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

Phase 1

Completed

• Conditions: Ulcerative Colitis; Crohn's Disease
• Interventions: Drug: Placebo; Drug: UTTR1147A

• Registration Number: NCT02749630
• Lead Sponsor: Genentech, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-04-11
• Study First Submitted: 2016-04-12
• Study First Submitted QC: 2016-04-20
• Study First Posted: 2016-04-25
• Primary Completion: 2020-02-19
• Study Completion: 2020-02-19
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-28
• Last Update Posted: 2020-10-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ulcerative Colitis	Placebo	Participants will be given escalating doses of UTTR1147A or Placebo intravenously
Crohn's Disease	UTTR1147A	Participants will be given escalating doses of UTTR1147A or Placebo intravenously
Ulcerative Colitis	UTTR1147A	Participants will be given escalating doses of UTTR1147A or Placebo intravenously
Crohn's Disease	Placebo	Participants will be given escalating doses of UTTR1147A or Placebo intravenously
Healthy Volunteer	UTTR1147A	Participants will be given escalating doses of UTTR1147A or Placebo intravenously
Healthy Volunteer	Placebo	Participants will be given escalating doses of UTTR1147A or Placebo intravenously

Primary Outcome Measures

Name	Time	Method
Percentage of Participants with Adverse Events	Up to Day 134

Secondary Outcome Measures

Name	Time	Method
Minimum (Trough) Serum Concentrations (Ctrough) of UTTR1147A Prior to the Second and Last Dose	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
Total Serum Clearance (CL) of UTTR1147A	Up to Day 134
Volume of Distribution (V) 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
Maximum Serum Concentration (Cmax) of UTTR1147A After the First and Last Dose	Up to Day 134

Trial Locations

Locations (2)

Royal Victoria Infirmary; 🇬🇧 Newcastle upon Tyne, United Kingdom

Charité Research Organisation GmbH; 🇩🇪 Berlin, Germany