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

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ClinicalTrials.gov Identifier: NCT02246595
Recruitment Status : Completed
First Posted : September 23, 2014
Last Update Posted : April 25, 2016
Sponsor:
Information provided by (Responsible Party):
InflaRx GmbH

Tracking Information
First Submitted Date  ICMJE September 18, 2014
First Posted Date  ICMJE September 23, 2014
Last Update Posted Date April 25, 2016
Study Start Date  ICMJE April 2014
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 22, 2014)
  • Plasma Concentration of CaCP29 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 28 days ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 23, 2014)
  • Anti-drug antibodies (ADA) [ Time Frame: 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 [ Time Frame: 28 days ]
  • Morbidity [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Days 1, 2, 3, 4, 5, 8, 13, 28 ]
  • Change in ECG as compared to baseline [ Time Frame: Days 2, 4, 8, 28 ]
  • Change in vital signs as compared to baseline [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, Day 28 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 22, 2014)
  • Anti-drug antibodies (ADA) [ Time Frame: 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 [ Time Frame: 28 days ]
  • Morbidity [ Time Frame: 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 [ Time Frame: daily ]
    • 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 [ Time Frame: Days 1, 2, 3, 4, 5, 8, 13, 28 ]
  • Change in ECG as compared to baseline [ Time Frame: Days 2, 4, 8, 28 ]
  • Change in vital signs as compared to baseline [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, Day 28 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Studying Complement Inhibition in Early, Newly Developing Septic Organ Dysfunction
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Severe Sepsis
  • Septic Shock
Intervention  ICMJE
  • Biological: CaCP29
    Other Name: IFX-1
  • Biological: Placebo
Study Arms  ICMJE
  • Active Comparator: CaCP29
    dose escalating i.v. administration of CaCP29 (verum)
    Intervention: Biological: CaCP29
  • Placebo Comparator: Placebo
    dose escalation mimicing i.v. placebo treatment:
    Intervention: Biological: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 22, 2014)
72
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 2015
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02246595
Other Study ID Numbers  ICMJE IFX-1-P2.1
2013-001037-40 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party InflaRx GmbH
Study Sponsor  ICMJE InflaRx GmbH
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Michael Bauer, Prof. Dr. University Hospital Jena
PRS Account InflaRx GmbH
Verification Date April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP