Evaluation of the Early Bactericidal Activity of Tedizolid and Linezolide Against Mycobacterium Tuberculosis (TEDITUB)

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] - Bacterial Infections and Mycoses [C01]

Trial duration

20 Apr 2023 → ongoing

Decision date (initial)

2024-08-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512759-19-00

EudraCT number

2022-000630-42

ClinicalTrials.gov

NCT05534750

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

Assessment of the early bactericidal activity (EBA) of tedizolid (200mg / day) at the end of the first 2 days of treatment (D3).

Secondary objectives 5

1. Evaluation of the early bactericidal activity (EBA) of tedizolid between Day 3 and Day 8
2. Comparison of the early bactericidal activity (EBA) of tedizolid and linezolide between Day 1 and Day 3 and between Day 3 and Day 8
3. Comparison of the early bactericidal activity (EBA) of tedizolid and quadruple therapy between Day 1 and Day 3 and between Day 3 and Day 8
4. Tedizolid pharmacokinetics'measurement
5. Evaluation of Tedizolid's tolerance

Conditions and MedDRA coding

first suspected infection with Mycobacterium tuberculosis in the lungs

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age ≥ 18 years old and <75 years old
2. Woman on childbearing age should be on effective contraception during the duration of the study and up to 6 months after treatment; a mechanical contraception (use of condom) will be strongly recommended
3. Male (effective contraception must be used during duration of the study and up to 3 months after treatment)
4. Patient with a first infection with Mycobacterium tuberculosis of pulmonary localization suspected by the presence of a clinical pulmonary symptomatology, a chest X-ray or an abnormal chest computed tomography, and the positive microscopic examination of a sputum (AFB +, presence of AFB) with confirmation of tuberculosis by a genotypic test demonstrating no resistance to rifampicin, without clinical signs of extra-thoracic involvement
5. State medical assistance application being processed ( If patient does not benefit from social security),
6. Signature of informed consent

Exclusion criteria 18

1. Resistance to one of the anti-tuberculosis drugs used detected by a genotypic test in accordance with the recommendations of the High Council of Public Health of 2015;
2. History of anti-tuberculosis treatment;
3. History of treatment in the previous two years with one of the antibiotics evaluated in this trial lasting more than one month;
4. Absolute contraindication to the use of at least one of the test molecules (isoniazid, rifampicin, ethambutol, pyrazinamide, linezolid, tedizolid);
5. Tuberculosis having, in the opinion of the investigator, severity criteria not allowing to wait 7 days before starting standard treatment (oxygenorequirement, severe immunosuppression, extra-pulmonary involvement, any sign of severity requiring treatment in intensive care unit);
6. HIV-infected patient receiving protease inhibitors whose antiviral treatment cannot be changed and therefore cannot receive rifampicin; or any other drug contraindicated with one of the study treatments (the list of contraindicated drugs is detailed in the following non-inclusion criteria).
7. Neoplastic pathology during treatment with chemo and / or radiotherapy;
8. Decompensated cirrhosis;
9. Pregnancy, desire to become pregnant, breast-feeding (for women of childbearing potential, contraception should be used for the duration of the study and up to 6 months after treatment, mechanical contraception will be strongly recommended and up to 3 months after treatment);
10. Protected adults (under guardianship, curatorship) and under safeguard of justice
11. Significant laboratory abnormalities (hemoglobin <9g / dl, polynuclear neutrophils <500 / mm3, platelets <50,000 / mm3, creatinine clearance <30ml / min, ASAT or ALAT> 3N, and total bilirubin> 3N)
12. Hyperuricaemia
13. Porphyria
14. Optic neuritis or peripheral neuropathy
15. BMI≤ 16 kg/m2
16. Participation in other interventional research
17. Current treatment with one or more medications contraindicated in combination with linezolid: Linezolid should not be used in patients treated with monoamine oxidase A or B inhibitors (for example: phenelzine, isocarboxacid, selegiline, moclobemide) or who received one of these products in the previous two weeks
18. Combination with bictegravir, cobicistat, daclatasvir, dasabuvir, delamanid, grazoprevir/elbasvir, protease inhibitors boosted by ritonavir, isavuconazole, ledipasvir, lurasidone, midostaurin, ombitasvir/paritaprevir, praziquantel, rilpivirine, sofosbuvir, velpatasvir, voriconazole, voxilaprevir Gastrointestinal topicals, antacids and adsorbents and salts and aluminum hydroxides

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The measurement will be done as follow: EABD1D3= (log10 number of CFU (CFU= colony forming unit) of M. tuberculosis on medium 7H11/mL of sputum on D1) - (log10number of CFU of M. tuberculosis on medium 7H11/mL of sputum on D3)/2.

Secondary endpoints 9

1. The measurement will be done as follow: EBAD3D8= (log10 number of CFU (CFU=colony forming unit) of M. tuberculosis on medium 7H11/mL of sputum on D3) - ( log10 number of CFU of M. tuberculosis on medium 7H11/mL of sputum at D8)/5
2. Compare the early bactericidal activity of tedizolid 200 mg / day to that of linezolid 1200 mg / day between Day 1 and Day 3 and between Day 3 and Day 8
3. Compare the early bactericidal activity of tedizolid 200 mg / day to that of standard quadruple therapy between Day 1 and Day 3 and between Day 3 and Day 8
4. ABPJ1J3 of tedizolide measured in terms of time to positivity of cultures in liquid medium called ABPJ1J3L= (time to positivity of culture of sample at D3) - (time to positivity of culture of sample at D1)/2 (i.e. after the first 2 days of treatment with tedizolide)
5. Bactericidal activity in liquid medium between D3 and D8 (ABPJ3J8L) of tédizolide
6. ABPJ1J3L and ABPJ3J8L of tedizolide compared with linezolide
7. ABPJ1J3L and ABPJ3J8L of tedizolide compared with standard four-therapy treatment
8. Total and free concentration of tedizolid measured at 0, 1, 3, 5, and 24h, Area under the curve (AUC)
9. Toxicity of tedizolide assessed at D7 and D30. Adverse events leading to premature discontinuation of treatment

Investigational products

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

Test 2

Comparator 5

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 Nicolas VEZIRIS

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Nicolas VEZIRIS

Locations

1 EU/EEA country · 7 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 19 files

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

Application history

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