SCIENS: Studying Complement Inhibition in Early, Newly Developing Septic Organ Dysfunction

Sponsor

InflaRx GmbH (Industry)

Overall Status

Completed

CT.gov ID

NCT02246595

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

6.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Severe Sepsis Septic Shock	Biological: CaCP29 Biological: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

72 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2014

Actual Primary Completion Date :

Dec 1, 2015

Actual Study Completion Date :

Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: CaCP29 dose escalating i.v. administration of CaCP29 (verum)	Biological: CaCP29 Other Names: IFX-1
Placebo Comparator: Placebo dose escalation mimicing i.v. placebo treatment:	Biological: Placebo

Arm

Intervention/Treatment

Active Comparator: CaCP29

dose escalating i.v. administration of CaCP29 (verum)

Biological: CaCP29

Other Names:

IFX-1

Placebo Comparator: Placebo

dose escalation mimicing i.v. placebo treatment:

Biological: Placebo

Outcome Measures

Primary Outcome Measures

Plasma Concentration of CaCP29 [0h, 2h, 6h, 12h, 14h (only cohort 1), 24h, 26h (only cohort 2 and 3), 48h, 72h, 74h (only cohort 3), days 5, 8, 13, 28]
Pharmacokinetic measures include Plasma concentration over time Maximum observed concentration per infusion Concentration measured immediately before next dosing Area under the curve of plasma concentration per infusion Mean concentration per infusion Terminal phase half-life
Assess the pharmacodynamic (PD) effects of CaCP29 on the change from baseline in plasma concentrations of C5a [0h, 2h, 6h, 12h, 14h (only cohort 1), 24h, 26h (only cohort 2 and 3), 48h, 72h, 74h (only cohort 3), days 5, 8, 13, 28]
Safety variables will be summarized using descriptive statistics based on adverse event collection [28 days]

Secondary Outcome Measures

Anti-drug antibodies (ADA) [28 days or hospital discharge]
The development of ADA will be described by: Number of patients with detection of anti-drug antibody (ADA) Number of patients with detection of ADA at each time point measured
All-cause mortality rate [28 days]
Morbidity [daily]
Mean SOFA until Day 10 Modified mean SOFA until day 10 (calculated by omitting the Central Nervous System sub-score and calculating the renal subscore without taking urine output into consideration) Mean SOFA Sub-scores until Day 10 Days on ICU until Day 28 Number of patients ventilated until Day 14 Ventilator-free days until Day 14 Numbers of patients with renal replacement therapy (RRT) until Day 14 RRT-free days until Day 14 Numbers of patients with administration of vasopressor until Day 14 Vasopressor-free days until Day 14 Days without antimicrobial therapy (AMT) until Day 14
Fluid balance [28 days or ICU discharge]
Mean daily total fluid intake until Day 28 (maximal until ICU discharge) Mean daily total fluid output until Day 28 (maximal until ICU discharge) Mean daily fluid balance until Day 28 (maximal until ICU discharge)
Change in routine laboratory parameters as compared to baseline [Days 1, 2, 3, 4, 5, 8, 13, 28]
Change in ECG as compared to baseline [Days 2, 4, 8, 28]
Change in vital signs as compared to baseline [Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, Day 28]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria at screening:

Male or female patients >= 18 years old
Written informed consent
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
Suspected or confirmed abdominal or pulmonary infection at screening
Broad spectrum i.v. antimicrobial therapy to treat abdominal or pulmonary infection
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:
respiratory
renal
hematologic
metabolic
cardiovascular (occurred within the last three hours)
Reasonable likelihood that administration of study drug can be started within 3.5 hours after start of screening process

Key Exclusion Criteria at screening:

Sepsis of other primary cause than pulmonary or abdominal source
Weight > 130 kg at screening
Any other disease and condition that is likely to interfere with evaluation of study product, outcome assessment or satisfactory conduct of the study
Patients receiving the following concomitant medication within 14 days prior to screening:
Calcineurin inhibitors (e.g., ciclosporine, tacrolimus)
Proliferation inhibitors (e.g., everolimus, sirolimus)
Anti-metabolites (e.g., mycophenolate, mycophenolic acid, azathioprine)
High dose corticosteroids (e.g., > 50mg prednisolon per day or equivalent)
Patients receiving high dose immunoglobulins within 3 months prior to screening
Patients with following abnormal laboratory result: Neutrocytopenia with neutrophil count < 1,000/mm3 unless likely due to sepsis
General criteria:
Pregnant (in women of childbearing potential an urine pregnancy test has to be performed) or breast-feeding women
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
Participation in any interventional clinical trial within the last three months
Prior participation in this clinical trial
Patient is chronically bed-bound prior to the onset of sepsis
Known intravenous drug abuse
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
No commitment to full aggressive life support (e.g., do not resuscitate order)

Inclusion Criteria at randomisation:

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

Exclusion Criteria at randomisation:

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

Contacts and Locations

Locations

	Site	City	Country
1	Study Site	Aachen	Germany
2	Study Site	Augsburg	Germany
3	Study Site	Bad Saarow	Germany
4	Study Site	Berlin	Germany
5	Study Site	Greifswald	Germany
6	Study Site	Göttingen	Germany
7	Study Site	Hamburg	Germany
8	Study Site	Jena	Germany
9	Study Site	Kiel	Germany
10	Study Site	Leipzig	Germany
11	Study Site	Oldenburg	Germany