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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Ulcerative Colitis, Crohn's Disease

Intervention / Treatment
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* Drug: Placebo
* Drug: UTTR1147A


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Volunteer<br>Participants will be given escalating doses of UTTR1147A or Placebo intravenously | Drug: Placebo<br>* Matching placebo to UTTR1147A administered intravenously<br>Drug: UTTR1147A<br>* Escalating doses of intravenously administered UTTR1147A<br>* Other names: IL-22Fc;|
| Experimental: Ulcerative Colitis<br>Participants will be given escalating doses of UTTR1147A or Placebo intravenously | Drug: Placebo<br>* Matching placebo to UTTR1147A administered intravenously<br>Drug: UTTR1147A<br>* Escalating doses of intravenously administered UTTR1147A<br>* Other names: IL-22Fc;|
| Experimental: Crohn's Disease<br>Participants will be given escalating doses of UTTR1147A or Placebo intravenously | Drug: Placebo<br>* Matching placebo to UTTR1147A administered intravenously<br>Drug: UTTR1147A<br>* Escalating doses of intravenously administered UTTR1147A<br>* Other names: IL-22Fc;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |