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Study of Treat to Target Versus Routine Care Maintenance Strategies in Crohn's Disease Patients Treated With Ustekinumab (STARDUST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03107793
Recruitment Status : Active, not recruiting
First Posted : April 11, 2017
Last Update Posted : September 2, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag Ltd.

Brief Summary:
The purpose of this study is to evaluate the efficacy of a treat to target strategy coupled with early endoscopic assessment versus a clinically driven (routine care) approach in achieving endoscopic response.

Condition or disease Intervention/treatment Phase
Crohn Disease Drug: Ustekinumab Phase 3

Detailed Description:
Study investigates benefit of treat to target maintenance treatment strategy versus routine care to test hypothesis that 'treat to target' ustekinumab (UST) maintenance treatment strategy coupled with early endoscopic assessment will result in higher endoscopic response rate after 48 weeks of treatment, compared to pragmatic maintenance treatment strategy. It consists of screening (5 weeks); treatment period (Week 0 to 48); extension period (Weeks 48 to 104) and safety follow up visit (16 weeks after last dose). Participants will be given an option to enter ultrasound sub-study to assess intestinal ultrasound (IUS) parameters indicating transmural changes in response to treatment with UST in participants with Crohn's disease. Study treatment will be unaffected by participation in sub-study which is optional for participants of main study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Study of Treat to Target Versus Routine Care Maintenance Strategies in Crohn's Disease Patients Treated With Ustekinumab
Actual Study Start Date : April 19, 2017
Actual Primary Completion Date : April 30, 2020
Estimated Study Completion Date : July 24, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease
Drug Information available for: Ustekinumab

Arm Intervention/treatment
Experimental: All Participants
At Week (Wk) 0, all eligible participants will initiate intravenous (IV) induction treatment with ustekinumab (UST) on a weight-tiered basis at a dose of approximately 6 milligram per kilogram (mg/kg). At Week 8, all participants will receive a 90 milligram (mg) subcutaneous (SC) injection of ustekinumab. At Week 16, participants who do not achieve a Crohn's Disease Activity Index (CDAI) improvement of greater than or equal to (>=) 70 points versus Week 0 (CDAI 70) will leave the study. Remaining participants will be randomized in a 1:1 ratio to either one of two arms for open label maintenance treatment up to Week 48: the treat to target arm or the routine care arm. From Week 48, participants will continue ustekinumab treatment in the study extension period, up to Week 104. Dosing frequency will be adjusted in the extension period for the participants failing to meet the treatment target.
Drug: Ustekinumab
Participants will receive IV induction treatment with ustekinumab on a weight-tiered basis at a dose of approximately 6 milligram per kilogram (mg/kg) IV. At Week 8, all participants will receive a 90 mg SC injection of ustekinumab. During the routine care maintenance treatment period, in case of clinical worsening reported by the participant, consistent with disease flare in the investigator's judgment, clinical assessments of disease flare will be performed at the investigator's discretion.

Experimental: Routine Care Arm
In the routine care arm, assessment visits will be scheduled according to the timing of maintenance treatment injections up to Week 48, which will be in compliance with the EU SmPC for ustekinumab for the treatment of Crohn's disease, in which dosing every 12 weeks is recommended. At Week 16, (that is, 8 weeks after the first SC dose) participants continuing in the study will have demonstrated a CDAI-70 response. Nonetheless, participants who have not shown adequate response based on the investigator's judgment may receive a second SC dose at Week 16. During the routine care maintenance treatment period, in case of clinical worsening reported by the participant, consistent with disease flare in the investigator's judgment, clinical assessments of disease flare will be performed at the investigator's discretion.
Drug: Ustekinumab
Participants will receive IV induction treatment with ustekinumab on a weight-tiered basis at a dose of approximately 6 milligram per kilogram (mg/kg) IV. At Week 8, all participants will receive a 90 mg SC injection of ustekinumab. During the routine care maintenance treatment period, in case of clinical worsening reported by the participant, consistent with disease flare in the investigator's judgment, clinical assessments of disease flare will be performed at the investigator's discretion.

Experimental: Treat to Target (T2T) Arm
UST maintenance treatment assignment will be based on centrally-read colonoscopy (at Wk16). Participants with <25% improvement in SES-CD score at Wk16 will be assigned to Q8 (8-weekly) treatment and will receive UST 90mg SC at Wk16. In contrast, participants with >=25% improvement in SES-CD score at Wk16 will be assigned to Q12 treatment and will receive next UST dose (90 mg SC) at Wk20. At assessment visits (from Wk24 for participants assigned to the Q8 regimen or from Wk20 for the Q12 group) UST maintenance treatment (up to Wk 48) will be directed by T2T assessments. Participants meeting target will continue with same UST dosing frequency. The dosing frequency will be optimized for all participants failing to meet the target at assessment visit. Those previously on Q12 regimens will be adjusted to Q8 dosing; those previously on Q8 regimens will be adjusted to Q4 dosing. Participants subsequently failing to meet the target will not be able to adjust further and will leave the study.
Drug: Ustekinumab
Participants will receive IV induction treatment with ustekinumab on a weight-tiered basis at a dose of approximately 6 milligram per kilogram (mg/kg) IV. At Week 8, all participants will receive a 90 mg SC injection of ustekinumab. During the routine care maintenance treatment period, in case of clinical worsening reported by the participant, consistent with disease flare in the investigator's judgment, clinical assessments of disease flare will be performed at the investigator's discretion.

Experimental: Exploratory Extension period: From Week 48 to Week 104
At Week 48, dose de-escalation will be implemented for participants with both endoscopic remission (SES-CD score <=2) and corticosteroid-free clinical remission of at least 16 weeks duration. Participants receiving 12 weekly dosing frequency (Q12) ustekinumab will maintain this dosing frequency. Participants with either clinical remission or endoscopic remission, but not both, at Week 48 will continue with same dosing frequency or de-escalate provided maintenance of corticosteroid-free clinical remission and biomarker remission at 2 consecutive visits. Participants with neither corticosteroid-free clinical remission nor endoscopic remission will escalate dose or leave study if already on 4 weekly dosing frequency (Q4) dose. If neither clinical remission nor biomarker remission is evident at the next visit, participant will leave study. Later in the extension period, only those who achieve corticosteroid-free clinical remission and biomarker remission will undergo dose de-escalation.
Drug: Ustekinumab
Participants will receive IV induction treatment with ustekinumab on a weight-tiered basis at a dose of approximately 6 milligram per kilogram (mg/kg) IV. At Week 8, all participants will receive a 90 mg SC injection of ustekinumab. During the routine care maintenance treatment period, in case of clinical worsening reported by the participant, consistent with disease flare in the investigator's judgment, clinical assessments of disease flare will be performed at the investigator's discretion.




Primary Outcome Measures :
  1. Number of Participants With Endoscopic Response [ Time Frame: Week 48 ]
    Endoscopic Response is defined as reduction from baseline in simple endoscopic score for Crohn's disease (SES-CD) of greater than or equal to (>=) 50 percent (%). The SES-CD score is based on the evaluation of 4 endoscopic components (presence/size of ulcers, proportion of mucosal surface covered by ulcers, proportion of mucosal surface affected by any other lesions, and presence/type of narrowing/strictures) across 5 ileocolonic segments. Each endoscopic component is scored from 0 to 3 for each segment, and a total score is derived from the sum of all the component scores (range, 0 to 60).


Secondary Outcome Measures :
  1. Number of Participants With Endoscopic Remission [ Time Frame: Week 48 ]
    Endoscopic remission defined as a SES-CD score less than or equal to (<=) 2.

  2. Number of Participants With Mucosal Healing [ Time Frame: Week 48 ]
    Complete absence of mucosal ulcerations in any ileocolonic segment.

  3. Number of Participants With Clinical Remission [ Time Frame: Week 48 ]
    Clinical remission defined as a Crohn's Disease Activity Index (CDAI) score of less than (<) 150 points. The CDAI score is used to quantify the symptoms of participants with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity. In general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities.

  4. Number of Participants With Clinical Response [ Time Frame: Week 48 ]
    Clinical response defined as a >= 100 point reduction from the baseline Crohn's Disease Activity Index (CDAI) score, or a CDAI score < 150.

  5. Number of Participants With Corticosteroid-Free Clinical Remission [ Time Frame: Week 48 ]
    Clinical remission defined as a CDAI score of less than (<) 150 points.

  6. Number of Participants With Corticosteroid-Free Endoscopic Response [ Time Frame: Week 48 ]
    Corticosteroid-free endoscopic response (endoscopic response defined as a reduction from baseline in SES-CD score of >= 50%)

  7. Serum C-reactive Protein (CRP) Levels [ Time Frame: Up to Week 48 or early termination ]
    Serum CRP concentrations will be measured as a marker of the degree of inflammation.

  8. Fecal Calprotectin (FC) Levels [ Time Frame: Up to Week 48 or early termination ]
    Fecal calprotectin (FC) has been demonstrated to be a sensitive and specific marker in identifying intestinal inflammation and response to treatment in patients with Inflammatory Bowel Disease (IBD). Stool samples for FC concentrations will be collected from all participants.

  9. Percentage of Participants With a 16 - Point Change From Baseline for Inflammatory Bowel Disease Questionnaire (IBDQ) [ Time Frame: Week 48 ]
    IBDQ is a 32-item self-report questionnaire for participants with IBD to evaluate the patient-reported outcome(s) (PROs) across 4 dimensions: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Scores range from 32 to 224 with higher scores indicating better outcomes.

  10. Percentage of Participants With a 7 Point Change From Baseline in Work Productivity and Activity Impairment (WPAI) Scores for Each Domain [ Time Frame: Week 48 ]
    Work productivity was measured by the Work Productivity and Activity Impairment Questionnaire (WPAI). The WPAI is a validated, self-administered questionnaire that assesses work and activity impairment during the past 7 days. The WPAI produces 4 types of scores: absenteeism (work time missed), presenteeism (impairment at work/reduced on the job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism), and activity impairment. The WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, that is, worse outcomes.

  11. Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 48 [ Time Frame: Baseline, Week 48 ]
    IBDQ is a 32-item self-report questionnaire for subjects with IBD to evaluate the patient-reported outcome(s) (PROs) across 4 dimensions: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Scores range from 32 to 224 with higher scores indicating better outcomes.

  12. Change From Baseline in European Quality Of Life 5 Dimensions 5 Level (EQ-5D-5L) Score at Week 48 [ Time Frame: Baseline, Week 48 ]
    The EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression, using 5 levels (1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems).

  13. Changes From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) Scale at Week 48 [ Time Frame: Baseline, Week 48 ]
    FACIT-F scale is a 13 item fatigue scale with a 7 day recall period. It measures the level of fatigue during the usual daily activities. The level of fatigue is measured on a 4 point Likert scale (0=very much fatigued to 4=not at all fatigued). Total FACIT-F score is the sum of 13 items, ranging from 0 (not at all) to 52 (very much). Higher scores represent better outcomes.

  14. Change From Baseline in Hospital Anxiety and Depression Scale (HADS) at Week 48 [ Time Frame: Baseline, Week 48 ]
    HADS is a validated 14-item scale with 7 of the items relating to anxiety and 7 relating to depression. Each item is scored from 0 to 3, with higher scores indicating greater likelihood of depression or anxiety. Cases of anxiety or depression are each defined by subscale scores of 8 or greater, and categorized as normal (score of 0 to 7), mild (score of 8 to 10), moderate (score of 11 to 14), and severe (score of 15 to 21).

  15. Change from Baseline in Work Productivity and Activity Impairment (WPAI) Score at Week 48 [ Time Frame: Baseline, Week 48 ]
    The WPAI is a validated, self-administered questionnaire that assesses work and activity impairment during the past 7 days. The WPAI produces 4 types of scores: absenteeism (work time missed), presenteeism (impairment at work/reduced on the job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism), and activity impairment. The WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, that is, worse outcomes.

  16. Change From Baseline in Time Lost From Work at Week 48 [ Time Frame: Baseline, Week 48 ]
    Time lost from work represents the number of days lost from work and will be collected by asking the participants a single question, "How many days did you miss from work due to your Crohn's disease in the last 4 weeks?"

  17. Number of Participants With Adverse Events (AEs) [ Time Frame: Baseline, up to Follow-up (16 weeks after the last study drug administration) ]
    An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product and does not necessarily have a causal relationship with the treatment.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Main Study:

  • Have active, moderate to severe, ileal and/or colonic Crohn's disease, demonstrated by: baseline CDAI score of greater than or equal to (>=) 220 and less than equal to (<=) 450, and endoscopy with evidence of active Crohn's disease (defined as simple endoscopic score for Crohn's disease [SES-CD] score >=3 excluding the contribution of the narrowing component score) obtained within the 5 week screening period. A prior endoscopy may be used only if obtained within 3 months prior to baseline (Week 0), in which case the prior endoscopy must be centrally read again and SES-CD calculated based on this second, centralized read-out
  • Has had an inadequate response with, lost response to, was intolerant to, or had medical contraindications to either conventional therapy, or one previous biologic therapy approved for the treatment of Crohn's disease in the countries in which the study is conducted
  • Are eligible according to tuberculosis (TB) infection screening criteria
  • Must sign an informed consent form (ICF) or their legally acceptable representative if applicable must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.

Sub-study:

  • Be enrolled into the main study at a participating site
  • Sign a separate ICF indicating that they understand the purpose of and procedures required for this sub-study and are willing to participate in the sub-study
  • Satisfy all inclusion criteria and none of the exclusion criteria specified in the main study

Exclusion Criteria:

Main Study:

  • Has complications of Crohn's disease such as symptomatic strictures or stenoses, short gut syndrome, or any other manifestation that might be anticipated to require surgery, could preclude the use of the Crohn's Disease Activity Index (CDAI) to assess response to therapy, or would possibly confound the ability to assess the effect of treatment with ustekinumab
  • Currently has or is suspected to have an abscess. Recent cutaneous and perianal abscesses are not exclusionary if drained and adequately treated at least 3 weeks prior to baseline, or 8 weeks prior to baseline for intra-abdominal abscesses, provided there is no anticipated need for any further surgery. Participants with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses identified
  • Has had any kind of bowel resection within 6 months prior to baseline
  • Has a draining (i.e, functioning) stoma or ostomy
  • Has received more than one previous biologic therapy approved for the treatment of Crohn's disease in the countries in which the study is conducted

Sub-study:

  • Obesity or other characteristics considered likely to preclude intestinal ultrasound (IUS) visualization of the affected bowel segment
  • Normal bowel wall thickness (BWT) (that is, <=2.0 millimeter [mm] for the terminal ileum; <=3.0 mm for the colon) for all bowel segments at baseline (Week 0)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03107793


Locations
Show Show 107 study locations
Sponsors and Collaborators
Janssen-Cilag Ltd.
Investigators
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Study Director: Janssen Cilag Ltd. Clinical Trial Janssen-Cilag Ltd.
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Responsible Party: Janssen-Cilag Ltd.
ClinicalTrials.gov Identifier: NCT03107793    
Other Study ID Numbers: CR108276
2016-002918-43 ( EudraCT Number )
CNTO1275CRD3005 ( Other Identifier: Janssen-Cilag Ltd. )
First Posted: April 11, 2017    Key Record Dates
Last Update Posted: September 2, 2020
Last Verified: September 2020

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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.: Yes
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Ustekinumab
Dermatologic Agents