A Phase 2 Study of IC14 in Acute Respiratory Distress Syndrome

Phase 2

Withdrawn

• Conditions: Acute Respiratory Distress Syndrome
• Interventions: Drug: IC14; Other: Placebo

• Registration Number: NCT03017547
• Lead Sponsor: Implicit Bioscience

Brief Summary

Acute Respiratory Distress Syndrome (ARDS) patients will be randomized to receive either IC14 (a single dose of 4 mg/kg followed by 2 mg/kg on Days 2-4) or placebo. Study participation will be for a total of 28 days.

Detailed Description

Up to 160 patients with ARDS will be randomized to receive either IC14 at a dosage of 4 mg/kg on Study Day 1, then 2 mg/kg once daily on Study Days 2-4 or placebo for 4 days beginning within 48 hours of meeting inclusion criteria. Study participation will be for 28 days.

Study Timeline

• Study First Submitted: 2017-01-09
• Study First Submitted QC: 2017-01-09
• Study First Posted: 2017-01-11
• Status Verified: 2018-05
• Last Update Submitted: 2019-03-12
• Last Update Posted: 2019-03-14
• Study Start: 2019-06
• Primary Completion: 2020-06
• Study Completion: 2020-06

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. ICU admission

2. Age 18-70 years

3. Presence of a known ARDS clinical risk within 7 days of onset:

   1. Pneumonia
   2. Sepsis
   3. Trauma
   4. Aspiration
   5. Pancreatitis

4. Presence of ARDS (per Berlin criteria) defined as follows:

   1. Acute onset (<48 hours)
   2. PaO2/FiO2<300 on PEEP≥5
   3. Bilateral opacities consistent with pulmonary edema on frontal chest radiograph not fully explained by effusions, lobar/lung collapse, or nodules.
   4. Requirement for positive pressure ventilation via endotracheal tube

5. Anticipated duration of mechanical ventilation >48 hrs

Exclusion Criteria

1. Treatment with a drug or device within the last 30 days that has not received regulatory approval at the time of study entry

2. Intubation for cardiopulmonary arrest

3. Do-not-attempt resuscitation (DNAR) status

4. Intubation for status asthmaticus, pulmonary embolus, myocardial infarction

5. Anticipated survival <48 hours from intubation

6. Anticipated survival <28 days due to pre-existing medical condition

7. Significant pre-existing organ dysfunction

   1. Lung: Currently receiving home oxygen therapy as documented in medical record
   2. Heart: Pre-existing congestive heart failure defined as an ejection fraction <20% as documented in the medical record
   3. Renal: Chronic renal failure requiring renal replacement therapy
   4. Liver: Severe chronic liver disease defined as Child-Pugh Class C

8. Pre-existing, ongoing immunosuppression

   1. Solid organ transplant recipient
   2. Chronic high-dose corticosteroids (equivalent to >20 mg/prednisone/day for >14 days in the last 30 days)
   3. Oncolytic drug therapy within the past 14 days
   4. Known HIV positive with CD4 count <200 cells/mm3

9. Current treatment with Enbrel® (etanercept), Remicade® (infliximab), Humira® (adalimumab), Cimzia® (certolizumab), or Simponi® (golimumab), Kineret® (anakinra), or Arcalyst® (rilonacept)

10. Pregnancy

11. History of hypersensitivity or idiosyncratic reaction to IC14

12. Deprivation of freedom by administrative or court order

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
IC14	IC14	IC14 4 mg/kg IV on Study Day 1, then IC14 2 mg/kg IV once daily on Study Days 2-4.
Placebo	Placebo	Placebo IV once daily on Study Day 1-4

Primary Outcome Measures

Name	Time	Method
Safety	28 days	The number of toxicities and adverse events that are attributable to treatment. The safety parameters will include an evaluation of the clinical signs and symptoms from the history and physical exam, vital signs, adverse events, and laboratory findings. Immunogenicity studies will measure antibodies against IC14.
Ventilator-free days	28 days	The number of days alive and free of mechanical ventilation through Day 28.

Secondary Outcome Measures

Name	Time	Method
Change in ARDS biologic markers.	28 days	* Change in plasma IL-8, sTNFR1, IL-6 from Day 0 to Day 4; * Change in alveolar neutrophils and total protein from Day 0 to Day 4