Evaluation of the safety and efficacy of Bevacizumab in patients with persistent respiratory disorders after COVID-19 infection

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Decision date (initial)

2025-10-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

French Ministry of Health: ReCH-MIE 2023-2

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To assess efficacy of bevacizumab injection in long COVID patients with impaired DLCO (<75% of predicted value) within 3 months after the first bevacizumab injection. The positive criteria will be a 10% increase in DLCO at three months after the introduction of bevacizumab.

Secondary objectives 5

1. 1- Modification of clinical evaluation at 1, 2, 3 and 7 months and in particular the clinical symptom of dyspnea and fatigue or other related clinical parameters of long-COVID patients.
2. 2- Evaluation at month 3 and month 7 of psychological, cognitive and autonomic functions
3. 3- Modification of other respiratory function markers: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, total lung capacity (TLC), residual volume (RV), and 6 minute walking distance at 1, 2, 3 and 7 months after the initiation of Bevacizumab treatment. Modification of DLCO will also be evaluated at 1 and 2 months.
4. 4- Decrease of circulating biomarkers of angiogenesis disorders or endotheliopathy at 1, 2, 3 and 7 months after the initiation of bevacizumab treatment.
5. 5- Safety of bevacizumab in long-COVID patients during the 7 months of follow-up

Conditions and MedDRA coding

Adult patients with persistent dyspnea more than 3 months after acute COVID-19 infection.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1- Patients over 18 years ≤70 years
2. 2- Social security affiliation
3. 3- Good understanding of the French language
4. 4- Written informed consent
5. 5- Documented COVID-19 infection (PCR or CT scan) more than 3 months before inclusion
6. 6- Long COVID suspicion with dyspnea (mMRC≥2 at inclusion)
7. 7- DLCO<75% of predicted value less than 3 months old on the day of screening or to be obtained before Day 1 if older than 3 months.

Exclusion criteria 24

1. 1- Acute COVID-19 infection
2. 14- Active cancer
3. 15- Known hypersensitivity to bevacizumab or any ingredient in its formulation, including non-medicinal ingredients, or a component of the container
4. 16- Hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanized antibodies.
5. 17- History of Radiotherapy
6. 18- History of bisphosphonates treatment
7. 19- Surgery in 28 days before inclusion
8. 20- Participation in another interventional study or being in the exclusion period at the end of a previous study
9. 21- Patient unable or unwilling to comply with the follow-up schedule (at the investigator's discretion)
10. 22- Pregnant or breastfeeding women
11. 23- Vulnerable populations (patient under guardianship, curatorship, deprived of liberty)
12. 2- Lung scintigraphy and thoracic CT angiography evaluation to rule out pulmonary embolism
13. 24- Patient on AME (state medical aid)
14. 3- Women of childbearing potential
15. 4- Myocardial infarction or stroke
16. 5- Uncontrolled hypertension (>140/90 at inclusion in the study)
17. 6- Proteinuria/creatinuria ratio > 50mg/mmol at baseline
18. 8- History of malignant hypertension
19. 10 - Previous osteonecrosis
20. 11- History of Aneurysms and artery dissections
21. 7- DFG<30 ml/min
22. 9- Diagnosis of other pulmonary diseases known to impair DLCO (such as chronic obstructive pulmonary disease [COPD], idiopathic pulmonary fibrosis, interstitial lung diseases unrelated to COVID-19, or other significant chronic pulmonary conditions)
23. 12- History of hemoptysis of any grade
24. 13- History of congestive heart failure (NYHA class II-IV)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is defined as the rate of patients with 10% increase of impaired DLCO within the 3 months after the introduction of bevacizumab.

Secondary endpoints 5

1. 1- Description of clinical symptoms at 1, 2, 3 and 7 months after the initiation of bevacizumab treatment in particular mMRC Scale, Borg Scale, STOP-BANG Questionnaire, WHODAS 2.0, Epworth Sleepiness Scale, which assess fatigue severity in long-COVID patients.
2. 2- Description of psychological, cognitive, and autonomic functions at 3 and 7 months after the initiation of Bevacizumab treatment. In particular, additional assessments will be conducted to evaluate psychological, cognitive, and autonomic functions with the Nijmegen Questionnaire, the Hospital Anxiety and Depression Scale, the Montreal Cognitive Assessment, the self-reported Ricci-Gagnon Physical Activity Questionnaire, the Somatic Symptom Disorder Scale-12 (SSD-12) an
3. 3- Description of other parameter than DLCO explored by Pulmonary Function Test evaluated at 1, 2, 3 and 7 months after the initiation of Bevacizumab treatment. Difference of FEV1, FVC, FEV1/FVC ratio, TLC, RV and 6 minute walking distance between baseline and 1, 2, 3 and 7 months and the difference of DLCO between baseline and 1and 2 months.
4. 4- Difference of circulating angiogenic biomarkers levels between baseline and 1, 2, 3 and 7 months after the initiation of Bevacizumab treatment.
5. 5- Number of side effects related to bevacizumab and proportion of patients with hospitalization or medical consultation during the 7 months after the start of the treatment.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr David SMADJA

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr David SMADJA

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 23 files

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

Application history

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