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

Teva Branded Pharmaceutical Products R&D, Inc.290 enrolled

Overview

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 of 2 different doses of TEV-48574 as assessed by multiple standard measures * To evaluate the safety and tolerability of 2 different doses of TEV-48574 * To evaluate the immunogenicity of 2 different dioses of TEV-48574 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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

290

Conditions

Crohn Disease Colitis, Ulcerative

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (164)

Teva Investigational Site 15568

Sun City, Arizona, United States

Teva Investigational Site 15556

San Diego, California, United States

Teva Investigational Site 15747

San Diego, California, United States

Teva Investigational Site 15357

Kissimmee, Florida, United States

Teva Investigational Site 15563

Miami, Florida, United States

Outcomes

Primary Outcomes

Number of Participants With Moderate to Severe UC Who Showed Clinical Remission as Defined by the MMS

The MMS is a tool designed to measure disease activity for UC. It consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore as determined during central review. Each subscore was graded from 0 (normal) to 3 (severe). These individual subscores were summed up to give a total MMS ranging from 0 (normal or inactive disease) to 9 (severe disease), where higher scores indicated more severe disease activity. Clinical remission was defined as MMS ≤2 points with Mayo stool frequency subscore of 0 or 1, Mayo rectal bleeding subscore of 0, and centrally read endoscopic score of 0 or 1, where a score of 1 did not include "friability".

Time frame: Week 14

Number of Participants With Moderate to Severe CD Who Showed an Endoscopic Response as Defined by the SES-CD

The SES-CD assessed the degree of inflammation. The SES-CD assesses the following 4 components: presence of ulcers, percentage of ulcerated surfaces, affected surface, and presence of strictures. Each of these components was scored on a scale of 0 (none/unaffected) to 3 (worst). In the SES-CD, each of these 4 components was assessed in the 5 segments: the rectum, sigmoid and left colon, transverse colon, right colon, and ileum. The SES-CD was the sum of the individual scores of each of the components across the 5 segments. The range of SES-CD scores was 0 (none) - 12 (severe) for each segment, and 0 (none) - 60 (severe) for the overall SES-CD score, with larger scores indicating greater degree of inflammation. Endoscopic response at Week 14 in participants with moderate to severe CD was defined as a reduction in SES-CD of at least 50% from baseline.

Time frame: Baseline to Week 14

Secondary Outcomes

Number of Participants With Moderate to Severe UC With a Clinical Response as Defined by the MMS

The MMS is a tool designed to measure disease activity for UC. It consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore as determined during central review. Each subscore was graded from 0 (normal) to 3 (severe). These individual subscores were summed up to give a total MMS ranged from 0 (normal or inactive disease) to 9 (severe disease), where higher scores indicated more severe disease activity. Clinical response was defined as a decrease from baseline in the MMS 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 ≤1.

Time frame: Baseline to Week 14

Number of Participants With Moderate to Severe UC With Endoscopic Improvement as Defined by the Mayo Endoscopic Subscore (MES)

The endoscopic subscore evaluation for the MMS consisted of independent, blinded, central review of a high-resolution recorded video. The endoscopic subscore assessed disease activity from 0 (normal or inactive disease) to 3 (severe activity). Higher scores indicated more severe disease activity. Endoscopic improvement was defined as a MES of 0 or 1 at Week 14.

Time frame: Week 14

Number of Participants With Moderate to Severe UC With Endoscopic Remission as Defined by the MES

Time frame: Week 14

Number of Participants With Moderate to Severe UC With a Clinical Response as Defined by 2-item Patient-reported Outcome (PRO2) Score

The PRO2-UC score was derived from 2 parameters from the MMS: stool frequency and rectal bleeding, recorded daily by the participant using a handheld electronic diary over each of the preceding 7 days. Each parameter ranged from 0 (normal) to 3 (severe) with each subscore representing an average over the preceding 7 days. The total score was the summation of the subscores and therefore ranged from 0 (normal or inactive disease) to 6 (severe activity), where higher scores indicated more severe disease activity. Clinical response was defined as decrease from baseline of at least 50% in PRO2 (stool frequency and rectal bleeding) at Week 14.

Time frame: Baseline to Week 14

Number of Participants With Moderate to Severe UC With a Clinical Remission as Defined by PRO2 Score

The PRO2-UC score was derived from 2 parameters from the MMS: stool frequency and rectal bleeding, recorded daily by the participant using a handheld electronic diary over each of the preceding 7 days. Each parameter ranged from 0 (normal) to 3 (severe) with each subscore representing an average over the preceding 7 days. The total score was the summation of the subscores and therefore ranged from 0 (normal or inactive disease) to 6 (severe activity), where higher scores indicated more severe disease activity. Clinical remission was defined as score of stool frequency = 0 and rectal bleeding = 0 on the PRO2 scale at Week 14.

