A Study Investigating the Safety, Tolerability, Immunogenicity and Pharmacokinetics of Olamkicept in Healthy Persons

Ferring Pharmaceuticals49 enrolled

Overview

Interleukin (IL)-6 is a cytokine produced in response to infection and tissue damage. IL-6 is believed to act as a key mediator in chronic inflammation and autoimmune diseases such as inflammatory bowel diseases. IL-6 is known to be involved in at least two distinct signalling pathways, classical and trans-signalling. The hypothesis is that classical signalling by IL-6 infers some beneficial effects (e.g. on gut barrier function), while excessive IL-6 trans-signalling may have detrimental effects. Olamkicept (FE 999301) has been shown in vitro to be a selective IL-6 trans-signalling inhibitor, and administered at lower doses (600 mg every 2nd week for 12 weeks) it has proven to induce clinical improvement for patients with ulcerative colitis. The aim of this trial is to investigate safety, tolerability, immunogenicity and pharmacokinetics of Olamkicept at higher doses (up to 2400 mg) to support the clinical development program. Our hypothesis is that treatment with higher doses of Olamkicept will result in greater clinical improvement for patients with inflammatory bowel diseases.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Inflammatory Gastrointestinal Diseases

Interventions

Eligibility

Sex: MALEMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Men ≥18 and ≤45 years of age at screening * In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), vital signs measurements, and clinical laboratory evaluations, as assessed by the investigator (or designee) at screening and on Day -1 Exclusion Criteria: * History of clinically significant medical conditions including, but not limited to, diseases of the renal, hepatic, respiratory, gastrointestinal, cardiovascular, neurological, musculoskeletal, psychiatric, immunological, haematological, oncological, endocrine, and metabolic systems and allergic diseases (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).

Outcomes

Primary Outcomes

Number of treatment-emergent adverse events, including type, intensity, and causality

Time frame: End of trial (up to 64 days)

Change in vital signs from baseline to Day 36 after a single dose infusion

Number of participants with clinically significant abnormal findings in vital signs (systolic blood pressure, diastolic blood pressure, pulse, body temperature), from baseline up to and including Day 36 after a single dose infusion (part A of the study).

Time frame: From baseline up to and including Day 36 after a single dose infusion

Change in vital signs from baseline to Day 64 after multiple dose infusions

Number of participants with clinically significant abnormal findings in vital signs (systolic blood pressure, diastolic blood pressure, pulse, body temperature), from baseline up to and including Day 64 after multiple dose infusions (part B of the study)

Time frame: From baseline up to and including Day 64 after multiple dose infusions

Change in 12-lead electrocardiogram (ECG) from baseline to Day 36 after a single dose infusion

Number of participants with clinically significant abnormal findings in ECG (heart rate, PR interval, RR, QRS duration, QT interval, QTc interval, QRS axis), from baseline up to and including Day 36 after a single dose infusion (part A of the study)

Time frame: From baseline up to and including Day 36 after a single dose infusion

Change in 12-lead electrocardiogram (ECG) from baseline to Day 64 after multiple dose infusions

Number of participants with clinically significant abnormal findings in ECG (heart rate, PR interval, RR, QRS duration, QT interval, QTc interval, QRS axis), from baseline up to and including Day 64 after multiple dose infusions (part B of the study)

Time frame: From baseline up to and including Day 64 after multiple dose infusions

Change in haematology from baseline to Day 36 after a single dose infusion

Number of participants with clinically significant abnormal findings in haematology (haematocrit, haemoglobin, mean cellular volume (MCV), mean corpuscular haemoglobin content (MCH), mean corpuscular haemoglobin concentration (MCHC), platelet count, red blood cell count, reticulocytes, white blood cell count with differential count, neutrophils, eosinophils, basophils, lymphocytes, monocytes), from baseline up to and including Day 36 after a single dose infusion (part A of the study)

Time frame: From baseline to Day 36 after a single dose infusion

Change in haematology from baseline to Day 64 after multiple dose infusions

Number of participants with clinically significant abnormal findings in haematology (haematocrit, haemoglobin, mean cellular volume (MCV), mean corpuscular haemoglobin content (MCH), mean corpuscular haemoglobin concentration (MCHC), platelet count, red blood cell count, reticulocytes, white blood cell count with differential count, neutrophils, eosinophils, basophils, lymphocytes, monocytes), from baseline up to and including Day 64 after multiple dose infusions (part B of the study)

Time frame: From baseline to Day 64 after multiple dose infusions

Change in clinical chemistry from baseline to Day 36 after a single dose infusion

