DATA SHEET OF CLINICAL TRIAL C.T. No 070-15

CLINICAL TRIAL REGISTRATION (EC)

I. SPONSOR INFORMATION

Foreign National

2. LEGAL PERSON 2.1 FOREIGN SPONSOR División de SIDA de los Institutos División de SIDA de los Institutos Registered Name: Registered Tradename: Nacionales de Salud (USA) Nacionales de Salud (USA) FOREIGN SPONSOR REPRESENTATIVE IN PERU

SUBSIDIARY: BRANCH: CRO: OTHER: ______Tradename: - TYPE OF INSTITUTION Instituto Nacional de Salud

II. CLINICAL TRIAL GENERAL INFORMATION

1. CLINICAL TRIAL IDENTIFICATION Scientific Title: RIFAPENTINE-CONTAINING TREATMENT SHORTENING REGIMENS FOR PULMONARY TUBERCULOSIS: A RANDOMIZED, OPEN-LABEL, CONTROLLED PHASE 3 CLINICAL TRIAL Public Title: RIFAPENTINE-CONTAINING TUBERCULOSIS TREATMENT SHORTENING REGIMENS Secundary ID(s): WHO UTN: PER-070-15 Protocol Code: TBTC S31/A5349 Clinicaltrials.gov: NA EUDRACT N°: NA

1 1-2 2 2-3 Study clinical phase: 3 4 Clinical Trial Total Duration: 60 months No Aplica 0(exploratory trials) Enrolment start date in Peru (Initial) 01/01/1900 Worldwide enrolment start date (dd/ (dd/mm/aaaa): 04/01/2016 mm/aaaa): Enrolment start date in Peru (Posterior) (dd/mm/aaaa):

Without starting enrollment In enrollment Peru enrolment status : Enrollment stopped Enrollment closed Other 2. CLINICAL TRIAL GOALS AND DESIGN

Randomnized Simple Non randomnized Double Assignation method Type of blinding No aplica Triple Open

Single arm Parallel Crossed Factorial Assignation Others: ______Study Design This will be an international, multicenter, randomized, controlled, open-label, 3-arm, phase 3 non-inferiority trial. Purpose • To evaluate the efficacy of a rifapentine-containing regimen to determine whether the single substitution of rifapentine for rifampin makes it possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis • To evaluate the efficacy of a rifapentine-containing regimen that in addition substitutes moxifloxacin for ethambutol and continues moxifloxacin during the continuation phase to determine whether it is possible to reduce to seventeen weeks the duration of treatment for drug-susceptible pulmonary tuberculosis 3. STUDY INTERVENTION

Página 1 de 4 Indicate if the product is being developed as: Pharmaceutical product Medical device Herbal product Type of research product Galenic product Complementary product Dietary product and sweetener Other: ______Research product identification N° Product name Generic name Product type ATC 1 Rifaren 300 Rifampicina Producto en investigación de origen J04 - Drogas antimicobacterinas químico 2 MOXIFLOXACINA MOXIFLOXACINA Medicamento J01 - Antibacterianos de uso sistémico 3 ISONIAZIDA ISONIAZIDA Medicamento J - ANTIINFECCIOSOS EN GENERAL PARA USO SISTÉMICO 4 RIFAPENTINA RIFAPENTINA Medicamento J - ANTIINFECCIOSOS EN GENERAL PARA USO SISTÉMICO 5 Ethambutol Tablets BP Etambutol Producto en investigación de origen J04 - Drogas antimicobacterinas químico 6 Pirazinamide Tablets Pirazinamida Producto en investigación de origen J04 - Drogas antimicobacterinas químico

N° Comparator name Generic name Product type ATC Intervention(s) description: N° of Group Name Type of group Intervention(s) description participants

Subjects' treatment time 18 months Subjects' follow up time 18 months 4. Study Population Inclusion Criteria: 1. Individuals must meet all of the following inclusion criteria in order to participate in this study: A. Suspected pulmonary tuberculosis plus one or both of the following: a) at least one sputum specimen positive for acid-fast bacilli on smear microscopy OR b) at least one sputum specimen positive for M. tuberculosis by Xpert MTB/RIF testing, with semiquantitative result of ‘medium’ or ‘high’ and rifamycin resistance not detected. B. Age twelve (12) years or older C. A verifiable address or residence location that is readily accessible for visiting, and willingness to inform the study team of any change of address during the treatment and follow-up period. D. Women of child-bearing potential who are not surgically sterilized must agree to practice an adequate method of contraception (barrier method or non-hormonal intrauterine device) or abstain from heterosexual intercourse during study drug treatment. E. Documentation of HIV infection status. F. For HIV-positive individuals, CD4 T cell count greater than or equal to 100 cells/mm3 based on testing performed at or within 30 days prior to study entry. HIV-positive individuals will be enrolled in a staged approach as described in Section 8.3.10.1, specifically: • Group 1 (“EFV1”): receipt of efavirenz-based antiretroviral therapy (ART) for a minimum of 30 days at the time of enrollment AND a documented HIV viral load less than 200 copies/mL at or within 30 days prior to study entry, OR • Group 2 (“EFV2”): for HIV-positive individuals not on ART at enrollment, planned initiation of efavirenz-based ART before or at study week 8 G. Laboratory parameters done at or within 14 days prior to screening: • Serum or plasma alanine aminotransferase (ALT) less than or equal to 3 times the upper limit of normal • Serum or plasma total bilirubin less than or equal to 2.5 times the upper limit of normal • Serum or plasma creatinine level less than or equal to 2 times the upper limit of normal • Serum or plasma potassium level greater than or equal to 3.5 meq/L • Hemoglobin level of 7.0 g/dL or greater • Platelet count of 100,000/mm3 or greater H. For all women who are not surgically sterilized or who do not meet the study definition of post-menopausal, a negative pregnancy test at or within seven (7) days prior to screening I. Karnofsky score greater than or equal to 60 J. Written informed consent Exclusion Criteria: 1. An individual meeting any of the following exclusion criteria at the time of enrollment or initiation of study drugs will be excluded from study participation: A. Pregnant or breast-feeding B. Unable to take oral medications C. Previously enrolled in this study D. Received any investigational drug in the past 3 months E. More than five (5) days of treatment directed against active tuberculosis within 6 months preceding initiation of study drugs F. More than five (5) days of systemic treatment with any one or more of the following drugs within 30 days preceding initiation of study drugs: isoniazid, rifampin, rifabutin, rifapentine, ethambutol, pyrazinamide, kanamycin, amikacin, streptomycin, capreomycin, moxifloxacin, levofloxacin, gatifloxacin, ofloxacin, ciprofloxacin, other fluoroquinolones, ethionamide, prothionamide, cycloserine, terizidone, para-aminosalicylic acid, linezolid, clofazimine, delamanid or bedaquiline G. Known history of prolonged QT syndrome H. Suspected or documented tuberculosis involving the central nervous system and/or bones and/or joints, and/or miliary tuberculosis and/or pericardial tuberculosis I. Current or planned use within six months following enrollment of one or more of the following medications: HIV protease inhibitors, HIV integrase inhibitors, HIV entry and fusion inhibitors, HIV non-nucleoside reverse transcriptase inhibitors other than efavirenz; quinidine, procainamide, amiodarone, sotalol, disopyramide, ziprasidone, or terfenadine. J. Weight less than 40.0 kg K. Known allergy or intolerance to any of the study medications L. Individuals will be excluded from enrollment if, at the time of enrollment, their M. tuberculosis isolate is already known to be resistant to any one or more of the following: rifampin, isoniazid, pyrazinamide, ethambutol, or fluoroquinolones. M. Other medical conditions, that, in the investigator’s judgment, make study participation not in the individual’s best interest. N. Current or planned incarceration or other involuntary detention. Studied Condition: N/A A150Tuberculosis of lung, confirmed by sputum microscopy with or without Studied Condition culture - B20Human Medical speciality : Infectology classification(CIE-10): immunodeficiency virus [HIV] disease resulting in infectious and parasitic diseases Countries where the enrolment is • Botswana • Sud Africa • Estados Unidos conducted: • Mali • Peru • India Number of participants per gender 250 >Number of subjects to be included (Initial): 2500 in all the countries: Number of participants per gender 0 (Posterior):

Population to be included by gender Women Men Both

Página 2 de 4 Healthy volunteers Yes No

Subordinate Groups Yes No

Indigenous or native people Yes No

Minors Yes No Indicate if the study population Subjects with disabilities to grant consent includes: Yes No Women of childbearing age Yes No

Pregnant women Yes No

Women during labor, puerperium or lactation Yes No

Fetus Yes No

Adults(18-64 years) Yes No

Elderly (>= 65 years) Yes No

Under 18 years Yes No

- In Utero Yes No Range of age of subjects to be - Preterm newborn infants (up to gestational age < 37 weeks) included: Yes No - Newborns (0-27 days) Yes No

- Infants and toddlers (28 days-23months) Yes No

- Children (2 - 11 years) Yes No

- Adolescents (12 - 17 years) Yes No 5. EVALUATION CRITERIA Primary Evaluation Criteria N° Evaluation criteria name Method of measurement Time point for the measurement Secondary Evaluation Criteria N° Evaluation criteria name Method of measurement Time point for the measurement

6. DATA MONITORING Existence of the Data Monitoring ¿Interim analysis is planned? Yes No Committee(CMD) Yes No

III. INFORMATION FROM THE FINANCING SOURCE

1. INFORMATION FROM THE FINANCING SOURCE Sponsor Name División de SIDA de los Institutos Nacionales de Salud (USA) 2. Sponsor Responsibilities Institution Name Responsibility ASOCIACIÓN CIVIL IMPACTA, SALUD Y EDUCACIÓN Inform to the OGITT of the NIH when the first subject is enrolled in Peru, and the end date of enrollment in the country. ASOCIACIÓN CIVIL IMPACTA, SALUD Y EDUCACIÓN Submit progress reports to the National Health Institute during the execution of the Clinical Trial. ASOCIACIÓN CIVIL IMPACTA, SALUD Y EDUCACIÓN Submit to the OGITT of the NIH the final reports as well as the results, conclusions, and publication of the clinical trial. ASOCIACIÓN CIVIL IMPACTA, SALUD Y EDUCACIÓN Notify to the OGITT of the NIH the adverse events and deviations as established in the Clinical Trials Regulation. ASOCIACIÓN CIVIL IMPACTA, SALUD Y EDUCACIÓN Inform and describe the reasons for a suspension and cancellation of the clinical trial. ASOCIACIÓN CIVIL IMPACTA, SALUD Y EDUCACIÓN Provide the facilities for the inspection of the execution of the clinical trial by the staff of the General Office of Research and Technology Transfer (OGITT) of the National Institute of Health. ASOCIACIÓN CIVIL IMPACTA, SALUD Y EDUCACIÓN False

IV. RESEARCH SITE, PRINCIPAL INVESTIGATOR, ETHICS COMMITTEE

Research Site 1 of 1 1. RESEARCH SITE WHERE THE CLINICAL TRIAL WILL BE CONDUCTED ASOCIACION CIVIL IMPACTA SALUD Y EDUCACION - Asociación RCI N°: 00125 Research site: Civil Impacta Salud y Educación - Sede Barranco

Página 3 de 4 2. PRINCIPAL INVESTIGATOR Full name: Mey Yeni, Leon Paredes 3. CO-INVESTIGATOR Coinvestigator 1: ROSA MERCEDES, INFANTE CASTRO Coinvestigator 2: Carlos Alberto, Mendoza Ticona Coinvestigator 3: Javier Antonio, Valencia Huamani Coinvestigator 4: Javier Ricardo, Lama Valdivia Coinvestigator 5: Jorge Luis, Sanchez Fernandez 4. INSTITUTIONAL RESEARCH ETHICS COMMITTEE (CIEI) THAT APPROVED THE TRIAL FOR THE SITE ASOCIACION CIVIL IMPACTA RCIEI N°: 00017 Ethics Committe Name: SALUD Y EDUCACION - Comite Institucional de Bioética de Impacta Approval date: 13/10/2015 End approval date: 12/10/2016 CONTACT DATA (Legal Representative of CIEI) Full Name: Andrés, Paredes Leon E-mail: [email protected] Av. Almirante Miguel Grau 1010 Telephone number: 2423072 anexo 130 Address: (Lima - Lima - Miraflores)

VI. SHARED USE OF CLINICAL TRIAL DATA (ANONIMIZED INDIVIDUAL DATA)

¿Is there a plan for sharing of Yes No Not decided deidentified individual clinical trial participant-level data (IPD) to other In case the answer is affirmative, describe the Plan: researchers (including data dictionaries)? None

Study protocol Statistical Analysis Plan Informed consent form Additional information that will be Clinical Study Report shared Others ______(Inglés) Describe briefly when this information will be available and how it can be obtained. N/A URL N/A DOI N/A Clinical Trial Registration Date 31-10-2016 00:00 Most recent Clinical Trial Update N/A

VII. CLINICAL TRIAL CONTACT PERSONS INFORMATION

DATA OF THE CONTACT PERSON(s) FOR CONSULTATIONS ABOUT THE CLINICAL TRIAL Full Name Email Telephone Type of queries to be resolved

VIII. AUTORIZATION STATUS

RESOLUCIÓN DIRECTORAL Document Document Date 31/10/2016 759-2016 Observations

Instituto Nacional de Salud - 28/09/2021 8:35 p.m.

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