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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 3

Conditions: Crohn Disease

Treatments: Drug: Ustekinumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03107793

2016-002918-43 (EudraCT Number)

CNTO1275CRD3005 (Other Identifier)

CR108276

Details and patient eligibility

About

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.

Full 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.

Enrollment: 500 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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500 participants in 4 patient groups

All Participants

Experimental group

Description:

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.

Treatment:

Drug: Ustekinumab

Routine Care Arm

Experimental group

Description:

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.

Treatment:

Drug: Ustekinumab

Treat to Target (T2T) Arm

Experimental group

Description:

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.

Treatment:

Drug: Ustekinumab

Exploratory Extension period: From Week 48 to Week 104

Experimental group

Description:

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.

Treatment:

Drug: Ustekinumab