Safety and efficacy of anakinra treatment for patients with persistent respiratory symptoms post acute covid and immune system activation: the PRECISION double-blind, randomized clinical trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hellenic Institute For The Study Of Sepsis

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Immune System Diseases [C20]

Trial duration

3 Nov 2023 → ongoing

Decision date (initial)

2024-12-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-508123-12-00

EudraCT number

2023-000102-25

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

PRECISION is a proof-of-concept, phase II/III randomized clinical trial (RCT) aiming to evaluate the efficacy and safety of anakinra in patients with PACS in improving the clinical and immunological state over 4 to 8 weeks as measured by a composite endpoint, namely, the “Score of PACS progression reversal”.

Conditions and MedDRA coding

Post-Acute COVID Syndrome (PACS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age equal to or above 18 years
2. Male or female gender
3. In the case of women of childbearing age and men, an adequate method of contraception should be used during the study.
4. Written informed consent provided by the patient.
5. History of confirmed COVID-19 infection the last 90 days or more
6. 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
7. Parallel presence of two conditions: a) impaired Lung Function tests (defined as: DLCOcor <76% or TLC lower than normal or FVC lower than normal) AND b) radiological findings in high resolution chest tomography compatible with inflammatory-like pattern or mixed inflammatory-fibrotic pattern involving at least 15% of the total lung parenchyma.

Exclusion criteria 16

1. Age below 18 years
2. Denial for written informed consent
3. Any stage IV malignancy
4. Any primary immunodeficiency
5. Less than 1,500 neutrophils/mm3
6. Known hypersensitivity to anakinra
7. Known lung fibrosis prior to COVID-19
8. Medical history of pulmonary hypertension or chronic heart failure
9. Known chronic obstructive pulmonary disease GOLD stage 3 or 4 prior to COVID- 19
10. Known active tuberculosis (under treatment) or latent tuberculosis (by positive tuberculin test)
11. 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.
12. Any anti-cytokine biological treatment the last one month
13. Severe hepatic failure defined as Child-Pugh stage of 3
14. End-stage renal failure necessitating hemofiltration or peritoneal hemodialysis
15. Pregnancy or lactation. Women of child-bearing potential will be screened by a urine pregnancy test before inclusion in the study
16. Participation in any other interventional trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. A positive score is achieved when both of the Conditions A and B are completed. The conditions A and B are explicitly explained in the study protocol.

Secondary endpoints 9

1. 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)
2. Changes in cytokine production capacity of stimulated PBMCs at week 4 between the two arms of treatment
3. Change of each component of the score for the primary outcome at week 4 between the two arms of treatment
4. At least 10% decrease of the pulmonary artery pressure at week 4 between the two arms of treatment
5. At least 10% increase of LV ejection fraction (if abnormal at baseline) at week 4 between the two arms of treatment
6. The number of meters walked during the 6-min walk test between the two arms of treatment at week 4
7. The number of meters walked during the 6-min walk test between patients receiving 8 weeks anakinra treatment compared to patients receiving 4 weeks anakinra treatment
8. Number of criteria of the Condition A met
9. Safety of anakinra

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hellenic Institute For The Study Of Sepsis

Sponsor organisation

Hellenic Institute For The Study Of Sepsis

Address

Michalakopoulou 88

City

Athens

Postcode

115 28

Country

Greece

Scientific contact point

Organisation

Hellenic Institute For The Study Of Sepsis

Contact name

Evangelos Giamarellos-Bourboulis

Public contact point

Organisation

Hellenic Institute For The Study Of Sepsis

Contact name

Evangelos Giamarellos-Bourboulis

Third parties 1

Locations

4 EU/EEA countries · 23 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 30 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications