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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Teva Branded Pharmaceutical Products R&D Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

17 Mar 2023 → 13 Nov 2024

Decision date (initial)

2024-05-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Teva Branded Pharmaceutical Products R&D, Inc.

External identifiers

EU CT number

2024-511089-36-00

EudraCT number

2021-006881-19

ClinicalTrials.gov

NCT05499130

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Dose response, Efficacy

The primary objective of the study is to characterize the efficacy of TEV-48574 sc administered every 2 weeks (Q2W) in adult patients with IBD (moderate to severe UC or CD), as assessed by induction of clinical remission (UC) and endoscopic response (CD) at week 14.

Secondary objectives 3

1. 1. A secondary objective of the study is 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.
2. 2. A secondary objective of the study is to evaluate the safety and tolerability of 2 different doses of TEV-48574 sc administered Q2W in adult patients with IBD (moderate to severe UC or CD).
3. 3. A secondary objective of the study is to evaluate the immunogenicity of 2 different doses of TEV 48574 sc administered Q2W in adult patients with IBD (moderate to severe UC or CD).

Conditions and MedDRA coding

Crohn’s disease

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1.Adults of male and female sex (without restrictions on gender) between 18 and 75 years of age, inclusive, at the time of informed consent.
2. 2.The patient is able to communicate satisfactorily with the investigator and to participate in, and comply with, the requirements of the study.
3. 3.The patient is able to understand the nature of the study and any potential hazards associated with participating in the study
4. 4.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
5. 5. Male patients (including vasectomized) with WOCBP partners (whether pregnant or not) must use condoms after the first IMP administration and throughout the study or until 50 days after the last IMP dose, whichever is longer

Exclusion criteria 14

1. 1.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.
2. 2.Diagnosis of indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis.
3. 3. 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.
4. 4. 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.
5. 5.Patient anticipates requiring major surgery during this study.
6. 6. Hepatitis B core antibody (HBcAb) or surface antigen (HBsAg) positive. If HBcAb is positive and 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. Positive human immunodeficiency virus types 1 or 2 at screening.
7. 7.A history of an opportunistic infection (eg, cytomegalovirus retinitis, Pneumocystis carinii, or aspergillosis).
8. 8.A history of more than 2 herpes zoster episodes in the last 5 years or multimetameric herpes zoster
9. 9.A history of or ongoing chronic or recurrent serious infectious disease (eg, infected indwelling prosthesis or osteomyelitis).
10. 10.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.
11. 11.Presence of a transplanted organ.
12. 12.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).
13. 13.Current or history (within 2 years) of serious psychiatric disease or alcohol or drug abuse.
14. 14.Patients with incurable diseases, persons in nursing homes, and patients incapable of giving written informed consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1.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”.
2. 2. Endoscopic response defined as a reduction in Simple Endoscopic Score for Crohn’s Disease (SES CD) of at least 50% from baseline.

Secondary endpoints 8

1. 1.In patients with moderate to severe UC: 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.
2. 2. In patients with moderate to severe UC: 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.
3. 3.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 <150 at week 14.
4. 4.In patients with moderate to severe CD are as follows:-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) at week 14.
5. 5.In patients with moderate to severe CD are as follows: Clinical remission defined as abdominal pain ≤1 and stool frequency ≤3 on the PRO2 scale at week 14. Endoscopic response defined as a decrease in modified multiplier (MM)-SES-CD of >50% from baseline at week 14.
6. 6. Safety and tolerability measures/parameters: Adverse events; Change from baseline in clinical laboratory test results (serum chemistry, hematology, and urinalysis).
7. 7. Safety and tolerability measures/parameters: 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.
8. 8.Immunogenicity endpoints:-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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Teva Branded Pharmaceutical Products R&D Inc.

Sponsor organisation

Teva Branded Pharmaceutical Products R&D Inc.

Address

145 Brandywine Parkway

City

West Chester

Postcode

19380-4245

Country

United States

Scientific contact point

Organisation

Teva Branded Pharmaceutical Products R&D Inc.

Contact name

Medical Information

Public contact point

Organisation

Teva Branded Pharmaceutical Products R&D Inc.

Contact name

Medical Information

Third parties 14

Locations

12 EU/EEA countries · 53 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 98 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications