Studying Complement Inhibition in Early, Newly Developing Septic Organ Dysfunction

A Phase II Randomized, Placebo-controlled, Double-blind, Dose Controlled Trial in Patients Suffering From Early, Newly Developing Abdominal or Pulmonary Derived Septic Organ Dysfunction to Evaluate Safety, Pharmacokinetics, Pharmacodynamics and to Estimate Efficacy of the New Humanized Monoclonal i.v. Administered Antibody CaCP29

The trial enrolls patients with early severe sepsis or septic shock displaying at least one newly developed organ dysfunction and showing clinical evidence of pulmonary or abdominal infection. The primary goal of the trial is to assess the pharmacokinetics and pharmacodynamics of the new monoclonal antibody CaCP29 and to characterize safety and tolerability as well as evaluate parameters of efficacy.

Key Inclusion Criteria at screening:

1. Male or female patients >= 18 years old

2. Written informed consent

3. Occurrence of at least two criteria of a systemic inflammatory response syndrome (SIRS) not explained by other reasons. These criteria should be present within 12 hours prior to screening

4. Suspected or confirmed abdominal or pulmonary infection at screening

5. Broad spectrum i.v. antimicrobial therapy to treat abdominal or pulmonary infection

6. At least one of the following acute organ dysfunctions due to sepsis. Each organ dysfunction must have occurred within 12 hours prior to screening, cannot mainly be explained by other disease processes than sepsis and is judged by the investigator as being caused or directly related to an abdominal or pulmonary infectious focus:

   1. respiratory
   2. renal
   3. hematologic
   4. metabolic
   5. cardiovascular (occurred within the last three hours)

7. Reasonable likelihood that administration of study drug can be started within 3.5 hours after start of screening process

Key Exclusion Criteria at screening:

1. Sepsis of other primary cause than pulmonary or abdominal source

2. Weight > 130 kg at screening

3. Any other disease and condition that is likely to interfere with evaluation of study product, outcome assessment or satisfactory conduct of the study

4. Patients receiving the following concomitant medication within 14 days prior to screening:

   1. Calcineurin inhibitors (e.g., ciclosporine, tacrolimus)
   2. Proliferation inhibitors (e.g., everolimus, sirolimus)
   3. Anti-metabolites (e.g., mycophenolate, mycophenolic acid, azathioprine)
   4. High dose corticosteroids (e.g., > 50mg prednisolon per day or equivalent)

5. Patients receiving high dose immunoglobulins within 3 months prior to screening

6. Patients with following abnormal laboratory result: Neutrocytopenia with neutrophil count < 1,000/mm3 unless likely due to sepsis

7. General criteria:

   1. Pregnant (in women of childbearing potential an urine pregnancy test has to be performed) or breast-feeding women
   2. Women with childbearing potential (defined as within two years of their last menstruation) not willing to practice appropriate contraceptive measures (e.g., implanon, injections, oral contraceptives, intrauterine devices, partner with vasectomy, abstinence) while participating in the trial
   3. Participation in any interventional clinical trial within the last three months
   4. Prior participation in this clinical trial
   5. Patient is chronically bed-bound prior to the onset of sepsis
   6. Known intravenous drug abuse
   7. Employee at the study site, spouse/partner or relative of any study staff (e.g., investigator, sub-investigators, or study nurse) or relationship to the sponsor
   8. No commitment to full aggressive life support (e.g., do not resuscitate order)

Inclusion Criteria at randomisation:

1. At least one of the sepsis related organ dysfunction detected at screening is still present
2. Current treatment with broad spectrum i.v. antibiotics has been started or is ongoing

Exclusion Criteria at randomisation:

1. Time frame between detection of a non cardiovascular organ dysfunction and start of randomization procedure is more than 15 hours
2. Time frame between detection of a cardiovascular organ dysfunction and start of randomization is more than six hours
3. Organ dysfunctions are unlikely to be persistent for next three hours