Efficacy and Safety of Emapalumab and Anakinra in Reducing Hyperinflammation and Respiratory Distress in Patients With COVID-19 Infection.

NCT04324021 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: Sobi.IMMUNO-1012020-001167-93
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 12

Brief Summary

Hyper-inflammation, caused by a cytokine storm resulting from an exaggerated response of the immune system in the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is considered to represent one of the most important negative prognostic factors in patients infected with sSARS-CoV-2. The objective of this study is to investigate new treatment options to reduce the number of patients requiring mechanical ventilation. This is intended to address the most urgent need to preserve the access to intensive care unit support to the lowest possible number of patients and may potentially reduce mortality.

Conditions

SARS-CoV-2

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment Success

  Defined as the number of patients not requiring invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO)

  Up to Day 15

Secondary Outcomes (31)

• Number of Participants Requiring Mechanical Ventilation

  Date of randomization to date of mechanical ventilation, up to 15 Days

• Change From Baseline in Modified Early Warning System Score

  Baseline, Day 15

• Change From Baseline in Ferritin

  Baseline, Days 4, 7, 10, 13 and 15

• Change From Baseline in Lactate Dehydrogenase (LDH)

  Baseline, Days 4, 7, 10, 13 and 15

• Change From Baseline in D-dimers

  Baseline, Days 4, 7, 10, 13 and 15

Study Arms (3)

Emapalumab

ACTIVE COMPARATOR

Emapalumab i.v. infusion every 3rd day for a total 5 infusions. Day 1: 6mg/kg. Days 4, 7, 10 and 13: 3 mg/kg

Biological: Emapalumab

Anakinra

ACTIVE COMPARATOR

Anakinra i.v. infusion four times daily for 15 days. 400 mg/day in total, divided into 4 doses given every 6 hours

Biological: Anakinra

Standard of care

NO INTERVENTION

Standard of care according to local practice

Interventions

Emapalumab BIOLOGICAL

I.v. infusion every third day

Also known as: Gamifant

Emapalumab

Anakinra BIOLOGICAL

Daily i.v. infusion

Also known as: Kineret

Anakinra

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent provided by the patient, or by the patient's legally authorized representative(s), as applicable.
• Documented presence of SARS-CoV-2 infection as per hospital routine.
• Age \> 18 to \< 85 years at the time of screening.
• Presence of respiratory distress, defined as:
• PaO2/FiO2 \< 300 mm Hg and \>200 mm Hg or
• Respiratory Rate (RR) ≥30 breaths/min or
• Presence of hyperinflammation defined as:
• Lymphocyte counts:
• \< 1000 cells/µL, in patients who have not received systemic glucocorticoids for at least 2 days prior to the assessment of the lymphocyte count
• \< 1200 cells/µL, in patients who have received systemic glucocorticoids for at least 2 days prior to the assessment of the lymphocyte count
• and
• One of the following three criteria:
• i. Ferritin \> 500ng/mL
• ii. LDH \> 300 U/L
• iii. D-Dimers \> 1000 ng/mL

You may not qualify if:

• Patients in mechanical ventilation or with modified early warning score (MEWS) \>4 with evidence of moderate or above ARDS (Berlin definition, namely with PaO2/FiO2 \>100, but \<200 mm Hg) or severe respiratory insufficiency or evidence of rapid worsening (respiratory distress requiring mechanical ventilation or presence of shock or presence of concomitant organ failure requiring ICU admission). Note: For the evaluation of patient eligibility, temperature will not be considered in the calculation of the total MEWS score since presence of fever is a hallmark of SARS-CoV-2 infection
• Impairment of cardiac function defined as poorly controlled heart diseases, such as New York heart association (NYHA) class II (mild) and above, cardiac insufficiency, unstable angina pectoris, myocardial infarction within 1 year before enrollment, supraventricular or ventricular arrhythmia need treatment or intervention.
• Severe renal dysfunction (estimated glomerular filtration rate ≤ 30 mL/min/1.73 m2) or receive continuous renal replacement therapy, hemodialysis, or peritoneal dialysis.
• Uncontrolled hypertension (seated systolic blood pressure \>180 mmHg, or diastolic blood pressure \>110mmHg) .
• Administration of plasma from convalescent patients who recovered from SARS-CoV-2 infection.
• Clinical suspicion of latent tuberculosis.
• History of hypersensitivity or allergy to any component of the study drug.
• Pregnant women.
• Foreseeable inability to cooperate with given instructions or study procedures.
• Clinical suspicion of active mycobacteria, histoplasma capsulatum, herpes zoster, salmonella, and shigella Infections.
• Patients with liver dysfunction defined as AST or ALT \> 5 × ULN

Sponsors & Collaborators

• Swedish Orphan Biovitrum: lead

Study Sites (12)

Regions hospital

Saint Paul, Minnesota, 55101, United States

Location

The Valley hospital

Ridgewood, New Jersey, 07450, United States

Location

NewYork-Presbyterian Queens

Flushing, New York, 11355, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

University of Utah Health

Salt Lake City, Utah, 84108, United States

Location

ASST Spedali Civili di Brescia Dipartimento di Reumatologia e Immunologia Clinica

Brescia, Italy

Location

S.C. Malattie Infettive, Ospedale Galliera

Genova, Italy

Location

Ospedale Maggiore Policlinico, Dipartimento di Anestesia-Rianimazione e Medicina di Urgenza

Milan, Italy

Location

Dipartimento di Medicina - DIMED, Azienda Ospedale - Università Padova

Padua, Italy

Location

Azienda Ospedaliero-Universitaria di Parma, Dipartimento di Malattie infettive ed epatologia

Parma, Italy

Location

Ospedale Lazzaro Spallanzani, Dipartimento di Malattie Infettive ad alta Intensità di cura ed altamente contagiose,Ospedale Lazzaro Spallanzani

Roma, Italy

Location

ASL Città di Torino, Unit of Infectious Diseases, Medicine, Rheumatology

Torino, Italy

Location

Related Publications (1)

• Brands X, de Vries FMC, Uhel F, Haak BW, Peters-Sengers H, Schuurman AR, van Engelen TSR, Lutter R, Cremer OL, Bonten MJ, Schultz MJ, Scicluna BP, van der Poll T; MARS Consortium. Plasma Ferritin as Marker of Macrophage Activation-Like Syndrome in Critically Ill Patients With Community-Acquired Pneumonia. Crit Care Med. 2021 Nov 1;49(11):1901-1911. doi: 10.1097/CCM.0000000000005072.

  PMID: 33935163 DERIVED

MeSH Terms

Interventions

Emapalumab; Interleukin 1 Receptor Antagonist Protein

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Henrick Andersson, Director of Statistical Science
• Organization: Swedish Orphan Biovitrum

henrik.andersson@sobi.com

+46760011816

Study Officials

• Emanuele Nicastri, MD

  Direttore Dipartimento di Malattie Infettive

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2020
• First Posted: March 27, 2020
• Study Start: April 2, 2020
• Primary Completion: November 13, 2020
• Study Completion: November 13, 2020
• Last Updated: March 10, 2022
• Results First Posted: March 10, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (7); US (5)