Time frame: 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)

The MM-SES-CD is an endoscopic scoring tool that considers each individual parameter's prognostic value for achieving endoscopic remission while on active therapy. The SES-CD assesses the following 4 components: presence of ulcers, percentage of ulcerated surfaces, affected surface, and presence of strictures. Each of these components was scored on a scale of 0 (none/unaffected) to 3 (worst). In the SES-CD, each of these 4 components was assessed in the 5 segments: the rectum, sigmoid and left colon, transverse colon, right colon, and ileum. The SES-CD was the sum of the individual scores of each of the components across the 5 segments. The range of SES-CD scores was 0 (none) - 12 (severe) for each segment, and 0 (none) - 60 (severe) for the overall SES-CD score, with higher scores indicating a greater degree of inflammation. Endoscopic response was defined as a decrease in MM-SES-CD of ≥50% from baseline at Week 14.

Time frame: Baseline to Week 14

Number of Participants With Moderate to Severe CD With a Clinical Response as Defined by Crohn's Disease Activity Index (CDAI) Score

The CDAI score consisted of an adjusted composite sum of 8 parameters, including daily diary evaluation for severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight, and hematocrit. The subscores of abdominal pain (0 \[no pain\] to 3 \[worst pain\]), general well-being (0 \[well\] to 4 \[terrible\]), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score that ranged from 0 (none) to 600 (severe) with a higher score indicating a worse outcome. Clinical response was defined as a ≥100-point decrease in CDAI score from baseline.

Time frame: Baseline to Weeks 4, 8, 12 and 14

Number of Participants With Moderate to Severe CD With a Clinical Remission as Defined by CDAI Score

The CDAI score consisted of an adjusted composite sum of 8 parameters, including daily diary evaluation for severity of abdominal pain, general well-being, very soft/liquid stool frequency, extra-intestinal symptoms, need for antidiarrheal drugs, presence of an abdominal mass, body weight, and hematocrit. The subscores of abdominal pain (0 \[no pain\] to 3 \[worst pain\]), general well-being (0 \[well\] to 4 \[terrible\]), and number of very soft or liquid stools were then summed over the 7 days prior to each visit. Additionally, the remaining predictors were also noted and weighted to create the total CDAI score that ranged from 0 (none) to 600 (severe) with a higher score indicating a worse outcome. Clinical remission was defined as a CDAI score \<150 at Week 14.

Time frame: Week 14

Number of Participants With Moderate to Severe CD With a Clinical Response as Defined by PRO2-CD Score

The PRO2-CD score was the sum of the daily stool frequency subscore (0 \[normal\] to 3 \[severe\]) and abdominal pain subscore (0 \[no pain\] to 3 \[worst pain\]) from the CDAI. Total PRO2-CD score ranged from 0 (normal) - 6 (severe), with higher scores indicating more severe disease. These were recorded daily by the participant using a handheld electronic diary over each of the preceding 7 days. Clinical response was defined as a decrease from baseline of at least 50% in PRO2-CD (abdominal pain and stool frequency) at Week 14.

Time frame: Baseline to Week 14

Number of Participants With Moderate to Severe CD With a Clinical Remission as Defined by PRO2-CD Score

The PRO2-CD score was the sum of the daily stool frequency subscore (0 \[normal\] to 3 \[severe\]) and abdominal pain subscore (0 \[no pain\] to 3 \[worst pain\]) from the CDAI. Total PRO2-CD score ranged from 0 (normal) - 6 (severe), with higher scores indicating more severe disease. These were recorded daily by the participant using a handheld electronic diary over each of the preceding 7 days. Clinical remission was defined as abdominal pain ≤1 and stool frequency ≤3 on the PRO2-CD scale at Week 14

Time frame: Week 14

Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)

An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs were considered TEAEs if onset occurred on or after the first dose date. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Time frame: Baseline (Day 1) up to Week 18

Number of Participants Who Stopped Taking the Investigational Medicinal Product (IMP) Due to AEs

An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Time frame: Baseline (Day 1) up to Week 18

Number of Participants With Treatment-emergent Anti-Drug Antibodies (ADAs)

Treatment-emergent ADA positive: - the participant had a positive ADA sample (after first dose of study drug) but not at baseline (prior to first dose of study drug), or - the participant had a positive ADA sample at baseline (prior to first dose of study drug) and at the visit (after first dose of study drug), with at least a 4-fold increase in titer level.

Time frame: Weeks 2, 4, 8, 14, and 18

Number of ADA Positive Participants With the Presence of Neutralizing ADA

Time frame: Weeks 2, 4, 8, 14, and 18