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

NCT02749630 | Completed Phase 1 FDA Drug

• 2 other identifiers: GA294692015-002512-32
• Study Type: interventional
• Target: 70
• Locations: 2 countries
• Sites: 2

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants with Adverse Events

  Up to Day 134

Secondary Outcomes (7)

• Maximum Serum Concentration (Cmax) of UTTR1147A After the First and Last Dose

  Up to Day 134

• Minimum (Trough) Serum Concentrations (Ctrough) of UTTR1147A Prior to the Second and Last Dose

  Up to Day 134

• Total Serum Clearance (CL) of UTTR1147A

  Up to Day 134

• Volume of Distribution (V) of UTTR1147A

  Up to Day 134

• Area Under the Concentration vs. Time Curve (AUC) Within a Dose Interval (AUCtau) After the Final Dose of UTTR1147A

  Up to Day 134

Study Arms (3)

Healthy Volunteer

EXPERIMENTAL

Participants will be given escalating doses of UTTR1147A or Placebo intravenously

Drug: Placebo; Drug: UTTR1147A

Ulcerative Colitis

EXPERIMENTAL

Participants will be given escalating doses of UTTR1147A or Placebo intravenously

Drug: Placebo; Drug: UTTR1147A

Crohn's Disease

EXPERIMENTAL

Participants will be given escalating doses of UTTR1147A or Placebo intravenously

Drug: Placebo; Drug: UTTR1147A

Interventions

Placebo DRUG

Matching placebo to UTTR1147A administered intravenously

Crohn's Disease; Healthy Volunteer; Ulcerative Colitis

UTTR1147A DRUG

Escalating doses of intravenously administered UTTR1147A

Also known as: efmarodocokin alfa, RO7021610, RG7880, IL-22Fc

Crohn's Disease; Healthy Volunteer; Ulcerative Colitis

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (2)

Charité Research Organisation GmbH

Berlin, 10117, Germany

Location

Royal Victoria Infirmary

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 36732049 DERIVED

• 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.

  PMID: 31792136 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative; Crohn Disease

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2016
• First Posted: April 25, 2016
• Study Start: April 11, 2016
• Primary Completion: February 19, 2020
• Study Completion: February 19, 2020
• Last Updated: October 30, 2020

Record last verified: 2020-10

Locations

DE (1); GB (1)