A Study to Evaluate the Long-Term Effect of TEV-48574 in Moderate to Severe Ulcerative Colitis or Crohn's Disease

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the efficacy and dose response of 2 different maintenance dose regimens of TEV-48574 subcutaneous (sc) administered every 4 weeks (Q4W) in adult participants with inflammatory bowel disease (IBD). Secondary objectives of the study are to: evaluate the efficacy of 2 different maintenance dose regimens of TEV-48574 sc administered Q4W in adult participants with IBD evaluate the safety and tolerability of 2 different maintenance dose regimens of TEV-48574 sc administered Q4W in adult participants with IBD evaluate the immunogenicity of 2 different maintenance dose regimens of TEV-48574 sc administered Q4W in adult participants with IBD The total duration of participant participation in the study is planned to be up to 66 weeks for each individual participant. The study duration is approximately 37 months.

Official Title
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A 44-Week Phase 2b Long-Term Extension, RandomizEd, Double-BLind, Study to Determine the Long-Term PharmacokInetics, Efficacy, Safety, and Tolerability of TEV-48574 in Adult PatiEnts With Moderate to Severe Ulcerative Colitis or Crohn's Disease Who Completed the Main Phase of the Dose-Ranging Study (RELIEVE UCCD LTE)

Conditions
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Crohn Disease, Colitis, Ulcerative

Intervention / Treatment
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* Drug: TEV-48574 Dose Regimen A
* Drug: TEV-48574 Dose Regiment B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Maintenance Period- Participants who achieved clinical response and/or clinical remission at week 14 of TV48574-IMM-20036 (the 14-week DRF study) or in the re-induction period of this study. Re-induction- Participants who did not achieve clinical response and/or clinical remission at week 14 of the TV48574-IMM-20036 DRF study NOTE- Additional criteria may apply, please contact the investigator for more information Exclusion Criteria: Participants who discontinued the TV48574-IMM-20036 study before scheduled week 14 visit (any reason including lack of efficacy, safety, or personal reasons) Participant has any concomitant conditions or treatments that could interfere with study conduct, influence the interpretation of study observations/results, or put the participant at increased risk during the study as judged by the investigator and/or the clinical study physician. Participant anticipates requiring major surgery during this study. Participant is currently pregnant or lactating or is planning to become pregnant or to lactate during the study or for at least 50 days after administration of the last dose of IMP in case of early termination. Any woman becoming pregnant during the study will be withdrawn from the study. NOTE- Additional criteria apply, please contact the investigator for more information

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TEV-48574 Dose Regimen A for Ulcerative Colitis (UC)<br>Administered by subcutaneous infusion for participants with UC | Drug: TEV-48574 Dose Regimen A<br>* Subcutaneous (sc) administration using a commercial sc infusion system<br>|
| Experimental: TEV-48574 Dose Regimen A for Crohn's Disease (CD)<br>Administered by subcutaneous infusion for participants with CD | Drug: TEV-48574 Dose Regimen A<br>* Subcutaneous (sc) administration using a commercial sc infusion system<br>|
| Experimental: TEV-48574 Dose Regimen B for Ulcerative Colitis (UC)<br>Administered by subcutaneous infusion for participants with UC | Drug: TEV-48574 Dose Regiment B<br>* Subcutaneous (sc) administration using a commercial sc infusion system<br>|
| Experimental: TEV-48574 Dose Regimen B for Crohn's Disease (CD)<br>Administered by subcutaneous infusion for participants with CD | Drug: TEV-48574 Dose Regiment B<br>* Subcutaneous (sc) administration using a commercial sc infusion system<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with moderate to severe ulcerative colitis (UC) who show clinical remission as defined by the Mayo score | Clinical remission based on modified (9-point rectal bleeding, stool frequency, and endoscopy) Mayo score of ≤2 points, which is defined by: stool frequency subscore of 0 or 1, rectal bleeding subscore of 0, and endoscopic subscore of 0 or 1, where a score of 1 does not include friability | Week 44 | 
| Number of participants with moderate to severe Crohn's disease (CD) who show an endoscopic response as defined by the Endoscopic Score for Crohn's Disease | Endoscopic response, defined as a decrease in Simple Endoscopic Score for Crohn's Disease (SES-CD) of at least 50% from DRF study baseline at week 44 in participants with CD | Week 44 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with moderate to severe UC with a clinical response as defined by Mayo score | Clinical response at week 44, defined as a decrease from baseline in the modified (9-point rectal bleeding, stool frequency, and endoscopy) Mayo score of at least 2 points AND at least a 30% reduction from DRF baseline with either a decrease in rectal bleeding subscore of at least 1 or an absolute rectal bleeding subscore of less than or equal to 1 | Week 44 | 
| Number of participants with moderate to severe UC with Endoscopic improvement as defined by Mayo score | Endoscopic improvement defined as a Mayo endoscopic subscore of 0 or 1 | Week 44 | 
| Number of participants with moderate to severe UC in Endoscopic remission as defined by Mayo score | Endoscopic remission defined as a Mayo endoscopic subscore of 0 | Week 44 | 
| Number of participants with moderate to severe UC with Corticosteroid-free clinical remission based on the modified Mayo score | Defined by clinical remission and corticosteroid-free for ≥12 weeks preceding week 44 | Week 44 | 
| Number of participants with moderate to severe CD with a clinical response based on Crohn's Disease Activity Index | Clinical response defined as a ≥100-point decrease from DRF baseline Crohn's Disease Activity Index (CDAI) score | Week 44 | 
| Number of participants with moderate to severe CD in clinical remission as defined by CDAI score | Clinical remission defined as a CDAI score less than 150 | Week 44 | 
| Number of participants with moderate to severe CD with Corticosteroid-free endoscopic response based on SES-CD | Defined by endoscopic response and corticosteroid-free for ≥12 weeks preceding week 44 | Week 44 | 
| Number of participants with moderate to severe CD with Corticosteroid-free clinical remission based on CDAI | Defined by a CDAI score of <150 points and corticosteroid-free for ≥12 weeks preceding week 44 | Week 44 | 
| Number of Participants Who Experience Adverse Events | Adverse events include clinically significant changes in clinical laboratory test results (serum chemistry, hematology, and urinalysis), vital signs measurements (blood pressure, pulse rate, body temperature, and respiratory rate), 12-lead electrocardiogram (ECG), and injection site reactions. | Up to Week 48 | 
| Number of participants who stopped taking the investigational medicinal product (IMP) due to adverse events |  | Up to Week 48 | 
| Number of Participants with Treatment Emergent Anti-Drug Antibodies (ADA) |  | Weeks 0, 4, 8, 16, 28, 44, and 48 | 
| Number of ADA positive participants with the presence of neutralizing ADA |  | Weeks 0, 4, 8, 16, 28, 44, and 48 |