Moderate to severe Ulcerative colitis or moderate to severe Crohn's disease MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 10017947 - Gastrointestinal disorders MedDRA version: 20.0 Level: LLT Classification code 10011400 Term: Crohn's colitis System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Product Name: TEV-48574
Product Code: TEV-48574
Pharmaceutical Form: Solution for injection
INN or Proposed INN: TEV-48574
CAS Number: 2750005-84-4
Current Sponsor code: TEV-48574
Other descriptive na
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a.Adults of male and female sex (without restrictions on gender) between 18 and 75 years of age, inclusive, at the time of informed consent. b.Diagnosis of UC or CD for =3 months. c.UC pts: Patient with moderate to severe active UC as defined by the 3 component modified Mayo score of 5 to 9, inclusive, with an endoscopic subscore of =2 (from central reading) d.CD pts: Patient with moderate to severe active CD as determined by a CDAI score of =220 and =450. e.CD pts: SES CD score of =6 (=4 for isolated ileal disease). f.UC pts: Active disease beyond the rectum (>15 cm of active disease at the screening endoscopy [sigmoidoscopy]). g.Patient must have inadequate response to, loss of response to, or intolerance -At least 1 of the following therapies: corticosteroids, immunosuppressants, or an approved advanced therapy for IBD including biologics (anti-TNF, anti-integrins, anti IL 12/23, or anti-IL- 23), JAK inhibitors, or S1P receptor modulators. No more than 3 locally approved classes of biologics. •Inadequate response to, loss of response to, or intolerance to corticosteroid treatment is defined as 1 or more of the following: -Steroid refractory: persistent symptoms of active disease despite treatment with at least one 4-week induction regimen that included a dose of =30 mg prednisone (oral) daily for at least 2 weeks or intravenous (iv) for at least 1 week within the previous 5 years; -Steroid dependent: 2 failed attempts to taper steroids below a dose equivalent to 10 mg prednisone (oral) daily within the previous year; -Steroid intolerant: history of intolerance to corticosteroids (including, but not limited to, Cushing's syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, and infection) within the previous 5 years. •Inadequate response to, loss of response to, or intolerance to prior immunosuppressant treatment is defined by 1 or more of the following: -Persistent signs and symptoms of active disease despite a history of at least 1 regimen of oral azathioprine (AZA) or 6 mercaptopurine (6-MP) and/or methotrexate consistent with the regional standard of care; -History of intolerance to AZA, 6-MP, or methotrexate (including, but not limited to, nausea/vomiting, abdominal pain, pancreatitis, liver function testing abnormalities, lymphopenia, thiopurine methyltransferase genetic mutation, and infection). •Inadequate response to, loss of response to, or intolerance to prior advanced therapy for IBD (biologics, JAK inhibitors, and S1P receptor modulators) defined as 1 or more of the following: -Loss of response: Persistent signs and symptoms of active disease despite at least one induction and one maintenance regimen of the locally approved regimen of anti-TNF inhibitors, anti-integrins, anti-IL-12/23 monoclonal antibodies, JAK inhibitors, or S1Preceptor modulators. -Inadequate response (primary non-response): Persistent signs and symptoms of active disease despite at least one induction regimen of the locally approved highest dosing regimen of anti-TNF inhibitors, anti-integrins, anti-IL-12/23 or anti-IL-23 mAbs, JAK inhibitors, or S1P receptor modulators. -Intolerance: Discontinuation of anti-TNF inhibitors, anti-integrins, anti-IL-12/23 anti-IL-12/23 or anti IL-23 Mabs, JAK inhibitors, or S1P receptor modulators due to an adverse drug reaction as determined by treating physician. Such adverse drug reactions include, but are not limited to, nausea/vomiting, abdominal pain, pancreatitis, liver function testing abnormalities, l
Exclusion criteria
Exclusion criteria: a.The patient has any concomitant conditions or treatments that could interfere with study conduct, influence the interpretation of study observations/results, or put the patient at increased risk during the study as judged by the investigator and/or the clinical study physician. b.Diagnosis of indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis. c.Patient has colonic dysplasia or neoplasia,(with exception of dysplasia on a completely excised adenomatous polyp [not a sessile one]), toxic megacolon, primary sclerosing cholangitis, known non-passable colonic stricture, presence of colonic or small bowel stoma, presence of nonpassable colonic or small bowel obstruction or resection preventing the endoscopy procedure, or fulminant colitis. d.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. e.Patient anticipates requiring major surgery during this study. f.patient is Hepatitis B (HBcAb) core antibody or surface antigen (HBsAg) positive. If HBcAb is positive and/or HBsAg negative, Hepatitis B viral deoxyribonucleic acid (DNA) will be done as reflective test, and, if undetectable, then not exclusionary. Hepatitis C antibody positive with detectable RNAs, or positive human immunodeficiency virus types 1 or 2 at screening. g.Tested positive for tuberculosis (TB) at screening by the QuantiFERON® TB Gold Test(unless documentation of prior TB treatment is available) or had a history of untreated latent or active TB. h.A history of an opportunistic infection (eg, cytomegalovirus retinitis, Pneumocystis carinii, or aspergillosis). i.A history of more than 2 herpes zoster episodes in the last 5 yearsor multimetameric herpes zoster. j.A history of or ongoing chronic or recurrent serious infectious disease (eg, infected indwelling prosthesis or osteomyelitis). k.Current or history of chronic liver or biliary disease (with the exception of Gilbert’s syndrome, asymptomatic gallstones or uncomplicated fatty liver disease) at screening or baseline alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2x upper limit of normal (ULN) or bilirubin >1.5x ULN (isolated bilirubin >1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin 480 ms n.Any acute infection which in the opinion of the investigator compromises the safety of the patient. o.The patient 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. p.The patient has a known hypersensitivity to the IMP and/or excipients. q.Presence of a transplanted organ. r.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 screeningor curatively resected papillary thyroid cancer). s.Patient is receiving any of the following therapies within the designated time period: -The patient is currently using any systemic
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to characterize the efficacy of TEV-48574 sc administered every two weeks (Q2W) and to evaluate the efficacy in adult patients with Inflammatory Bowel disease (IBD) (IBD with moderate to severe UC or CD), as assessed by induction of clinical remission (UC) and endoscopic response (CD) at week 14.;Secondary Objective: To evaluate the efficacy of 2 different doses of TEV-48574 sc administered Q2W in adult patients with IBD (moderate to severe UC or CD) as assessed by multiple standard measures at week 14. Other: - to evaluate the safety and tolerability of 2 doses of TEV-48574 - to evaluate the immunogenicity of 2 different doses Exploratory objectives include: - to evaluate the efficacy of 2 different doses - to evaluate the safety and tolerability of 2 different doses - evaluate association among exploratory biomarkers and clinical efficacy of TEV 48574 - to obtain trough serum TEV 48574 concentrations, to compare major pharmacokinetic (PK) characteristics between UC and CD patients with healthy volunteers and asthma patients, and, if data allows, to evaluate the pharmacokinetics/PD and/or exposure-response relationship of different doses of TEV-48574 sc - to evaluate the effect of genetic polymorphisms on clinical efficacy in adult patients with IBD (moderate to severe UC or CD);Primary end point(s): The primary efficacy endpoint is response (yes or no) at week 14, where response in UC patients is defined as clinical remission and response in CD patients is defined as endoscopic response. Clinical remission and endoscopic response are determined as follows: • Clinical remission at week 14 in patients with moderate to severe UC. 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 “f | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints to be measured in patients with moderate to severe UC are as follows: • 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 • Endoscopic improvement defined as a Mayo endoscopic subscore of 0 or 1 at week 14 • Endoscopic remission defined as a Mayo endoscopic subscore of 0 at week 14 • Clinical response defined as decrease from baseline of at least 50% in 2-item patient-reported outcome (PRO2; rectal bleeding and stool frequency) at week 14 • Clinical remission defined as score of rectal bleeding = 0 and stool frequency = 0 on the PRO2 scale at week 14 The secondary efficacy endpoints to be measured in patients with moderate to severe CD are as follows: • Clinical response defined as a =100-point decrease in Crohn's Disease Activity Index (CDAI) score from baseline at weeks 4, 8, 12 and 14 • Clinical remission defined as a CDAI score 50% from baseline at week 14 Other secondary endpoints include: Safety and tolerability measures/parameters as follows: • Adverse events • Change from baseline in clinical laboratory test results (serum chemistry, hematology, and urinalysis) • Change from baseline in vital signs measurements (blood pressure, pulse rate, body temperature, and respiratory rate) • Change from baseline in 12-lead electrocardiogram (ECG) findings • Patients who stopped the IMP due to adverse events • Local tolerability at the injection site Immunogenicity endpoints as follows: • Change from baseline in treatment-emergent anti-drug antibody (ADA) at weeks 2, 4, 8, 14, and follow-up visit • Presence of neutralizing ADA in ADA positive patients at weeks 2, 4, 8, 14, and follow-up visit Exploratory endpoints include | — |
Countries
Austria, Belgium, Bulgaria, Canada, Czechia, Czech Republic, France, Georgia, Germany, Hungary, Israel, Italy, Japan, Moldova, Republic of, Norway, Poland, Serbia, Slovakia, South Africa, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Study Lead
Teva Branded Pharmaceutical Products R&D, Inc.
Outcome results
None listed