Number of participants with clinically significant abnormal findings in clinical chemistry (alanine aminotransferase (ALT), albumin, alkaline phosphatase, aspartate aminotransferase (AST), glucose, calcium, chloride, cholesterol, C-reactive protein, creatinine, estimated glomerular filtration rate (eGFR), gamma-glutamyltransferase, phosphate, potassium, sodium, thyroid stimulating hormone, free triiodothyronine, free thyroxine, total bilirubin, urea (blood urea nitrogen)), from baseline up to and including Day 36 after a single dose infusion (part A of the study)

Time frame: From baseline to Day 36 after a single dose infusion

Change in clinical chemistry from baseline to Day 64 after multiple dose infusions

Number of participants with clinically significant abnormal findings in clinical chemistry (alanine aminotransferase (ALT), albumin, alkaline phosphatase, aspartate aminotransferase (AST), glucose, calcium, chloride, cholesterol, C-reactive protein, creatinine, estimated glomerular filtration rate (eGFR), gamma-glutamyltransferase, phosphate, potassium, sodium, thyroid stimulating hormone, free triiodothyronine, free thyroxine, total bilirubin, urea (blood urea nitrogen)), from baseline up to and including Day 64 after multiple dose infusions (part B of the study)

Time frame: From baseline up to and including Day 64 after multiple dose infusions

Change in haemostasis parameters from baseline to Day 36 after a single dose infusion

Number of participants with clinically significant abnormal findings in haemostasis parameters (activated partial thromboplastin time, prothrombin time) from baseline up to and including Day 36 after a single dose infusion (part A of the study)

Time frame: From baseline up to and including Day 36 after a single dose infusion

Change in haemostasis parameters from baseline to Day 64 after multiple dose infusions

Number of participants with clinically significant abnormal findings in haemostasis parameters (activated partial thromboplastin time, prothrombin time) from baseline up to and including Day 64 after multiple dose infusions (part B of the study)

Time frame: From baseline up to and including Day 64 after multiple dose infusions

Change in urinalysis parameters from baseline to Day 36 after a single dose infusion

Number of participants with clinically significant abnormal findings in urinalysis parameters (protein, glucose, bilirubin, pH, nitrite, ketone, urobilinogen, blood, leukocytes, specific gravity) from baseline up to and including Day 36 after a single dose infusion (part A of the study)

Time frame: From baseline to Day 36 after a single dose infusion

Change in urinalysis parameters from baseline to Day 64 after multiple dose infusions

Number of participants with clinically significant abnormal findings in urinalysis parameters (protein, glucose, bilirubin, pH, nitrite, ketone, urobilinogen, blood, leukocytes, specific gravity) from baseline up to and including Day 64 after multiple dose infusions (part B of the study)

Time frame: From baseline up to and including Day 64 after multiple dose infusions

Secondary Outcomes

Single-dose PK of FE 999301: Area under the concentration-time curve from dosing to infinity (AUCinf)

Time frame: From baseline up to and including Day 36 after a single dose infusion

Single-dose PK of FE 999301: Area under the concentration-time curve to last measurable concentration (AUClast)

Time frame: From baseline up to and including Day 36 after a single dose infusion

Single-dose PK of FE 999301: Observed plasma concentration at end of infusion (AUCeoi)

Time frame: From baseline up to and including Day 36 after a single dose infusion

Single-dose PK of FE 999301: Baseline adjusted maximum observed concentration; also referred to as maximum exposure (Cmax)

Time frame: From baseline up to and including Day 36 after a single dose infusion

Single-dose PK of FE 999301: Time of maximum observed concentration (tmax)

Time frame: From baseline up to and including Day 36 after a single dose infusion

Single-dose PK of FE 999301: Terminal half-life (t1/2)

Time frame: From baseline up to and including Day 36 after a single dose infusion

Single-dose PK of FE 999301: Mean residence time (MRT)

Time frame: From baseline up to and including Day 36 after a single dose infusion

Single-dose PK of FE 999301: Total clearance (CL)

Time frame: From baseline up to and including Day 36 after a single dose infusion

Single-dose PK of FE 999301: Apparent volume of distribution at steady-state (Vss)

Time frame: From baseline up to and including Day 36 after a single dose infusion

Multiple-dose PK of FE 999301: Area under concentration-time curve from dosing up to time τ, where τ is the dosing interval (AUCτ)

A Study Investigating the Safety, Tolerability, Immunogenicity and Pharmacokinetics of Olamkicept in Healthy Persons

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes