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

A Placebo-controlled, Within-group Randomised, and Double-blind Trial Investigating Safety, Tolerability, and Pharmacokinetics of FE 999301 After Ascending Single and Multiple Doses in Healthy Subjects

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 Overview

• Status: Completed
• Conditions: Inflammatory Gastrointestinal Diseases
• Intervention / Treatment: Drug: Placebo; Drug: Olamkicept Part A; Drug: Olamkicept Part B

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Ferring Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Olamkicept - Part A	Drug: Olamkicept Part A; Intravenous infusion. Single dose. Part A consists of 3 different doses; 1200 mg; 1800 mg; 2400 mg; Other Names: FE 999301
Placebo Comparator: Placebo - Part A	Drug: Placebo; Intravenous infusion
Experimental: Olamkicept - Part B	Drug: Olamkicept Part B; Intravenous infusion. Multiple doses. Part B consists of 3 different doses.; 1200 mg; 1800 mg; 2400 mg; Other Names: FE 999301
Placebo Comparator: Placebo - Part B	Drug: Placebo; Intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of treatment-emergent adverse events, including type, intensity, and causality		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).	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)	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)	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)	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)	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)	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)	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)	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)	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)	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)	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)	From baseline up to and including Day 64 after multiple dose infusions

Secondary Outcome Measures

Outcome Measure	Time Frame
Single-dose PK of FE 999301: Area under the concentration-time curve from dosing to infinity (AUCinf)	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)	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)	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)	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)	From baseline up to and including Day 36 after a single dose infusion
Single-dose PK of FE 999301: Terminal half-life (t1/2)	From baseline up to and including Day 36 after a single dose infusion
Single-dose PK of FE 999301: Mean residence time (MRT)	From baseline up to and including Day 36 after a single dose infusion
Single-dose PK of FE 999301: Total clearance (CL)	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)	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)	From baseline up to and including Day 64 after a multiple dose infusions
Multiple-dose PK of FE 999301: Area under the concentration-time curve to last measurable concentration (AUClast)	From baseline up to and including Day 64 after a multiple dose infusions
Multiple-dose PK of FE 999301: Observed accumulation index (Rac)	From baseline up to and including Day 64 after a multiple dose infusions
Multiple-dose PK of FE 999301: Observed plasma concentration at end of infusion (Ceio)	From baseline up to and including Day 64 after a multiple dose infusions
Multiple-dose PK of FE 999301: Baseline adjusted maximum observed concentration; also referred to as maximum exposure (Cmax)	From baseline up to and including Day 64 after a multiple dose infusions
Multiple-dose PK of FE 999301: Time of maximum observed concentration (tmax)	From baseline up to and including Day 64 after a multiple dose infusions
Multiple-dose PK of FE 999301: Terminal half-life (t½)	From baseline up to and including Day 64 after a multiple dose infusions
Multiple-dose PK of FE 999301: Mean residence time (MRT)	From baseline up to and including Day 64 after a multiple dose infusions
Multiple-dose PK of FE 999301: Total clearance (CL)	From baseline up to and including Day 64 after a multiple dose infusions
Multiple-dose PK of FE 999301: Apparent volume of distribution at steady-state (Vss)	Day 64
Presence of anti-FE 999301 antibodies on Days 1, 15, and 57 after multiple dose infusions	On Days 1, 15, and 57 after multiple dose infusions

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals
• Investigators: Study Director: Global Clinical Compliance, Ferring Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2024
• Primary Completion (Actual): November 15, 2024
• Study Completion (Actual): November 15, 2024

Study Registration Dates

• First Submitted: February 1, 2024
• First Submitted That Met QC Criteria: March 6, 2024
• First Posted (Actual): March 7, 2024

Study Record Updates

• Last Update Posted (Estimated): November 19, 2024
• Last Update Submitted That Met QC Criteria: November 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Gastrointestinal Diseases; Digestive System Diseases
• Other Study ID Numbers: 000414

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No