFrame: Baseline to Week 14
measure: To assess early change in patient-reported symptoms within the PROMIS - Anxiety - Short Form through Week 14
timeFrame: Baseline to Weeks 2, 6 and 14
measure: To assess early change in patient-reported symptoms within the PROMIS - Depression - Short Form through Week 14
timeFrame: Baseline to Weeks 2, 6 and 14
measure: To assess early change in patient-reported symptoms within the PROMIS - Sleep Disturbance - Short Form through Week 14
timeFrame: Baseline to Weeks 2, 6 and 14
measure: To assess early change in patient-reported symptoms within the PROMIS - Physical Function - Short Form through Week 14
timeFrame: Baseline to Weeks 2, 6 and 14
measure: To assess early change in patient-reported symptoms within the PROMIS - Ability to Participate in Social Roles and Activities - Short Form through Week 14
timeFrame: Baseline to Weeks 2, 6 and 14
measure: To evaluate the association between the PRO-2 and each PROMIS domain
timeFrame: Baseline to Weeks 14, 30, and 52
measure: To assess the efficacy of therapy in resolving patient-reported symptoms by obtaining PRO-2 clinical remission, defined as a stool frequency score ≤ 3 and abdominal pain score ≤ 1 using unweighted subscores through week 52.
timeFrame: Baseline to Weeks 2, 6, 14, 22, 30, 38, 46, and 52
measure: To assess the efficacy of therapy in resolving patient-reported symptoms by obtaining PRO-2 clinical response, defined as a decrease in the weighted PRO-2 of ≥ 50% from baseline through week 52.
timeFrame: Baseline to Weeks 2, 6, 14, 22, 30, 38, 46, and 52
measure: To assess the efficacy of therapy in resolving fecal urgency defined by a change in UNRS scores from baseline through week 52.
timeFrame: Baseline to Weeks 2, 6, 14, 22, 30, 38, 46, and 52
measure: To assess the efficacy of therapy in resolving patient-reported symptoms and improving health related QOL as shown by SIBDQ improvement, defined as ≥ 9-point increase in the SIBDQ from baseline through week 52.
timeFrame: Baseline to Weeks 2, 6, 14, 22, 30, 38, 46, and 52
measure: To assess the efficacy of therapy in resolving patient-reported symptoms and improving health related QOL as shown by obtaining SIBDQ remission, defined as an SIBDQ score ≥ 60 through week 52.
timeFrame: Baseline to Weeks 2, 6, 14, 22, 30, 38, 46, and 52
measure: To assess the durability of symptom improvement
timeFrame: Baseline to Week 14
measure: To assess the efficacy of therapy in resolving patient-reported symptoms by obtaining PRO-2 clinical response through week 52.
timeFrame: Baseline to Weeks 2, 6, 14, 22, 30, 38, 46, and 52
Other outcomes:
Locations:
city: Sun City
country: United States
facility: GI Alliance - Sun City
state: Arizona
city: Kissimmee
country: United States
facility: Digestive and Liver Center of Florida
state: Florida
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: New Orleans
country: United States
facility: University Medical Center New Orleans
state: Louisiana
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Portland
country: United States
facility: OR Clinic - East - GI
state: Oregon
city: Fort Worth
country: United States
facility: GI Alliance Research Fort Worth
state: Texas
city: Mansfield
country: United States
facility: GI Alliance Research Mansfield
state: Texas
city: Bellevue
country: United States
facility: GI Alliance - Bellevue - Washington Gastroenterology
state: Washington
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Brampton
country: Canada
facility: GNRR Digestive Clinics and Research Center
state: Ontario
city: London
country: Canada
facility: Alimentiv
state: Ontario
city: Mississauga
country: Canada
facility: West GTA Research Inc.
state: Ontario
city: Oakville
country: Canada
facility: Rajbir Rai Medicine Professional Corporation
state: Ontario
city: Oakville
country: Canada
facility: ABP Research Services Corp.
state: Ontario
city: Scarborough
country: Canada
facility: Scarborough Center for Inflammatory Bowel Disease
state: Ontario
city: Toronto
country: Canada
facility: Toronto Immune & Digestive Health Institute Inc.
state: Ontario
city: Hamilton
country: Canada
facility: McMaster University Medical Center
state: Ontatrio
Study officials:
References: