Sepsis Septic shock
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
Sponsors
Modus therapeutics Inc.
Eligibility
Age
18 Years to 64 Years
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, a minimum body weight of 50 kg and a maximum body weight of 112 kg; 3. Be able to abstain from smoking from 24 hours prior to dosing until study discharge visit; 4. No history of alcohol or drug abuse; 5. No history of trauma with likely damage to the spleen or surgery to spleen; 6. Free from any clinically significant febrile illness 30 days preceding study Day 1; 7. Non-atopic constitution, including non-asthmatic; 8. Fitzpatrick skin type I-III (applicable to Part 1 and 2 only); 9. No use of any prescription drugs, including aspirin or other non-steroid anti-inflammatory drugs; 10. Able to give written informed consent and willing to comply with all study-related procedures; 11. Female subjects of childbearing potential and male subjects who have sexual intercourse with a woman of childbearing potential must be willing to practice effective contraception during the study and be willing and able to continue contraception for at least 90 days after their last dose of study treatment. Women of childbearing potential are defined as all women physiologically capable of becoming pregnant, unless they meet one of the following conditions: • Postmenopausal: 12 months of natural (spontaneous) amenorrhea or 6 weeks after surgical bilateral oophorectomy with or without hysterectomy; • Posthysterectomy. For the purposes of the study, effective contraception is defined as follows: • Females: Using 1 or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation), intrauterine contraception/device, hormonal contraception, or any 2 barrier methods (a combination of male or female condom with diaphragm, sponge or cervical cap). • Males: Effective male contraception includes a vasectomy with negative semen analysis at follow up, or the use of condoms. Abstinence can be considered an acceptable method of contraception at the discretion of the investigator. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not considered acceptable methods of contraception.
Exclusion criteria
Exclusion criteria: 1. History of sepsis or history of clinically significant 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 un-fractioned heparin 6. Subjects who have received prophylactic/therapeutic LMWH or un-fractioned 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). 8. Subject is female and is pregnant (based upon serum pregnancy test at screening and urine pregnancy test pre-dose to the first sevuparin/placebo administration), breast-feeding, or planning to become pregnant during the study or within 90 days after last dose of study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1 • Microvascular function - Laser speckle contrast imaging, basal flow and with heating protocol - Multispectral imaging • Blister exudate - Flow cytometry (Neutrophils, monocyte subsets, T cells, B cells, NK cells, dendritic cells) - Cytokines (including IL-1b, IL-6, IL-8 and TNF-a) • Safety and tolerability - Vital signs - Treatment-Emergent Adverse Events - Electrocardiography - Haematology and chemistry blood panels, including HIT antibodies Part 2 • Microvascular function - Laser speckle contrast imaging, with heating protocol - Sidestream Darkfield Imaging - Passive limb movement • Blood - Leucocyte differential - Cytokines (including IL-6, IL-8, IL-10 and TNF-a) - Flow cytometry (Neutrophils, monocyte subsets, T cells, B cells, NK cells, dendritic cells, including neutrophil extracellular traps) - Explorative biomarkers: acute phase reactants and components measurable in blood, serum and plasma of relevance for septic inflammation may be measured and reported separately. • Pharmacokinetics • Safety and tolerability - Vital signs - Treatment-Emergent Adverse Events - Electrocardiography - Haematology and chemistry blood panels, including HIT antibodies - NRS (self-rated sickness feeling) Part 3 • Coagulation parameters (including APTT, PT, INR, anti-fXa, anti-fIIa and D-dimer) • Safety and tolerability - Vital signs - Treatment-Emergent Adverse Events - Electrocardiography - Haematology and chemistry blood panels, including HIT antibodies | — |
Countries
Netherlands
Outcome results
None listed