VOICE-Early Response to Vedolizumab and Ustekinumab in Participants With Crohn's Disease: A Prospective Observational Study (VOICE)

VOICE-Characterization of Early Response to Vedolizumab and Ustekinumab in Participants With Crohn's Disease Using Patient-Reported Outcome Measures: A Prospective Observational Study

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: Vedolizumab (VDZ); Drug: Ustekinumab (UST)

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 ustekinumab (UST). 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.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Susan Archer; Phone Number: 226-919-6959; Email: susan.archer@alimentiv.com
• Study Contact Backup: Name: Heather MacAulay; Email: heather.macaulay@alimentiv.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study will be conducted in US and Canadian participants with CD prescribed VDZ or UST for the first time. Approximately 300 participants with CD who are initiating first-time treatment with VDZ or UST will be enrolled in this study.

Description

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 UST therapy 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 PI-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, Clostridium 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 (biologic or small molecule) other than an anti-TNF (i.e., anti-integrin, anti-interleukin). Prior failure of >1 anti-TNF (i.e., infliximab, adalimumab, or certolizumab pegol) therapy 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 Clostridium 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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Vedolizumab; Group one will include participants who will be starting Vedolizumab as part of routine care. Dose, frequency and duration are not mandated as part of the study and are determined by the health care provider.	Drug: Vedolizumab (VDZ); Participants will receive VDZ as part of routine care.; Other Names: Entyvio
Ustekinumab; Group two will include participants who will be starting Ustekinumab as part of routine care. Dose, frequency and duration are not mandated as part of the study and are determined by the health care provider.	Drug: Ustekinumab (UST); Participants will receive UST as part of routine care.; Other Names: Stelara

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess time of onset of biologic therapy in pain interference	Time to meaningful clinical improvement in pain interference, defined as a ≥ 2-point decrease in the PROMIS Pain Interference-SF T-score	Baseline to Week 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess time of onset of biologic therapy in multiple QOL and functioning domains	Time to meaningful clinical improvement for each individual PROMIS domain, defined as a ≥ 2-point change in the direction of improvement in the respective PROMIS domain T-score (Note: A higher PROMIS domain T-score represents more of the concept being measured. For the Ability to Participate in Social Roles and Activities domain an increase in T-score	Baseline to Weeks 14, 30, and 52
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.	Meaningful clinical improvement in each individual PROMIS domain at Weeks 14, 30, and 52	Baseline to Weeks 14, 30, and 52
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.	Meaningful clinical improvement in each individual PROMIS domain at Weeks 14, 30, and 52	Baseline to Weeks 14, 30, and 52
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.	Meaningful clinical improvement in each individual PROMIS domain at Weeks 14, 30, and 52	Baseline to Weeks 14, 30, and 52
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.	Meaningful clinical improvement in each individual PROMIS domain at Weeks 14, 30, and 52	Baseline to Weeks 14, 30, and 52
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.	Meaningful clinical improvement in each individual PROMIS domain at Weeks 14, 30, and 52	Baseline to Weeks 14, 30, and 52
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.	Meaningful clinical improvement in each individual PROMIS domain at Weeks 14, 30, and 52	Baseline to Weeks 14, 30, and 52
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.	Meaningful clinical improvement in each individual PROMIS domain at Weeks 14, 30, and 52	Baseline to Weeks 14, 30, and 52
To assess early change in patient-reported symptoms within the PRO-2 through Week 14.	Change in PRO-2 (liquid/very soft stool frequency + abdominal pain) from baseline to Week 14.	Baseline to Week 14
To assess early change in patient-reported symptoms within the PROMIS - Pain Interference - Short Form through Week 14	Change in PROMIS Pain Interference-SF from baseline to Week 14.	Baseline to Week 14
To assess early change in patient-reported symptoms within the PROMIS - Fatigue - Short Form through Week 14	Change in PROMIS Fatigue-SF scores from baseline to Week 14.	Baseline to Week 14
To assess early change in patient-reported symptoms within the PROMIS - Anxiety - Short Form through Week 14	Change in PROMIS Anxiety-SF-scores from baseline to Weeks 2, 6, and 14.	Baseline to Weeks 2, 6 and 14
To assess early change in patient-reported symptoms within the PROMIS - Depression - Short Form through Week 14	Change in PROMIS Depression- SF-scores from baseline to Weeks 2, 6, and 14.	Baseline to Weeks 2, 6 and 14
To assess early change in patient-reported symptoms within the PROMIS - Sleep Disturbance - Short Form through Week 14	Change in PROMIS Sleep Disturbance- SF-scores from baseline to Weeks 2, 6, and 14.	Baseline to Weeks 2, 6 and 14
To assess early change in patient-reported symptoms within the PROMIS - Physical Function - Short Form through Week 14	Change in PROMIS Physical Function- SF-scores from baseline to Weeks 2, 6, and 14.	Baseline to Weeks 2, 6 and 14
To assess early change in patient-reported symptoms within the PROMIS - Ability to Participate in Social Roles and Activities - Short Form through Week 14	Change in PROMIS Ability to Participate in Social Roles and Activities- SF-scores from baseline to Weeks 2, 6, and 14.	Baseline to Weeks 2, 6 and 14
To evaluate the association between the PRO-2 and each PROMIS domain	Correlation between PRO-2 scores and each individual PROMIS domain T-score • Correlation between change in PRO-2 scores and change in each individual PROMIS domain T-score	Baseline to Weeks 14, 30, and 52
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.	SIBDQ improvement (defined as ≥ 9-point increase in the SIBDQ from baseline) at Weeks 2, 6, 14, 22, 30, 38, 46, and 52	Baseline to Weeks 2, 6, 14, 22, 30, 38, 46, and 52
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.	Assess the efficacy of therapy in resolving patient-reported symptoms and fecal urgency, and improving health-related QOL through Week 52	Baseline to Weeks 2, 6, 14, 22, 30, 38, 46, and 52
To assess the efficacy of therapy in resolving fecal urgency defined by a change in UNRS scores from baseline through week 52.	SIBDQ remission (defined as an SIBDQ score ≥ 60) at Weeks 2, 6, 14, 22, 30, 38, 46, and 52	Baseline to Weeks 2, 6, 14, 22, 30, 38, 46, and 52
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.	PRO-2 clinical response (defined as a decrease in the weighted PRO-2 of ≥ 50% from baseline) at Weeks 2, 6, 14, 22, 30, 38, 46, and 52	Baseline to Weeks 2, 6, 14, 22, 30, 38, 46, and 52
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.	PRO-2 clinical remission (defined as a stool frequency score ≤ 3 and abdominal pain score ≤ 1 using unweighted subscores) at Weeks 2, 6, 14, 22, 30, 38, 46, and 52	Baseline to Weeks 2, 6, 14, 22, 30, 38, 46, and 52
To assess the durability of symptom improvement	PRO-2 clinical remission at Week 52 among participants who had PRO-2 clinical remission at Week 14	Baseline to Week 14

Collaborators and Investigators

• Sponsor: Alimentiv Inc.
• Collaborators: Takeda

Study record dates

Study Major Dates

• Study Start (Estimated): March 31, 2024
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: January 24, 2024
• First Submitted That Met QC Criteria: January 31, 2024
• First Posted (Actual): February 8, 2024

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Patient reported outcome; Ustekinumab; Vedolizumab
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Gastrointestinal Agents; Dermatologic Agents; Vedolizumab; Ustekinumab
• Other Study ID Numbers: TAK01796

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No