Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock (ASTONISH)

• ClinicalTrials.gov Identifier: NCT04055909
• Recruitment Status: Recruiting
• First Posted: August 14, 2019
• Last Update Posted: February 28, 2020
• Sponsor: Inotrem
• Information provided by (Responsible Party): Inotrem

Study Description

Brief Summary:

This is a randomized, double-blind, placebo-controlled dose-selection study in which two doses of nangibotide are tested versus placebo.

All patients with a diagnosis of septic shock will be considered for study participation. All potential study patients will receive standard of care for the treatment of septic shock.

After screening for eligibility, patients meeting all inclusion and no exclusion criterion will be randomized. Patients will be randomized to one of three treatment arms.

Treatment with study drug must be initiated as early as possible, but no later than 24 hours after the onset of septic shock, defined by the start of vasopressor therapy.

Patients will be treated for at least 3 days with study drug. After the first 3 days of treatment, patients still requiring vasopressor will be treated until 24 hours after vasopressor withdrawal with a maximum treatment duration of 5 days.

Patients will be assessed at the End of Study (EoS) visit at day 28. After the last patient's day 28 visit, the study will be analyzed. Additional follow up (FU) visits will be conducted after 90 days, 6 and 12 months.

The objective of the study ist to compare the safety, tolerability and efficacy of two doses of nangibotide versus placebo, when given in addition to standard of care.

Condition or disease	Intervention/treatment	Phase
Shock, Septic	Drug: nangibotide low dose; Drug: nangibotide high dose; Drug: placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 450 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock. A Randomized, Double-blind, Placebo Controlled Dose Selection Study
• Actual Study Start Date: November 13, 2019
• Estimated Primary Completion Date: April 2021
• Estimated Study Completion Date: March 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: nangibotide 1	Drug: nangibotide low dose; nangibotide 0.3 mg/kg/h
Experimental: nangibotide 2	Drug: nangibotide high dose; nangibotide 1.0 mg/kg/h
Placebo Comparator: Placebo	Drug: placebo; matching placebo

Outcome Measures

Primary Outcome Measures :

1. Sequential organ failure assessment (SOFA) score [ Time Frame: day 5 ]
   Change of total SOFA score from baseline to day 5 (in the subgroup defined by patients with elevated sTREM-1 baseline levels and in the overall population)

Secondary Outcome Measures :

1. All-cause mortality [ Time Frame: day 28 ]
   Survival and all-cause mortality on D28

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Provide written informed consent
2. Age 18 to 85 years (inclusive)
3. Documented or suspected infection: lung, abdominal or urinary tract infection (UTI) in the elderly (≥65 years)
4. Organ dysfunction defined as acute change in total SOFA score ≥ 2 points
5. Refractory hypotension requiring vasopressors to maintain MAP ≥65mm Hg despite adequate volume resuscitation
6. Hyperlactatemia (blood lactate >2 mmol/L or 18 mg/dL).

Exclusion Criteria:

1. Previous episode of septic shock requiring vasopressor administration within current hospital stay
2. Underlying concurrent immunodepression with anti-CD52 alemtuzumab (Campath) or glucocorticoids >75 mg prednisone daily or equivalent for more than 7 days
3. Immunosuppressive therapy related to recent (<6 months) transplantation
4. Cancer chemotherapy (<3 months) implying an immunodepression
5. Known HIV infection with low CD4 cell count (<200) for at least 6 months
6. Known pregnancy (positive urine or serum pregnancy test)
7. Shock of any other cause, e.g. hypotension related to gastrointestinal bleeding
8. Ongoing documented or suspected endocarditis
9. End-stage neurological disease
10. End-stage cirrhosis (Child Pugh Class C)
11. Acute Physiology and Chronic Health Evaluation (APACHE II) score <15 or ≥ 34
12. Home oxygen therapy on a regular basis for > 6 h/day
13. Recent cardiopulmonary resuscitation (CPR) (within current hospital stay)
14. Body mass index (BMI) ≥ 40 kg/m2or weight ≥ 130 kg
15. Moribund patients
16. Decision to limit full care taken before obtaining informed consent
17. Participation in another interventional study in the 3 months prior to randomization

Contacts and Locations

Contacts

Contact: Jean-Jacques Garaud, MD; +33 (0)9 66 81 79 00; astonish@inotrem.com

Locations

Belgium

Cliniques Universitaires Saint-Luc; Recruiting

Bruxelles, Belgium

Contact: Pierre-Francois Laterre, MD

France

Hôpital Universitaire Dupuytren; Recruiting

Limoges, France

Contact: Bruno Francois, MD

Spain

Hospital Universitario Vall d'Hebrón; Recruiting

Barcelona, Spain

Contact: Ricardo Ferrer, MD

Sponsors and Collaborators

Inotrem

Investigators

• Study Director: Jean-Jacques Garaud, MD; CEO and Medical Officer

More Information

• Responsible Party: Inotrem
• ClinicalTrials.gov Identifier: NCT04055909
• Other Study ID Numbers: MOT-C-203; 2018-004827-36 ( EudraCT Number )
• First Posted: August 14, 2019
• Last Update Posted: February 28, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Inotrem:

Septic Shock

Additional relevant MeSH terms:

Shock, Septic; Shock; Pathologic Processes; Sepsis; Infection; Systemic Inflammatory Response Syndrome; Inflammation