Novel treatment for systemic inflammation disorders such as endotoxemia and sepsis. Circulatory System
Conditions
Interventions
Part 1 and Part 2 volunteers will either receive sevuparin (low dose, intermediate dose or high dose) or placebo. This will be administered by IV infusion (bolus loading dose followed by continuous in
Sponsors
Modus Therapeutics (Sweden)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Healthy male and female volunteers aged 18 to 55 years, inclusive. Health status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, haematology, blood chemistry, and urinalysis; 2. BMI in the range of 18 to 30 kg/m², and a minimum body weight of 50 kg and a maximal body weight of 112 kg; 3. No history of trauma with likely damage to the spleen or surgery to spleen; 4. Free from any clinically significant febrile illness 30 days preceding study Day 1.
Exclusion criteria
Exclusion criteria: 1. History of sepsis, cardiovascular disease, syncope or malignancy; 2. Haemorrhagic diathesis (easy bruising, epistaxis, gastro-intestinal bleeding); 3. First degree family history of premature cardiovascular disease event (if diagnosed before 50 years of age); 4. Previous participation in a systemic (i.v./inhaled) LPS challenge trial or prior exposure to systemic endotoxin within a year before the first study day (applicable to Part 1 and 2 only) or previous exposure to sevuparin in study Part 1 or 2 (applicable to Part 3 only); 5. Subjects who have received any of the following excluded medications within prescribed 14 days of the first dose administration: aspirin, anti-platelet therapy, anticoagulant therapy and prophylactic and therapeutic LMWH or unfractioned heparin; 6. Subjects who have received prophylactic/therapeutic LMWH or unfractioned heparin within the last year; 7. Subjects who have any current and / or recurrent pathologically, clinically significant skin condition at the lower forearms (i.e. atopic dermatitis); including tattoos (applicable to Part 1 and 2 only).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1 (ID LPS) basal cutaneous perfusion measured using a laser speckle contrast imager on day -1, day 1 and day 2. Part 2 (IV LPS) safety and tolerability measured using the following: 2.1. Vital signs on day 1 to 3 and day 8 (up to day 10) 2.2. Treatment-Emergent Adverse Events on day 1 to day 8 (up to day 10) 2.3. Electrocardiography on day 1 to 2 and day 8 (up to day 10) 2.4. Haematology and chemistry blood panels, including heparin-induced thrombocytopenia antibodies, at day 1 to 3 and day 8 (up to day 10) 2.5. Subjective assessment of feeling sick on a numeric rating scale on day 1 and 2. Part 3 is to assess magnitude of any pharmacodynamic interactions in terms of coagulation parameters measured using APTT, PT, INR, fibrinogen, anti-factor Xa activity, anti-factor IIa activity and D-dimer concentration on day 1 and 2. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Changes in immune cells and inflammatory cytokines measured using flow cytometry and MesoScale Discovery from baseline up to 48 h post-dose (Part 1 and Part 2). 2. Safety and tolerability endpoints measured using vital signs, Treatment-Emergent Adverse Events, electrocardiography and haematology and chemistry blood panels, including heparin-induced thrombocytopenia antibodies (if indicated), at baseline and up to 8-10 days post-dose (Part 1 and Part 3). 3. Pharmacokinetic endpoints measured using a heparin red assay method at baseline and up to 24 h post-dose (Part 2). | — |
Countries
Netherlands
Outcome results
None listed