A Safety Study of Intravenously Administered UTTR1147A in Healthy Volunteers (HVs), Participants With Ulcerative Colitis (UC), and Participants With Crohn's Disease (CD)

NCT ID: NCT02749630

Last Updated: 2020-10-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-11
• Study Completion Date: 2020-02-19

Brief Summary

This is a randomized, observer-blinded, placebo-controlled study to evaluate safety, tolerability, immunogenicity, and pharmacokinetics of repeat dosing of intravenous (IV) UTTR1147A. The study will consist of a repeat dose escalation in HVs, in participants with UC, and in participants with CD across multiple sites.

Conditions

Ulcerative Colitis; Crohn's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Healthy Volunteer

Participants will be given escalating doses of UTTR1147A or Placebo intravenously

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Matching placebo to UTTR1147A administered intravenously

UTTR1147A

Intervention Type: DRUG

Escalating doses of intravenously administered UTTR1147A

Ulcerative Colitis

Participants will be given escalating doses of UTTR1147A or Placebo intravenously

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Matching placebo to UTTR1147A administered intravenously

UTTR1147A

Intervention Type: DRUG

Escalating doses of intravenously administered UTTR1147A

Crohn's Disease

Participants will be given escalating doses of UTTR1147A or Placebo intravenously

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Matching placebo to UTTR1147A administered intravenously

UTTR1147A

Intervention Type: DRUG

Escalating doses of intravenously administered UTTR1147A

Interventions

Placebo

Matching placebo to UTTR1147A administered intravenously

Intervention Type: DRUG

UTTR1147A

Escalating doses of intravenously administered UTTR1147A

Intervention Type: DRUG

Other Intervention Names

efmarodocokin alfa; RO7021610; RG7880; IL-22Fc

Eligibility Criteria

Inclusion Criteria

• No history of malignancy
• Documentation of age-appropriate cancer screening based on local/country-specific guidelines
• For women of childbearing potential: agreement to remain abstinent or use contraceptive methods
• For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm

For HVs Only:

• Age 18 - 50
• Body mass index (BMI) between 18 and 32 kilograms per square meter (kg/m2), inclusive
• In good health, determined by no clinically significant findings from medical history, 12-lead electrocardiogram (ECG), and vital signs, and clinical laboratory evaluations should be within the reference range for the test laboratory unless deemed not clinically significant by the investigator and Sponsor

For Participants with UC or CD:

• Age 18 - 80
• Eligible to receive biologic therapy
• Disease duration of >/= 12 weeks
• Diagnosis of moderate to severe UC or CD

Exclusion Criteria

• History of inflammatory skin disorders
• History of any cancer
• History of anaphylaxis, hypersensitivity, or drug allergies
• History of alcoholism or drug addiction
• Positive tests indicating infection for hepatitis C, hepatitis B, or HIV
• Use of a non-biologic investigational drug or participation in an investigational study with a non-biologic drug within 30 days or 5 half-lives of investigational product, whichever is greater, prior to study drug administration
• Use of a biologic investigational therapy or participation in an investigational study involving biologic therapy within 90 days or 5 half-lives, whichever is greater, prior to study drug administration
• History or presence of an abnormal ECG that is clinically significant in the investigator's opinion
• Family history of sudden unexplained death or long QT syndrome
• Any acute or chronic condition that would limit the subject's ability to complete and/or participate in this clinical study
• Pregnant or lactating, or intending to become pregnant for duration of study

For HVs Only:

• Known family history of gastrointestinal (GI) and/or colon cancer
• Prior exposure to UTTR1147A

For Participants with UC or CD:

• Significant uncontrolled co-morbidity, such as neurological, cardiac, pulmonary, renal, hepatic, endocrine, or GI disorders
• History of primary sclerosing cholangitis
• Active anti-TNF induced psoriasiform or eczematous lesions
• Moderate to severe anemia
• Presence of an ileostomy or colostomy
• Total proctocolectomy
• Positive screening for latent mycobacterial tuberculosis infection
• Impaired renal function
• Impared hepatic function

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Charité Research Organisation GmbH

Berlin, , Germany

Royal Victoria Infirmary

Newcastle upon Tyne, , United Kingdom

Countries

Germany; United Kingdom

References

Wagner F, Mansfield JC, Lekkerkerker AN, Wang Y, Keir M, Dash A, Butcher B, Harder B, Orozco LD, Mar JS, Chen H, Rothenberg ME. Dose escalation randomised study of efmarodocokin alfa in healthy volunteers and patients with ulcerative colitis. Gut. 2023 Aug;72(8):1451-1461. doi: 10.1136/gutjnl-2022-328387. Epub 2023 Feb 2.

Reference Type: DERIVED

PMID: 36732049 (View on PubMed)

Powell N, Pantazi E, Pavlidis P, Tsakmaki A, Li K, Yang F, Parker A, Pin C, Cozzetto D, Minns D, Stolarczyk E, Saveljeva S, Mohamed R, Lavender P, Afzali B, Digby-Bell J, Tjir-Li T, Kaser A, Friedman J, MacDonald TT, Bewick GA, Lord GM. Interleukin-22 orchestrates a pathological endoplasmic reticulum stress response transcriptional programme in colonic epithelial cells. Gut. 2020 Mar;69(3):578-590. doi: 10.1136/gutjnl-2019-318483. Epub 2019 Dec 2.

Reference Type: DERIVED

PMID: 31792136 (View on PubMed)

Other Identifiers

2015-002512-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GA29469

Identifier Type: -

Identifier Source: org_study_id