Page Nct des essais cliniques

Summary
EudraCT Number:2020-003146-36
Sponsor's Protocol Code Number:RIAlta-1
National Competent Authority:Netherlands - Competent Authority
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2022-09-11
Trial results
Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL
A. Protocol Information
A.1Member State ConcernedNetherlands - Competent Authority
A.2EudraCT number2020-003146-36
A.3Full title of the trial
Safety of Rifampicin at High Dose for the Treatment of Adult Subjects with Complex Drug Susceptible Pulmonary and Extrapulmonary Tuberculosis
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Rifampicin at High Dose for Complex Tuberculosis, RIAlta study
A.3.2Name or abbreviated title of the trial where available
RIAlta study
A.4.1Sponsor's protocol code numberRIAlta-1
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorVall d'Hebron Research Institute (VHIR)
B.1.3.4CountrySpain
B.3.1 and B.3.2Status of the sponsorNon-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportEuropean Commission (RISE, Marie Curie Horizon 2020)
B.4.2CountryEuropean Union
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationVall d’Hebron Research Institute
B.5.2Functional name of contact pointComité Étic d'Investigació Clínica
B.5.3 Address:
B.5.3.1Street AddressPasseig de la Vall d’Hebron 119
B.5.3.2Town/ cityBarcelona
B.5.3.3Post code08035
B.5.3.4CountrySpain
B.5.6E-mailceic@vhir.org
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Rifampicin
D.2.1.2Country which granted the Marketing AuthorisationNetherlands
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameRifampicin
D.3.4Pharmaceutical form Tablet
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
Oral use
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Pulmonary and extrapulmonary tuberculosis
E.1.1.1Medical condition in easily understood language
Pulmonary and extrapulmonary tuberculosis
E.1.1.2Therapeutic area Diseases [C] - Bacterial Infections and Mycoses [C01]
MedDRA Classification
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
To evaluate the safety of high-dose rifampicin (35 mg/kg/d) supplemented with standard doses of isoniazid, pyrazinamide, and ethambutol for 8 weeks in adult subjects with pulmonary or extrapulmonary drug susceptible tuberculosis (DS-TB) belonging to difficult to treat subgroups.
E.2.2Secondary objectives of the trial
To evaluate the tolerability (of high-dose rifampicin (35 mg/kg/d) supplemented with standard doses of isoniazid, pyrazinamide, and ethambutol for 8 weeks in adult subjects with pulmonary or extrapulmonary TB belonging to difficult to treat patient subgroups.
To evaluate the efficacy of high dose rifampicin (35 mg/kg) supplemented with standard doses of isoniazid, pyrazinamide, and ethambutol for 8 weeks by assessing early sterilizing activity in the sputum of pulmonary TB subjects belonging to difficult to treat patient subgroups.
E.2.3Trial contains a sub-study Yes
E.2.3.1Full title, date and version of each sub-study and their related objectives
1-To describe pharmacokinetics-pharmacodynamics (PK/PD) of rifampicin at high doses in difficult-to-treat pulmonary and extrapulmonary TB.
2-To describe tuberculosis associated costs and the quality of life of DSTB participants.
E.3Principal inclusion criteria
The participant must fulfill either criteria nr. 1-4 AND nr. 5 OR criteria nr. 1-4 AND 6, AND anyone of 7-14:
1. Subjects with confirmed or probable pulmonary or extra pulmonary DS-TB.
2. Informed consent provided.
3. Positive smear, positive Xpert MTB/RIF test, positive M. tuberculosis culture (confirmed cases) OR histological study compatible with necrotizing granulomas OR a liquid biochemistry (pleural, pericardial, ascites or cerebrospinal fluid) suggestive of TB together with clinical symptoms resembling TB disease in the absence of any other possible cause (probable cases).
4. Female participants of childbearing age must have a negative pregnancy test at baseline.
AND
5. Age ≥ 60 years old.
OR
6. Age ≥ 18 years
AND one of the following
7. Body mass index ≤ 18.5
8. Human Immunodeficiency Virus (HIV) infection.
9. Diabetes Mellitus
10. Hepatitis C virus (HCV) infection (positive HCV serology)
11. Hepatitis B virus (HBV) infection (positive HBV surface antigen)
12. Daily alcohol intake ≥ 2 units of alcohol (1 unit of alcohol: 4% alcohol 250ml (ie beer); 4.5% alcohol 218ml (i.e. cider); 13% alcohol 76ml (i.e. wine); 40% alcohol 25ml (i.e. whisky))
13. Chronic liver disease of any other cause (metabolic, toxic, autoimmune)
14. Central Nervous System TB involvement
E.4Principal exclusion criteria
Subjects will be excluded from entry if ANY ONE of the criteria listed below is met:
1. Rifampicin resistance confirmation.
2. Barthel index <40 for subjects older than 60 years old.
3. Signs of liver disease not related to TB [Liver enzymes (AST or ALT) > 5x upper limit of normal , Total bilirubin > 5x upper limit of normal, Patients with a Child-Pugh grade C cirrhosis or acute decompensation of their chronic liver disease at enrolment.]
4. Subjects with known allergy or sensitivity to rifampicin, or any of the other components of DS-TB treatment.
5. Treatment with any of the following: rifampicin, isoniazid, pyrazinamide, ethambutol, levofloxacin, or moxifloxacin within the last month for at least 14 days or current TB treatment for more than 7 days.
6. The subject is enrolled in any other investigational trial that includes a drug intervention.
7. Subjects with solid organ transplantation or bone marrow transplantation.
8. Subjects with an active onco-hematological neoplasm.
9. Previous severe pulmonary disease, other than pulmonary DS-TB, according to local investigator.
10. Pre-existing epilepsy or psychiatric disorder according to local investigator.
11. Ischemic heart disease OR severe arrhythmia within 6 months OR Atrial Fibrillation with oral anticoagulant therapy indication when transitioning to low-molecular weight heparin is not feasible.
12. Positive pregnancy test
13. Breastfeeding women.
14. The subject used any drugs or substances known to be strong inhibitors or inducers of cytochrome P450 enzymes which are involved in the degradation pathways of rifampicin within the time windows specified in the protocol.
E.5 End points
E.5.1Primary end point(s)
Proportion of participants experiencing severe adverse events (grade 3 or superior according to the Common Terminology Criteria for Adverse Events, CTCAE version 5) compared to historical controls on 10mg/kg/day of rifampicin.
E.5.1.1Timepoint(s) of evaluation of this end point
8 weeks.
E.5.2Secondary end point(s)
1-Proportion of all adverse events (grade 1-4) including treatment dropout rates.
2- Association of high dose rifampicin with the culture conversion in liquid media at 8 weeks.
E.5.2.1Timepoint(s) of evaluation of this end point
8 weeks.
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic Yes
E.6.7Pharmacodynamic Yes
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic Yes
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) Yes
E.7.3Therapeutic confirmatory (Phase III) No
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised No
E.8.1.2Open Yes
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group No
E.8.1.6Cross over No
E.8.1.7Other Yes
E.8.1.7.1Other trial design description
Historical control
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo No
E.8.2.3Other Yes
E.8.2.3.1Comparator description
Standard doses of rifampicin
E.8.2.4Number of treatment arms in the trial1
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned4
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA4
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA Yes
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
Paraguay
E.8.7Trial has a data monitoring committee No
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
The last 8-week visit of the last participant undergoing the trial.
As TB treatment must continue up to 26 weeks according to WHO guidelines, and there is a high risk of relapse up to 1 year after treatment end, it is usual practice to follow-up TB patients up to 1 year after treatment end (at the same sites involved in the study which are health care public providers). An extended follow up will be offered to participants.
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years1
E.8.9.1In the Member State concerned months6
E.8.9.1In the Member State concerned days
E.8.9.2In all countries concerned by the trial years1
E.8.9.2In all countries concerned by the trial months6
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 30
F.1.3Elderly (>=65 years) Yes
F.1.3.1Number of subjects for this age range: 10
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation Yes
F.3.3.6Subjects incapable of giving consent personally Yes
F.3.3.6.1Details of subjects incapable of giving consent
Critically il TB patients (for example, but not limited to: TB meningitis and severe lung TB)
F.3.3.7Others Yes
F.3.3.7.1Details of other specific vulnerable populations
Low body weight, diabetic, HIV, Hepatitis B and C, alcoholic and chronic liver disease patients.
F.4 Planned number of subjects to be included
F.4.1In the member state40
F.4.2 For a multinational trial
F.4.2.1In the EEA 114
F.4.2.2In the whole clinical trial 134
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
None different from the expected notmal treatment.
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2023-11-15
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2022-09-07
P. End of Trial
P.End of Trial StatusOngoing

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