E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Inflammation, SIRS and endotoxemia |
|
E.1.1.1 | Medical condition in easily understood language |
Inflammation, SIRS and endotoxemia |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061218 |
E.1.2 | Term | Inflammation |
E.1.2 | System Organ Class | 10018065 - General disorders and administration site conditions |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060412 |
E.1.2 | Term | Septicaemia due to Escherichia coli (E. coli) |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051553 |
E.1.2 | Term | Complement factor C1 |
E.1.2 | System Organ Class | 100000004848 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10040047 |
E.1.2 | Term | Sepsis |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10062357 |
E.1.2 | Term | SIRS |
E.1.2 | System Organ Class | 10018065 - General disorders and administration site conditions |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The effect of C1-INH prior to induction of a systemic inflammation by endotoxin (E. coli lipopolysaccharide), on the leukocyte
phenotype, activation and mobilization.
|
|
E.2.2 | Secondary objectives of the trial |
- Determine the effect of C1-esterase inhibition on the LPS induced pro-inflammatory response (IL-6, TNF-α and IL-1β) and increase of anti-inflammatory response (IL-10).
- Determination of neutrophil lifespans in blood, and post-mitotic pool transit times. These lifespans will be compared between healthy volunteers treated with or without C1-INH before LPS treatment. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age ≥ 18 and ≤ 35 years
Male
Healthy |
|
E.4 | Principal exclusion criteria |
Use of any medication
Congenital or acquired C1 inhibitory deficiency
Immune deficiency
Chronic inflammatory diseases
Smoking
History of allergic reaction to blood products
History, signs or symptoms of cardiovascular diseases
(Family) history of cerebrovasculair diseases under the age of 65 years
Previous vagal collaps
Hypertension (defined as RR systolic > 160 or RR diastolic > 90)
Hypotension (defined as RR systolic < 100 or RR diastolic < 50)
Renal impairment (defined as plasma creatinin > 120 μmol/l)
Liver enzyme abnormalities |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Main study endpoint is the phenotype of circulating neutrophils after LPS in the absence and presence of C1 INH substitution |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Before administration of C1-INH/placebo
Before administration of LPS
1h, 3h, 4.5h, 6h and 8h after LPS injection |
|
E.5.2 | Secondary end point(s) |
- Concentration of circulating cytokines after LPS in the absence and presence of C1 INH substitution.
- Study the possible differences between the circulatory and post-mitotic pool transit times of neutrophils in human blood in volunteers with and without C1-INH.
- Pharmacokinetic and pharmacodynamic data will be collected with respect to the anti-inflammatory effects of C1 INH.
- Effects on the PMN phenotype and function will be determined.
- C1 INH concentration and activity as well as anaphylatoxin concentrations will be measured and compared to baseline values. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Before administration of C1-INH/placebo
Before administration of LPS
1h, 3h, 4.5h, 6h and 8h after LPS injection |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |