Safety and Efficacy of Anakinra Treatment for Patients With Post Acute Covid Syndrome

NCT05926505 | Recruiting Phase 2

• 2 other identifiers: PRECISION2023-000102-25
• Study Type: interventional
• Target: 182
• Locations: 4 countries
• Sites: 24

Brief Summary

The PRECISION is a proof-of-concept, phase II randomized clinical trial aiming to evaluate the efficacy and safety of anakinra in patients with Post-Acute COVID Syndrome (PACS) of the pro-inflammatory respiratory phenotype. Improvement is measured by a composite endpoint, namely, the "Score of PACS progression reversal"

Conditions

Post-Acute COVID-19 Syndrome; Post-Acute COVID-19; Long COVID

Keywords

COVID-19; Long COVID; Post-Acute COVID-19; Anakinra; PRECISION; NCT05926505

Outcome Measures

Primary Outcomes (1)

• Score of PACS progression reversal

  A positive score is defined differently for patients enrolled in the study because of Condition 1 or Condition 2. For patients enrolled in Condition 1, a positive score comprises at least two of the following: 1. At least 20% improvement of restrictive lung disease from baseline 2.No need for hospitalization οr admission to the Emergency Department 3. No increase of the degree of lung fibrosis score in lung HRCT For patients enrolled in Condition 2, a positive score comprises at least two of the following: 1. At least 20% decrease of the total score in lung HRCT OR Improved exercise capacity in the 6min walk test. 2.No need for hospitalization οr admission to the Emergency Department. 3.No increase of the degree of lung fibrosis score in lung HRCT. The proportion of patients achieving the above composite endpoint compared to placebo at week 4 will be the primary study endpoint.

  Through study completion,an average of 2 years

Secondary Outcomes (5)

• The frequency of the Score of PACS progression reversal between patients receiving 8 weeks anakinra treatment compared to patients receiving 4 weeks anakinra treatment (+4 weeks of placebo).

  Through study completion,an average of 2 years

• Changes of concentration of cytokines produced by stimulated PBMCs at week 4 between the two arms of treatment.

  Through study completion,an average of 2 years

• Change of each component of the score for the primary outcome at week 4 between the two arms of treatment.

  Through study completion,an average of 2 years

• At least 10% decrease of the pulmonary artery pressure at week 4 between the two arms of treatment.

  Through study completion,an average of 2 years

• At least 10% increase of LV ejection fraction (if abnormal at baseline) at week 4 between the two arms of treatment.

  Through study completion,an average of 2 years

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo is injected subcutaneously once daily for 4 weeks.

Drug: Placebo

Anakinra

EXPERIMENTAL

Anakinra is injected subcutaneously as 100 mg once daily for 4 weeks.

Drug: Anakinra 149 MG/ML Prefilled Syringe [Kineret]

Interventions

Placebo DRUG

Placebo is injected subcutaneously once daily for 4 weeks. After the period of 4 weeks, patients allocated to arm 1 will be shifted to subcutaneous treatment with 100mg anakinra once daily for 4 weeks.

Placebo

Anakinra 149 MG/ML Prefilled Syringe [Kineret] DRUG

Anakinra is injected subcutaneously as 100 mg once daily for 4 weeks. After the first period the patients will be randomized 1:1 to continue receiving subcutaneous treatment with 100mg anakinra once daily for 4 weeks or placebo once daily for 4 weeks.

Anakinra

Eligibility Criteria

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

You may qualify if:

• Age equal to or above 18 years
• Male or female gender
• In the case of women of childbearing age and men, an adequate method of contraception should be used during the study. Contraception should be maintained for at least a period of 3 months after the discontinuation of treatment. As an adequate method of contraception, it is suggested: -male or female condom with or without spermicide -contraceptive cap, a diaphragm or contraceptive sponge with a spermicide Prior to admission to the study, a pregnancy test will be performed to exclude pregnancy to women of childbearing age.
• Written informed consent provided by the patient. For subjects without decision-making capacity, informed consent must be obtained from a legally designated representative following the national legislation in the Member State where the trial is planned.
• History of confirmed COVID-19 infection the last 90 days or more
• Symptoms compatible with PACS (defined as at least one positive answer to the questionnaire for restriction of daily activities) lasting for more than 2 months
• Serum levels of IP-10 more than 250 pg/ml
• Presence of ONE of the following two clinical conditions: Condition 1: Impaired Lung Function tests (defined as: DLCOcor \<76% AND TLC and/or FVC lower than 80% of predicted) Condition 2: At least a total radiology score in HRCT more than 20 OR walking of a distance less than 500m in the 6-minute walk test
• If patients meet the criteria for both Conditions 1 and 2, they will be considered for randomization and evaluation for the primary endpoint as in Condition 1.

You may not qualify if:

• Age below 18 years
• Denial for written informed consent
• Any stage IV malignancy
• Any primary immunodeficiency
• Less than 1,500 neutrophils/mm3
• Known hypersensitivity to anakinra
• Known lung fibrosis prior to COVID-19
• Medical history of pulmonary hypertension or chronic heart failure
• Known chronic obstructive pulmonary disease GOLD stage 3 or 4 prior to COVID-19
• Known active tuberculosis (under treatment) or latent tuberculosis (by positive tuberculin test)
• Oral or IV intake of corticosteroids at a daily dose equal or greater than 0.4 mg/kg prednisone for a period greater than the last 15 days.
• Any anti-cytokine biological treatment the last one month
• Severe hepatic failure defined as Child-Pugh stage of 3
• End-stage renal failure necessitating hemofiltration or peritoneal hemodialysis
• Participation in any other interventional trial

Sponsors & Collaborators

• Hellenic Institute for the Study of Sepsis: lead

Study Sites (24)

Out-patient long-COVID department, Jena University Hospital

Jena, Germany

NOT YET RECRUITING

Out-patient long-COVID department, Patras University General Hospital

Pátrai, Achaia, 26504, Greece

RECRUITING

Out-patient long-COVID department III, Evangelismos Athens General Hospital

Athens, Attica, 10676, Greece

NOT YET RECRUITING

Out-patient long-COVID department I, Sotiria Athens Hospital of Chest Diseases

Athens, Attica, 11527, Greece

RECRUITING

Out-patient long-COVID department II, Sotiria Athens Hospital of Chest Diseases

Athens, Attica, 11527, Greece

RECRUITING

Out-patient long-COVID department IV, Sotiria Athens Hospital of Chest Diseases

Athens, Attica, 11527, Greece

RECRUITING

Out-patient long-COVID department, Laiko General Hospital

Athens, Attica, 11527, Greece

RECRUITING

2nd Department of Propedeutic Medicine, ATTIKON University General Hospital

Chaïdári, Attica, 12462, Greece

RECRUITING

4th Department of Internal Medicine, ATTIKON University General Hospital

Chaïdári, Attica, 12462, Greece

RECRUITING

Out-patient long-COVID department, Ioannina University General Hospital

Ioannina, Ioannina, 455 00, Greece

RECRUITING

Out-patient long-COVID department, Tzaneion Piraeus General Hospital

Piraeus, Piraeus, 18536, Greece

RECRUITING

Out-patient long-COVID department, Alexandroupolis University General Hospital

Alexandroupoli, 68100, Greece

RECRUITING

Out-patient long-COVID department X, Sotiria Athens Hospital of Chest Diseases

Athens, 115 27, Greece

RECRUITING

Out-patient long-COVID department, University Hospital of Larissa

Larissa, 41110, Greece

NOT YET RECRUITING

Out-patient long-COVID department II, Thriasio General Hospital of Elefsina

Magoula, 196 00, Greece

RECRUITING

Out-patient long-COVID department I, Thriasio General Hospital of Elefsina

Magoula, 19600, Greece

RECRUITING

Out-patient long-COVID department, AHEPA Hospital of Thessaloniki

Thessaloniki, 54636, Greece

RECRUITING

Infectious Diseases Clinic, Ospedale Policlinico San Martino IRCCS and Department of Health Sciences, University of Genova, Genoa, Italy

Genova, Italy

NOT YET RECRUITING

Department of Internal Medicine, Hospital of Jesolo, Italy

Jesolo, Italy

NOT YET RECRUITING

Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS Ospedale San Raffaele & Vita-Salute San Raffaele University, Milan, Italy

Milan, Italy

NOT YET RECRUITING

Infectious Diseases Clinic, University of Modena, Italy

Modena, Italy

NOT YET RECRUITING

Dipartimento Scienze di Laboratorio e Infettivologiche - Fondazione Policlinico Gemelli IRCCS, Roma Italy

Rome, Italy

NOT YET RECRUITING

ID Respiratory Unit, Spallanzani Institute of Rome, Italy

Rome, Italy

NOT YET RECRUITING

Department of Pulmonary Medicine, Barcelona University Hospital

Barcelona, Spain

NOT YET RECRUITING

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; COVID-19

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Evangelos Giamarelos-Bourboulis, MD,PhD

  Hellenic Institute for the Study of Sepsis

  STUDY CHAIR

Central Study Contacts

Evangelos Giamarelos-Bourboulis, MD,PhD

CONTACT

00302105831994; egiamarel@med.uoa.gr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2023
• First Posted: July 3, 2023
• Study Start: September 6, 2023
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: January 8, 2026

Record last verified: 2026-01

Locations

IT (6); DE (1); GR (16); ES (1)