Studying Complement Inhibition in Early, Newly Developing Septic Organ Dysfunction

NCT02246595 | Completed Phase 2 DMC

• 2 other identifiers: IFX-1-P2.12013-001037-40
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 11

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.

Conditions

Severe Sepsis; Septic Shock

Keywords

Sepsis; Severe Sepsis; Septic Shock; Systemic Inflammatory Response Syndrome; Organ Dysfunction

Outcome Measures

Primary Outcomes (3)

• Plasma Concentration of CaCP29

  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

  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

• 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 Outcomes (7)

• Anti-drug antibodies (ADA)

  28 days or hospital discharge

• All-cause mortality rate

  28 days

• Morbidity

  daily

• Fluid balance

  28 days or ICU discharge

• Change in routine laboratory parameters as compared to baseline

  Days 1, 2, 3, 4, 5, 8, 13, 28

Study Arms (2)

CaCP29

ACTIVE COMPARATOR

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

Biological: CaCP29

Placebo

PLACEBO COMPARATOR

dose escalation mimicing i.v. placebo treatment:

Biological: Placebo

Interventions

CaCP29 BIOLOGICAL

Also known as: IFX-1

CaCP29

Placebo BIOLOGICAL

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• InflaRx GmbH: lead

Study Sites (11)

Study Site

Aachen, Germany

Location

Study Site

Augsburg, Germany

Location

Study Site

Bad Saarow, Germany

Location

Study Site

Berlin, Germany

Location

Study Site

Göttingen, Germany

Location

Study Site

Greifswald, Germany

Location

Study Site

Hamburg, Germany

Location

Study Site

Jena, Germany

Location

Study Site

Kiel, Germany

Location

Study Site

Leipzig, Germany

Location

Study Site

Oldenburg, Germany

Location

MeSH Terms

Conditions

Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome

Interventions

vilobelimab

Condition Hierarchy (Ancestors)

Infections; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Michael Bauer, Prof. Dr.

  University Hospital Jena

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2014
• First Posted: September 23, 2014
• Study Start: April 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: April 25, 2016

Record last verified: 2016-04

Locations

DE (11)