DATA SHEET OF CLINICAL TRIAL C.T. No 050-14

CLINICAL TRIAL REGISTRATION (EC)

I. SPONSOR INFORMATION

Foreign National

2. LEGAL PERSON 2.1 FOREIGN SPONSOR El Instituto Nacional de Alergia y El Instituto Nacional de Alergia y Registered Name: Enfermedades Infecciosas (NIAID) Registered Tradename: Enfermedades Infecciosas (NIAID) de los Estados Unidos de los Estados Unidos FOREIGN SPONSOR REPRESENTATIVE IN PERU

SUBSIDIARY: BRANCH: CRO: OTHER: ______Tradename: - TYPE OF INSTITUTION Instituto Especializado

II. CLINICAL TRIAL GENERAL INFORMATION

1. CLINICAL TRIAL IDENTIFICATION Scientific Title: EVALUATING PHARMACOKINETIC INTERACTIONS WITH VAGINAL RING CONTRACEPTIVES AND ANTIRETROVIRAL THERAPY Public Title: PK OF VAGINAL RING CONTRACEPTIVES AND ART Secundary ID(s): WHO UTN: PER-050-14 Protocol Code: A5316 Clinicaltrials.gov: NA EUDRACT N°: NA

1 1-2 2 2-3 Study clinical phase: 3 4 Clinical Trial Total Duration: 36 months No Aplica 0(exploratory trials) Enrolment start date in Peru (Initial) 15/10/2014 Worldwide enrolment start date (dd/ (dd/mm/aaaa): 05/06/2014 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 is a phase II, open-label, non-randomized, steady-state, parallel design trial to evaluate PK interactions between etonogestrel and ethinyl estradiol delivered via a vaginal ring and EFV- or ATV/r-based regimens in HIV-infected women. The study will enroll 75 women who are at least 16 years old and interested in using the NuvaRing for at least 3 weeks. Participants must be receiving EFV- or ATV/r-based ART with an HIV-1 RNA ≤400 copies/mL within 60 days prior to study entry; or not yet receiving ART, with a CD4 cell count ≥350 cells/mm3 and with no plans to initiate ART during the study period. Participants must not be pregnant, have no contraindications to receiving hormonal contraception, or be receiving medications known to interfere with either ART or hormone metabolism. Purpose To estimate the effect of ongoing ART containing either once daily ATV/r or EFV, in addition to two or more nucleosides/nucleotides, on the pharmacokinetic (PK) exposure of etonogestrel and ethinyl estradiol in HIV-infected participants at day 21 after placement of the etonogestrel/ethinyl estradiol vaginal ring (NuvaRing).

Página 1 de 4 3. STUDY INTERVENTION 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 Efavirenz 600mg Otro J05 - Antivirales de uso sistémico 2 Ritonavir Ritonavir Medicamento J05 - Antivirales de uso sistémico 3 Reyataz Atazanavir Otro J05 - Antivirales de uso sistémico 4 NuvaRing etonogestrel y etinilestradiol Producto en investigación de origen G03 - Hormonas sexuales y químico moduladores del sistema genital

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 8 weeks Subjects' follow up time 8 weeks 4. Study Population Inclusion Criteria: 1. 1. HIV-1 infection, documented. 2. Participants must be receiving either 1) EFV 600 mg daily with 2 or more NRTIs, 2) ATV/r 300 mg/ 100 mg daily with TDF 300 mg and 1 or more additional NRTIs, or 3) no ART. 3. For participants on ART, documentation of plasma HIV-1 RNA 400 copies/mL 4. For participants not on ART, CD4+ cell count must be ≥350 cells/mm3 5. Laboratory values within 60 days prior to study entry: Platelet count ≥50,000 platelets/mm3, Hb ≥8.0 g/dL, SGOT and SGPT <5 x upper limit of normal (ULN), Cr ≤1.5 x ULN,Total bilirubin ≤2.0 x ULN 6. Last menstrual period 6 months prior to study entry. 7. Premenopausal females with at least one functioning ovary. 8. Documentation of Pap smear within 1 year prior to study entry. 9. Negative serum or urine-HCG pregnancy test with a sensitivity of ≤25 mIU/mL within 60 days prior to study entry 10. All participants must agree not to participate in a conception process 11. Women age ≥18 years old. 12. Women age 16-18 years old must be ≥40kg. 13. Ability and willingness of participant or legal guardian/representative to provide informed consent. Exclusion Criteria: 1. 1. Received depot medroxyprogesterone acetate (DMPA) within 4 months prior to study entry. 2. Received other hormonal therapies within 30 days prior to study entry. 3. Breastfeeding. 4. Less than 6 weeks postpartum at study entry. 5. Use of any prohibited medications within 30 days prior to study entry 6. Initiated, discontinued, or changed doses of drugs that are CYP substrates or known to have drug interactions with ethinyl estradiol or etonogestrel 7. Bilateral oophorectomy. 8. For women older than 35 years of age, smoking 15 or more cigarettes per day. 9. History of invasive cancer of the reproductive tract. 10. Chronic immunosuppressive conditions other than HIV. 11. Use of systemic or inhaled corticosteroids such as for acute therapy for Pneumocystis pneumonia (PCP) or asthma exacerbation and prednisone ≥10 mg (or equivalent) for any reason other than a stable or tapering dose. 12. History of deep venous thrombosis or pulmonary embolism. 13. History of cerebral vascular or coronary artery disease. 14. Severe uncontrolled hypertension within 60 days prior to study entry. 15. Diabetes with vascular involvement. 16. Clinically active cervical or vaginal infection at study entry. 17. Acute infections or other opportunistic diseases requiring medication within 14 days prior to study entry. Studied Condition: N/A Studied Condition B24Unspecified human Medical speciality : Infectology classification(CIE-10): immunodeficiency virus [HIV] disease • Botswana • Sud Africa • Peru Countries where the enrolment is • Kenia • Zimbabwe • Estados Unidos conducted: • Puerto Rico • Brasil • Tailandia Number of participants per gender 10 >Number of subjects to be included (Initial): 75 in all the countries: Number of participants per gender 0 (Posterior):

Population to be included by gender Women Men Both

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

Range of age of subjects to be Adults(18-64 years) Yes No included: Elderly (>= 65 years) Yes No

Página 2 de 4 Under 18 years Yes No

- In Utero Yes No

- Preterm newborn infants (up to gestational age < 37 weeks) 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 El Instituto Nacional de Alergia y Enfermedades Infecciosas (NIAID) de los Estados Unidos 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 2. PRINCIPAL INVESTIGATOR Full name: Mey Yeni, Leon Paredes 3. CO-INVESTIGATOR Coinvestigator 1: Javier Antonio, Valencia Huamani Coinvestigator 2: Jose Armando, Gonzales Zamora Coinvestigator 3: PEDRO AUGUSTO, GONZALES SAENZ Coinvestigator 4: Alberto Martín, La Rosa Rodriguez 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: 30/07/2014 End approval date: 29/07/2015 CONTACT DATA (Legal Representative of CIEI)

Página 3 de 4 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 18-11-2014 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 18/11/2014 948-2014 Observations

Instituto Nacional de Salud - 23/09/2021 7:19 a.m.

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