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Clinical Trial Protocol Nct03660839 NCT03660839 CLINICAL TRIAL PROTOCOL Protocol title: A Randomized, Open label, Parallel-group, Single Dose Regimen, Phase 2a Study, to Investigate the Clinical and Parasiticidal Activity and the Pharmacokinetics of 3 dose levels of Artefenomel (OZ439) given in combination with Ferroquine (FQ) and FQ alone, in African Patients with Uncomplicated Plasmodium falciparum Malaria Protocol number: ACT14655 Amendment number: Not applicable Compound number OZ439 (artefenomel) and SSR97193 (ferroquine) (Trademark/INN): Short title: A Randomized, Open, Parallel-group, Single Dose, Phase 2a Study, to Investigate the Clinical and Parasiticidal Activity and the Pharmacokinetics of 3 dose levels of Artefenomel in combination with Ferroquine (FQ) and FQ alone, in African Patients with Uncomplicated Plasmodium falciparum Malaria Sponsor name and legal registered address: Regulatory agency identifying numbers: IND number: FQ: IND115244 OZ439: IND104549 UTN number: U1111-1191-5573 Approval Date: 13-Nov-2017 Total number of pages: 93 Any and all information presented in this document shall be treated as confidential and shall remain the exclusive property of Sanofi (or any of its affiliated companies). The use of such confidential information must be restricted to the recipient for the agreed purpose and must not be disclosed, published or otherwise communicated to any unauthorized persons, for any reason, in any form whatsoever without the prior written consent of Sanofi (or the concerned affiliated company); ‘affiliated company’ means any corporation, partnership or other entity which at the date of communication or afterwards (i) controls directly or indirectly Sanofi, (ii) is directly or indirectly controlled by Sanofi, with ‘control’ meaning direct or indirect ownership of more than 50% of the capital stock or the voting rights in such corporation, partnership or other entity According to template: Version Sanofi dated 01-JUN-2017 based on TransCelerate CPT version 3 Page 1 (electronic 3.0) Clinical Trial Protocol 13-Nov-2017 ACT14655 – artefenomel/ferroquine Version number: 1 Sponsor Signatory: Monitoring Team’s Representative Name and Contact Information: Property of the Sanofi Group - strictly confidential Page 2 (electronic 3.0) Clinical Trial Protocol 13-Nov-2017 ACT14655 – artefenomel/ferroquine Version number: 1 TABLE OF CONTENTS CLINICAL TRIAL PROTOCOL.......................................................................................................................1 TABLE OF CONTENTS..................................................................................................................................3 LIST OF TABLES ...........................................................................................................................................6 LIST OF FIGURES..........................................................................................................................................6 1 SYNOPSIS.......................................................................................................................................7 2 SCHEDULE OF ACTIVITIES (SOA) .............................................................................................11 3 INTRODUCTION............................................................................................................................15 3.1 STUDY RATIONALE......................................................................................................................15 3.2 BACKGROUND .............................................................................................................................16 3.3 BENEFIT/RISK ASSESSMENT.....................................................................................................16 4 OBJECTIVES AND ENDPOINTS .................................................................................................18 4.1 APPROPRIATENESS OF MEASUREMENTS ..............................................................................19 5 STUDY DESIGN ............................................................................................................................21 5.1 OVERALL DESIGN........................................................................................................................21 5.2 PARTICIPANT AND STUDY COMPLETION ................................................................................22 5.3 END OF STUDY DEFINITION.......................................................................................................22 5.4 SCIENTIFIC RATIONALE FOR STUDY DESIGN.........................................................................23 5.5 JUSTIFICATION FOR DOSE ........................................................................................................23 6 STUDY POPULATION ..................................................................................................................25 6.1 INCLUSION CRITERIA..................................................................................................................25 6.2 EXCLUSION CRITERIA ................................................................................................................26 6.3 LIFESTYLE RESTRICTIONS ........................................................................................................28 6.3.1 Meals and dietary restrictions ........................................................................................................28 6.4 SCREEN FAILURES......................................................................................................................28 7 TREATMENTS...............................................................................................................................29 Property of the Sanofi Group - strictly confidential Page 3 (electronic 3.0) Clinical Trial Protocol 13-Nov-2017 ACT14655 – artefenomel/ferroquine Version number: 1 7.1 TREATMENTS ADMINISTERED ..................................................................................................29 7.1.1 Investigational Medicinal Products.................................................................................................29 7.1.2 Noninvestigational Medicinal Products ..........................................................................................30 7.2 DOSE MODIFICATION..................................................................................................................30 7.3 METHOD OF TREATMENT ASSIGNMENT .................................................................................30 7.4 BLINDING ......................................................................................................................................31 7.5 PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY.......................................................31 7.6 TREATMENT COMPLIANCE ........................................................................................................32 7.7 CONCOMITANT THERAPY ..........................................................................................................32 7.7.1 Rescue medicine............................................................................................................................33 7.8 TREATMENT AFTER THE END OF THE STUDY........................................................................34 8 DISCONTINUATION/WITHDRAWAL CRITERIA .........................................................................35 8.1 DISCONTINUATION OF STUDY TREATMENT ...........................................................................35 8.2 WITHDRAWAL FROM THE STUDY .............................................................................................35 8.3 LOST TO FOLLOW UP .................................................................................................................35 9 STUDY ASSESSMENTS AND PROCEDURES ...........................................................................37 9.1 EFFICACY ASSESSMENTS .........................................................................................................37 9.1.1 MEASUREMENT OF PARASITEMIA............................................................................................37 9.2 ADVERSE EVENTS.......................................................................................................................39 9.2.1 Time period and frequency for collecting AE and SAE information...............................................41 9.2.2 Method of detecting AEs and SAEs...............................................................................................41 9.2.3 Follow-up of AEs and SAEs...........................................................................................................41 9.2.4 Regulatory reporting requirements for SAEs .................................................................................41 9.2.5 Cardiovascular and death events ..................................................................................................42 9.2.6 Disease-related events and/or disease-related outcomes not qualifying as AEs or SAEs ...........42 9.2.7 Pregnancy ......................................................................................................................................42 9.2.8 Guidelines for reporting product complaints ..................................................................................42 9.3 TREATMENT OF OVERDOSE......................................................................................................42
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