E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe sepsis and/or septic shock |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040047 |
E.1.2 | Term | Sepsis |
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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 primary objective is to evaluate the effect of two different doses of AZD9773 (CytoFab™) versus placebo on ventilator free days (VFDs) over 28 days in patients with severe sepsis and/or septic shock, who are receiving appropriate standard of care.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate the effect of two different doses of AZD9773 versus placebo in patients with severe sepsis and/or septic shock on 7 day and 28 day mortality, the safety profile, morbidity, mortality at Day 90, health related Quality of Life (QoL) and the biological effect on plasma tumour necrosis factor alfa (TNFα) levels and relevant cytokines. There will also be an attempt to determine the population pharmacokinetics (PK) of AZD9773 and to assess the relationship between PK and measures of pharmacodynamic (PD) response, efficacy and adverse events (AEs) in patients with severe sepsis and/or septic shock.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adults with a first episode of sepsis during this hospitalisation. 2. Objective clinical evidence of infection. 3. At least 2 of 4 SIRS criteria in the 24 hours before organ dysfunction (must include either fever OR elevated white blood cells [WBC]). 4. Cardiovascular and/or respiratory dysfunction.
Note: complete details are listed in Section 5.1 of the protocol. |
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E.4 | Principal exclusion criteria |
1. Moribund (not likely to survive 24 hours) or significant comorbidities making survival for 3 months unlikely. 2. Immunocompromising comorbidities or concomitant medications. • Advanced human immunodeficiency virus (HIV) infection (CD4 ≤50/mm3). • Stage III or IV cancer. • Haemopoietic or lymphoreticular malignancies not in remission. • Receiving radiation therapy or chemotherapy. • Stem cell, organ or bone marrow transplant in the past 6 months. • Absolute neutrophil count <500 per μL. • Doses of some steroids and some immunocompromising drugs. 3. Concomitant diseases: • Deep seated fungal infection or active tuberculosis. • Cirrhosis with portal hypertension or Childs-Pugh Class C. • History of chronic hypercarbia, respiratory failure in past 6 months or use of • home oxygen in the setting of severe chronic respiratory disease. • Neuromuscular disorders that impact breathing/spontaneous ventilation. • Quadriplegia. • Cardiac arrest in the past 30 days. • New York Heart Association functional Class IV due to heart failure or any disorder. • Burns over > 30% of body surface area. 4. Medication and allergy disqualifications. • Treatment with anti-TNF agents within the last 8 weeks. • Previously received ovine derived products (CroFab™, DigiFab™). • Sheep product allergy or allergy to latex, papain, chymopapain. 5. Pregnancy or plans to breast feed upon resolution of sepsis.
Note: complete details are listed in Section 5.2 of the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Ventilator free days over the 28 day study period |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | Yes |
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.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 18 |
E.8.9.2 | In all countries concerned by the trial days | 0 |