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Writer Master Template Nabriva Therapeutics AG Clinical Protocol NAB-BC-3781-3102 Clinical Protocol No. NAB-BC-3781-3102 A Phase 3, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy and Safety of Oral Lefamulin (BC-3781) Versus Oral Moxifloxacin in Adults With Community-Acquired Bacterial Pneumonia US IND 125546 (Oral) EudraCT Number 2015-004782-92 Protocol Status Version Date Original 1.0 21-Dec-2015 Amendment 1 2.0 17-Feb-2016 Amendment 2 3.0 17-Mar-2016 The information contained herein is the property of Nabriva Therapeutics AG and may not be produced, published, or disclosed to others without written authorization of Nabriva Therapeutics AG. V3.0: 17-Mar-2016 Page 1 of 102 Confidential Information Nabriva Therapeutics AG Clinical Protocol NAB-BC-3781-3102 SPONSOR RELATED CONTACT DETAILS A Phase 3, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy and Safety of Oral Lefamulin (BC-3781) Versus Oral Moxifloxacin in Adults With Community-Acquired Bacterial Pneumonia (Protocol NAB-BC-3781-3102 with Amendments 1 and 2) Sponsor: Nabriva Therapeutics AG Leberstraße 20 1110 Vienna Austria Sponsor’s Study Managers: Patricia Spera, PhD Nabriva Therapeutics US, Inc. 1000 Continental Drive, Suite 600 King of Prussia, PA 19406 USA Tel: +1 610 816 6656 Cell: +1 610 209 5574 Email: [email protected] Claudia Lell, PhD Nabriva Therapeutics AG Leberstraße 20 1110 Vienna Austria Tel: +43 1 74093 1242 Cell: +43 664 9631469 Email: [email protected] Sponsor’s Medical Officer: Leanne Gasink, MD Senior Director, Clinical Development and Medical Affairs Nabriva Therapeutics AG Nabriva Therapeutics US, Inc. 1000 Continental Drive, Suite 600 King of Prussia, PA 19406 USA Tel: +1 610 816 6658 Cell: +1 215 880 6689 Email: [email protected] Covance’s Medical Officer: Norberto E. Soto, MD Senior Medical Director Clinical Development Services Covance, Inc. 206 Carnegie Center Princeton, NJ 08540 USA Tel: +1 609 419 2529 Cell: +1 609 216 2430 RightFax: +1 609 419 2803 Email: [email protected] V3.0: 17-Mar-2016 Page 2 of 102 Confidential Information Nabriva Therapeutics AG Clinical Protocol NAB-BC-3781-3102 INVESTIGATOR SIGNATURE PAGE A Phase 3, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy and Safety of Oral Lefamulin (BC-3781) Versus Oral Moxifloxacin in Adults With Community-Acquired Bacterial Pneumonia (Protocol NAB-BC-3781-3102 with Amendments 1 and 2) In conducting this clinical study, I agree to be responsible for: • Ensuring that the clinical investigation is conducted according to the World Medical Association Declaration of Helsinki in its revised edition (Fortaleza, Brazil, October 2013), the guidelines of International Conference on Harmonization (ICH) Good Clinical Practice (GCP) (CPMP/ICH/135/95), the signed Form Food and Drug Administration (FDA) 1572 Statement of Investigator (applies to all studies conducted under a United States Investigational New Drug Application) and other applicable local and national laws and requirements. • Protecting the rights, safety, and welfare of subjects under my care. • Maintaining control of the drugs under investigation. I also agree to conduct the study as detailed in the protocol and in accordance with Nabriva Therapeutics AG guidelines and all applicable government regulations. These guidelines and regulations include, but are not limited to: • Permission to allow Nabriva Therapeutics AG and regulatory agencies to inspect study facilities and pertinent records at reasonable times and in a reasonable manner, which ensures subject confidentiality. If I am notified that this study is to be inspected by a regulatory agency, I will notify Nabriva Therapeutics AG as soon as possible thereafter (no later than 1 week). • Submission of the proposed clinical investigation, including the protocol, the informed consent documents, and any other subject materials required for study conduct, to a duly constituted Independent Ethics Committee (IEC)/Institutional Review Board (IRB) for approval, and acquisition of written approval for each, prior to the use of the study drug. • Obtaining written informed consent only after ensuring that the subject, or his/her legal representative, is competent to make the decision, understands what is contained in the informed consent document, and is consenting voluntarily. Written informed consent will be obtained prior to administration of study drug or any non-routine study-related procedures; the document contains all the essential elements of consent and has been previously approved by the sponsor and IEC/IRB. Reference of written informed consent will be provided in source documentation. • Submission of any protocol amendment to the IEC/IRB. If the protocol amendment change(s) increase risk to the study population, full IEC/IRB written approval must be obtained prior to implementation. For changes that do not involve increased risk or affect the validity of the investigation or the subject's rights, prior IEC/IRB approval may be obtained by expedited review. V3.0: 17-Mar-2016 Page 4 of 102 Confidential Information Nabriva Therapeutics AG Clinical Protocol NAB-BC-3781-3102 • Adherence to the study protocol. Documentation and explanation of individual post- enrollment protocol deviations will be recorded in the source documentation at the site and be provided to Nabriva Therapeutics AG. • Notification to Nabriva Therapeutics AG of all serious adverse events, regardless of relationship to study drug, as specified in the protocol. Notification to the IEC/IRB of serious adverse events as specified in the protocol and per additional guidelines as provided by the IEC/IRB. • Notification to IEC/IRB of all unanticipated problems within the timeframe provided by the IEC/IRB. For the purposes of this study, unanticipated problems are defined as any incident, experience, or subject outcome that meets all of the following criteria: (1) unexpected; (2) related or possibly related to participation in the study; (3) and suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known. • Provision of adequate study oversight by personally conducting or supervising the investigation, including, but not limited to: allotting sufficient time to properly conduct and complete the study within the agreed upon time period; having available an adequate number of qualified staff and adequate facilities for the expected duration of the study and to conduct the study properly and safely; and ensuring that all persons assisting with the study are adequately informed about the protocol and the investigational product(s) and are capable of performing their study-related duties and functions. Qualifications of individuals assigned responsibility for the administration of the investigational product will be compliant with state and local law or national regulations, as applicable. • Submission of timely progress reports to the IEC/IRB and Nabriva Therapeutics AG at appropriate intervals not to exceed 1 year and submission of a final report to the IEC/IRB within the timeframe set by the IEC/IRB, but not later than 3 months after the completion or termination of the clinical investigation. • Maintenance of accurate source records from which case report forms are completed as well as drug accountability records that show the receipt and disposition (on an overall and per subject basis) of all study drug(s) shipped to the investigator by Nabriva Therapeutics AG. In addition, I agree to provide all the information requested in the eCRF presented to me by Nabriva Therapeutics AG by carefully following the completion guidelines provided as part of the eCRF. If I opt to terminate my participation in the study, the foregoing shall equally apply. Investigator’s Name (Please Print) Investigator’s Signature Date V3.0: 17-Mar-2016 Page 5 of 102 Confidential Information Nabriva Therapeutics AG Clinical Protocol NAB-BC-3781-3102 AMENDMENT 2: 17-MAR-2016 Amendment 2 addresses an inconsistency within the protocol. In accordance with Appendix 4 to the protocol, the use of strong P-glycoprotein inhibitors during study participation is prohibited. Thus, progesterone-containing products (such as oral contraceptives) are prohibited. In addition to revising the inclusion criterion associated with use of oral contraceptives, wording was added to the prohibited medications section for emphasis. These changes were made to the study synopsis, as applicable. Added text is bolded; deleted text is struck through. Section 4.1 − Inclusion Criteria #8 If female, meets the following criteria: • Surgically sterile or ≥2 years postmenopausal, or if of childbearing potential (including being <2 years postmenopausal), has a negative pregnancy test, and if participating in sexual activity that may lead to pregnancy, agrees to use an effective dual method of contraception (e.g., condom plus diaphragm, condom plus spermicide, intrauterine device plus spermicide, oral contraceptive plus condom) during the study and for ≥28 days after the last dose of study drug. If a male partner has been surgically sterile for ≥1 year, a single contraception method may be used. NOTE: The use of contraceptives containing progesterone is not permitted. Section 6.9 – Prohibited Medications Bullet #6 • Strong p-glycoprotein inhibitors (see Appendix 4) [NOTE: The use of contraceptives containing progesterone is not permitted.] AMENDMENT 1: 17-FEB-2016 Amendment 1 addresses revisions to the protocol
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