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

An Observer-Blinded, Placebo-Controlled, Multiple-Ascending, Dose-Escalation Study to Explore the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Repeat Intravenous Administrations of UTTR1147A in Healthy Volunteers and Patients With Ulcerative Colitis and Crohn's Disease

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.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease; Ulcerative Colitis
• Intervention / Treatment: Drug: Placebo; Drug: UTTR1147A

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charite Research Organisation GmbH
• United Kingdom
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

General 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:

General 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Volunteer; Participants will be given escalating doses of UTTR1147A or Placebo intravenously	Drug: Placebo; Matching placebo to UTTR1147A administered intravenously; Drug: UTTR1147A; Escalating doses of intravenously administered UTTR1147A; Other Names: RG7880; RO7021610; IL-22Fc; efmarodocokin alfa
Experimental: Ulcerative Colitis; Participants will be given escalating doses of UTTR1147A or Placebo intravenously	Drug: Placebo; Matching placebo to UTTR1147A administered intravenously; Drug: UTTR1147A; Escalating doses of intravenously administered UTTR1147A; Other Names: RG7880; RO7021610; IL-22Fc; efmarodocokin alfa
Experimental: Crohn's Disease; Participants will be given escalating doses of UTTR1147A or Placebo intravenously	Drug: Placebo; Matching placebo to UTTR1147A administered intravenously; Drug: UTTR1147A; Escalating doses of intravenously administered UTTR1147A; Other Names: RG7880; RO7021610; IL-22Fc; efmarodocokin alfa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with Adverse Events	Up to Day 134

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Elimination Half-Life (t1/2) of UTTR1147A	Up to Day 134
Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) in Serum	Up to Day 134

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2016
• Primary Completion (Actual): February 19, 2020
• Study Completion (Actual): February 19, 2020

Study Registration Dates

• First Submitted: April 12, 2016
• First Submitted That Met QC Criteria: April 20, 2016
• First Posted (Estimate): April 25, 2016

Study Record Updates

• Last Update Posted (Actual): October 30, 2020
• Last Update Submitted That Met QC Criteria: October 28, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Crohn Disease; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: GA29469; 2015-002512-32 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes