A Study to Test the 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 is to characterize the efficacy TEV-48574 in adult participants with IBD (moderate to severe Ulcerative Colitis (UC) or Crohn's Disease (CD)) as assessed by induction of clinical remission (UC) and endoscopic response (CD) at week 14. Secondary objectives: To evaluate the efficacy and dose response of the 2 different dose regimens as assessed by multiple standard measures To evaluate the safety and tolerability of the 2 different dose regimens To evaluate the immunogenicity of the 2 different dose regimens The study will consist of a screening period of up to 6 weeks (42 days), a 14-week treatment period, and a 4-week follow-up period.

Official Title
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A 14 Week Phase 2b, Randomized, Double-Blind, Dose-Ranging Study to Determine the Pharmacokinetics, Efficacy, Safety and Tolerability of TEV-48574 in Adult Patients With Ulcerative Colitis or Crohn's Disease (RELIEVE UCCD)

Conditions
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Crohn Disease, Colitis, Ulcerative

Intervention / Treatment
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* Drug: TEV-48574
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Ulcerative Colitis (UC) or Crohn's Disease (CD) for ≥3 months The participant is able to communicate satisfactorily with the investigator and to participate in, and comply with, the requirements of the study The participant is able to understand the nature of the study and any potential hazards associated with participating in the study Women of non-childbearing potential who are either surgically (documented hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or congenitally sterile as assessed by a physician, or 1-year postmenopausal Male participants (including vasectomized) with women of childbearing potential (WOCBP) partners (whether pregnant or not) must use condoms after the first investigational medicinal product (IMP) administration and throughout the study or until 50 days after the last IMP dose, whichever is longer NOTE- Additional criteria apply, please contact the investigator for more information Exclusion Criteria: The 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 Diagnosis of indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic coliti Participant has colonic dysplasia or neoplasia, toxic megacolon, primary sclerosing cholangitis, known non-passable colonic stricture, presence of colonic or small bowel stoma, presence of non-passable colonic or small bowel obstruction or resection preventing the endoscopy procedure, or fulminant colitis Presence of active enteric infections (positive stool culture) or a history of serious infection (requiring parenteral antibiotic and/or hospitalization) within 4 weeks prior to the first screening visit Participant anticipates requiring major surgery during this study. A participant is Hepatitis B core antibody or surface antigen positive and/or Hepatitis C antibody positive with detectable ribonucleic acids, or positive human immunodeficiency virus types 1 or 2 at screening. A history of an opportunistic infection (eg, cytomegalovirus retinitis, Pneumocystis carinii, or aspergillosis) A history of more than 2 herpes zoster episode in the last 5 years or multimetameric herpes zoster A history of or ongoing chronic or recurrent serious infectious disease (eg, infected indwelling prosthesis or osteomyelitis) The 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. Presence of a transplanted organ A history of malignancy within the last 5 years (exception: basal cell carcinoma or in situ carcinoma of the cervix if successful curative therapy occurred at least 12 months prior to screening) or curatively resected papillary thyroid cance Current or history (within 2 years) of serious psychiatric disease or alcohol or drug abuse Participants with incurable diseases, persons in nursing homes, and participants incapable of giving written informed consent 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 A (UC)<br>Dose regimen A administered by subcutaneous infusion for participants with UC | Drug: TEV-48574<br>* Subcutaneous infusion<br>|
| Experimental: TEV-48574 Dose B (UC)<br>Dose regimen B administered by Subcutaneous infusion for participants with UC | Drug: TEV-48574<br>* Subcutaneous infusion<br>|
| Experimental: TEV-48574 Dose A (CD)<br>Dose regimen A administered by subcutaneous infusion for participants with CD | Drug: TEV-48574<br>* Subcutaneous infusion<br>|
| Experimental: TEV-48574 Dose B (CD)<br>Dose regimen B administered by subcutaneous infusion for participants with CD | Drug: TEV-48574<br>* Subcutaneous infusion<br>|
| Placebo Comparator: Placebo UC<br>Matching Placebo | Drug: Placebo<br>* Matching Placebo<br>|
| Placebo Comparator: Placebo CD<br>Matching Placebo | Drug: Placebo<br>* Matching Placebo<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 UC who show clinical remission as defined by the Mayo score | Clinical remission is a 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 Each parameter of the score ranges from 0 (normal or inactive disease) to 3 (severe activity) and the total score from 0 to 9, respectively | Week 14 | 
| Number of participants with moderate to severe CD who show an endoscopic response as defined by the Endoscopic Score for Crohn's Disease | Endoscopic response defined as a reduction in Simple Endoscopic Score for Crohn's Disease (SES-CD) of at least 50% from baseline | Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with moderate to severe UC with a clinical response as defined by a decrease from baseline in Mayo score | Clinical response at week 14, 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 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 | Baseline and Week 14 | 
| 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 14 | 
| 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 14 | 
| Number of participants with moderate to severe UC with a clinical response as defined as a decrease from baseline in 2-item patient-reported outcome (PRO2) | Clinical response defined as decrease from baseline of at least 50% in 2-item patient-reported outcome (PRO2; rectal bleeding and stool frequency) | Baseline and Week 14 | 
| Number of participants with moderate to severe UC in Clinical remission as defined by PRO2 score | Clinical remission defined as score of rectal bleeding = 0 and stool frequency = 0 on the PRO2 scale | Week 14 | 
| Number of participants with moderate to severe CD with a clinical response with a decrease from baseline in Crohn's Disease Activity Index (CDAI) | Clinical response defined as a ≥100-point decrease in CDAI score | Baseline, Weeks 4, 8, 12 and 14 | 
| 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 14 | 
| Number of participants with moderate to severe CD with a clinical response as defined by PRO2 score | Clinical response defined as a decrease from baseline of at least 50% in PRO2 (PRO2 is defined as having 2 components, abdominal pain and stool frequency) | Baseline and Week 14 | 
| Number of participants with moderate to severe CD in clinical remission as defined by PRO2 score | Clinical remission defined as abdominal pain ≤1 and stool frequency ≤3 on the PRO2 scale | Week 14 | 
| Number of participants with moderate to severe CD with an Endoscopic response as defined by the Modified Multiplier-Simple Endoscopic Score (MM-SES-CD) | Endoscopic response defined as a decrease from baseline in Modified Multiplier-Simple Endoscopic Score (MM-SES-CD) of >50%. The MM-SES-CD takes into account the chances of each parameter (presence of ulcers, percentage of ulcerated surfaces, affected surface, and presence of strictures) achieving endoscopic remission. | Baseline and Week 14 | 
| 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. | Baseline up to Week 18 | 
| Number of participants who stopped taking the investigational medicinal product (IMP) due to adverse events |  | Up to Week 18 | 
| Number of Participants with Treatment Emergent Anti-Drug Antibodies (ADA) |  | Baseline, Weeks 2, 4, 8, 14, and 18 | 
| Number of ADA positive participants with the presence of neutralizing ADA |  | Weeks 2, 4, 8, 14, and 18 |