Clinical trial NCT06298032: A Study Investigating the Safety, Tolerability, Immunogenicity and Pharmacokinetics of Olamkicept in Healthy Persons
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Inflammatory Gastrointestinal Diseases
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-03-07
Enrollment: 49
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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).

Primary outcomes:
measure: Number of treatment-emergent adverse events, including type, intensity, and causality
timeFrame: End of trial (up to 64 days)
measure: Change in vital signs from baseline to Day 36 after a single dose infusion
timeFrame: From baseline up to and including Day 36 after a single dose infusion
measure: Change in vital signs from baseline to Day 64 after multiple dose infusions
timeFrame: From baseline up to and including Day 64 after multiple dose infusions
measure: Change in 12-lead electrocardiogram (ECG) from baseline to Day 36 after a single dose infusion
timeFrame: From baseline up to and including Day 36 after a single dose infusion
measure: Change in 12-lead electrocardiogram (ECG) from baseline to Day 64 after multiple dose infusions
timeFrame: From baseline up to and including Day 64 after multiple dose infusions
measure: Change in haematology from baseline to Day 36 after a single dose infusion
timeFrame: From baseline to Day 36 after a single dose infusion
measure: Change in haematology from baseline to Day 64 after multiple dose infusions
timeFrame: From baseline to Day 64 after multiple dose infusions
measure: Change in clinical chemistry from baseline to Day 36 after a single dose infusion
timeFrame: From baseline to Day 36 after a single dose infusion
measure: Change in clinical chemistry from baseline to Day 64 after multiple dose infusions
timeFrame: From baseline up to and including Day 64 after multiple dose infusions
measure: Change in haemostasis parameters from baseline to Day 36 after a single dose infusion
timeFrame: From baseline up to and including Day 36 after a single dose infusion
measure: Change in haemostasis parameters from baseline to Day 64 after multiple dose infusions
timeFrame: From baseline up to and including Day 64 after multiple dose infusions
measure: Change in urinalysis parameters from baseline to Day 36 after a single dose infusion
timeFrame: From baseline to Day 36 after a single dose infusion
measure: Change in urinalysis parameters from baseline to Day 64 after multiple dose infusions
timeFrame: From baseline up to and including Day 64 after multiple dose infusions
Secondary outcomes:
measure: Single-dose PK of FE 999301: Area under the concentration-time curve from dosing to infinity (AUCinf)
timeFrame: From baseline up to and including Day 36 after a single dose infusion
measure: Single-dose PK of FE 999301: Area under the concentration-time curve to last measurable concentration (AUClast)
timeFrame: From baseline up to and including Day 36 after a single dose infusion
measure: Single-dose PK of FE 999301: Observed plasma concentration at end of infusion (AUCeoi)
timeFrame: From baseline up to and including Day 36 after a single dose infusion
measure: Single-dose PK of FE 999301: Baseline adjusted maximum observed concentration; also referred to as maximum exposure (Cmax)
timeFrame: From baseline up to and including Day 36 after a single dose infusion
measure: Single-dose PK of FE 999301: Time of maximum observed concentration (tmax)
timeFrame: From baseline up to and including Day 36 after a single dose infusion
measure: Single-dose PK of FE 999301: Terminal half-life (t1/2)
timeFrame: From baseline up to and including Day 36 after a single dose infusion
measure: Single-dose PK of FE 999301: Mean residence time (MRT)
timeFrame: From baseline up to and including Day 36 after a single dose infusion
measure: Single-dose PK of FE 999301: Total clearance (CL)
timeFrame: From baseline up to and including Day 36 after a single dose infusion
measure: Single-dose PK of FE 999301: Apparent volume of distribution at steady-state (Vss)
timeFrame: From baseline up to and including Day 36 after a single dose infusion
measure: Multiple-dose PK of FE 999301: Area under concentration-time curve from dosing up to time τ, where τ is the dosing interval (AUCτ)
timeFrame: From baseline up to and including Day 64 after a multiple dose infusions
measure: Multiple-dose PK of FE 999301: Area under the concentration-time curve to last measurable concentration (AUClast)
timeFrame: From baseline up to and including Day 64 after a multiple dose infusions
measure: Multiple-dose PK of FE 999301: Observed accumulation index (Rac)
timeFrame: From baseline up to and including Day 64 after a multiple dose infusions
measure: Multiple-dose PK of FE 999301: Observed plasma concentration at end of infusion (Ceio)
timeFrame: From baseline up to and including Day 64 after a multiple dose infusions
measure: Multiple-dose PK of FE 999301: Baseline adjusted maximum observed concentration; also referred to as maximum exposure (Cmax)
timeFrame: From baseline up to and including Day 64 after a multiple dose infusions
measure: Multiple-dose PK of FE 999301: Time of maximum observed concentration (tmax)
timeFrame: From baseline up to and including Day 64 after a multiple dose infusions
measure: Multiple-dose PK of FE 999301: Terminal half-life (t½)
timeFrame: From baseline up to and including Day 64 after a multiple dose infusions
measure: Multiple-dose PK of FE 999301: Mean residence time (MRT)
timeFrame: From baseline up to and including Day 64 after a multiple dose infusions
measure: Multiple-dose PK of FE 999301: Total clearance (CL)
timeFrame: From baseline up to and including Day 64 after a multiple dose infusions
measure: Multiple-dose PK of FE 999301: Apparent volume of distribution at steady-state (Vss)
timeFrame: Day 64
measure: Presence of anti-FE 999301 antibodies on Days 1, 15, and 57 after multiple dose infusions
timeFrame: On Days 1, 15, and 57 after multiple dose infusions
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Ferring Investigational Site
Study officials:
affiliation: Ferring Pharmaceuticals
name: Global Clinical Compliance
role: STUDY_DIRECTOR
References: