Clinical trial NCT02749630: A Safety Study of Intravenously Administered UTTR1147A in Healthy Volunteers (HVs), Participants With Ulcerative Colitis (UC), and Participants With Crohn's Disease (CD)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ulcerative Colitis
Crohn's Disease
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2016-04-25
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants with Adverse Events
timeFrame: Up to Day 134
Secondary outcomes:
measure: Maximum Serum Concentration (Cmax) of UTTR1147A After the First and Last Dose
timeFrame: Up to Day 134
measure: Minimum (Trough) Serum Concentrations (Ctrough) of UTTR1147A Prior to the Second and Last Dose
timeFrame: Up to Day 134
measure: Total Serum Clearance (CL) of UTTR1147A
timeFrame: Up to Day 134
measure: Volume of Distribution (V) of UTTR1147A
timeFrame: Up to Day 134
measure: Area Under the Concentration vs. Time Curve (AUC) Within a Dose Interval (AUCtau) After the Final Dose of UTTR1147A
timeFrame: Up to Day 134
measure: Elimination Half-Life (t1/2) of UTTR1147A
timeFrame: Up to Day 134
measure: Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) in Serum
timeFrame: Up to Day 134
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Research Organisation GmbH
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.