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

Phase 1

• Conditions: Moderate to severe Ulcerative colitis or moderate to severe Crohn's disease; MedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 10017947 - Gastrointestinal disorders; MedDRA version: 20.0Level: LLTClassification code 10011400Term: Crohn's colitisSystem Organ Class: 10017947 - Gastrointestinal disorders; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2021-006881-19-AT
• Lead Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-12-14
• Last Update Posted: 22 April 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 240

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, anti-integrins, anti-IL-12/23 monoclonal antibodies, or anti-IL-23 mAbs, 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, anti-integrins, anti IL-12/23, or anti-IL-23 mAbs, JAK inhibitors, or S1P receptor .
-Intolerance: Discontinuation of anti-TNF, anti-integrins, 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, lymphopenia, and infections

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 non-passable 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. A 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 years or 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) >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 <35%) at screening.
l.Absolute neutrophil count <1.5x109/L or Hemoglobin <9 g/dL or
lymphocyte count <0.8x109/L or platelet count <100,000/mL
m.The patient has QTc>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 screening or 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 immunosuppressant

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified