RESPONSIBILITIES OF THE INVESTIGATORS The Investigators shall be responsible for ensuring that the trial is performed in accordance with the protocol and the Declaration of Helsinki (July 1999), as wel l as with the Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95) approved July 1996 and applicable regulatory requirements. These documents state that the informed consent of the patients is an essential precondition for participation in the cl inical trial. 8.1 Patient information An unconditional prerequisite for participation of a patient in the trial is the patient’s written consent after having been informed of the following: • that the trial involves research • the purpose of the trial • the trial tr eatment(s) • the trial procedures to be followed, including all invasive procedures • the patient’s responsibilities • those aspects of the trial that are experimental (e.g. novel or non- validated measurements, which are additional to normal therapeutic assessment.) • the reasonably foreseeable risks or inconveniences to the patient and, when applicable, to an embryo, foetus, or nursing infant • the reasonably expected benefits (when there is no intended clinical benefit to the patient, the patient should be made awa re of this) CT TG01 -01 Version v 10.0 27 June 2018 Confidential 76 / 87 • the alternative procedure(s) or course(s) of treatment that may be available to the patient, and their important potential benefits and risks • the compensation and/or treatment available to the patient in the event of trial- related injury • that the patient's participation in the trial is voluntary and that the patient may refuse to participate or withdraw from the trial, at any time, without penalty or loss of benefits to which the patient is otherwise entitled • that the monitor(s), the auditor(s), the Independent Ethics Committee (IEC), and the regulatory authority(ies) will be granted direct access to the patient's original medical records for verification of clinical trial procedures and/or data, without violating the confidentiality of the patie nt, to the extent permitted by the applicable laws and regulations and that, by signing a written informed consent form, the patient or the patient's legally acceptable representative is authorizing such access • that records identifying the patient will be kept confidential and, to the extent permitted by the applicable laws and/or regulations, will not be made publicly available even if the results of the trial are published • that the patient or the patient's legally acceptable representative will be informe d in a timely manner if information becomes available that may be relevant to the patient's willingness to continue to participate in the trial • the person(s) to contact for further information regarding the trial and the rights of trial patients, and whom to contact in the event of trial- related injury • the foreseeable circumstances and/or reasons under which the patient's participation in the trial may be terminated • the expected duration of the patient's participation in the trial • the approximate number of patients involved in the trial • for women, the warning that clinical studies may not be carried out in pregnant women and that pregnancy should therefore be avoided. If pregnancy occurs, the investigator must be notified immediately • insurance coverage • ment ioning that the patient may undertake additional medical treatment at any time during the clinical trial only with the express permission of the Investigators (unless indicated in an emergency) (note condition of insurance coverage in APPENDIX III) • warning that the patient may not have taken part in any other clinical trial or used any other unlicensed medication during the past 28 days • mention that any change in any concomitant medication must be reported to the Investigator immediately • permitted and non-permitted concomitant medication and dietary aspects. The information should be given to the patient both verbally and in writing. The wording must be chosen in such a way that the content is fully and readily understandable for CT TG01 -01 Version v 10.0 27 June 2018 Confidential 77 / 87 laypersons. Patients must be given sufficient time to consider their participation in the trial. 8.2 Patient consent The consent of the patient to participate in the trial has to be given in writing prior to participation in the trial. It must be signed and personally dated by the patient and by the Investigator/person designated by the Investigator to conduct the informed consent discussion. The signed and dated declaration of informed consent will remain at the Investigators’ site and must be safely archived by the Investigators so t hat the forms can be retrieved at any time for monitoring, auditing and inspection purposes. A copy of the signed and dated information and consent should be provided to the patient prior to participation and a copy maintained in the patient’s source documents if there is a separate archive file for the informed consent documents for the trial. 8.3 Ethics review The final trial protocol, including the final version of the Written Informed Consent Form, must be approved or given a favourable opinion in writing by an IEC or IRB as appropriate. The investigator must submit written approval to the sponsor before he or she can enrol any patient into the trial. The principal investigator(s) is responsible for informing the IEC or IRB of any amendment to the protocol in accordance with local requirements. In addition, the IEC or IRB must approve all advertising used to recruit patients for the trial. The protocol must be reapproved by the IEC or IRB annually, as local regulations require. Either the investigator(s) or Targovax must submit progress reports to the IEC or IRB according to local regulations and guidelines. The principal investigator(s) must also provide the IEC or IRB with any reports of SAEs from the trial site. 8.4 Source data and patient files The Invest igators have to keep a written or electronic patient file for every patient participating in the trial. This patient file should contain the available demographic and medical information of the patient, in particular the following: name, date of birth, se x, height, weight, patient history, concomitant diseases and concomitant medication (including changes during the trial), statement of entry into the trial, trial identification, the date of informed consent, all trial visit dates, predefined performed examinations and clinical findings, observed AEs (if applicable), and reason for withdrawal from the trial if applicable. It should be possible to verify the inclusion and exclusion criteria for the trial from the available data in this file. It must be possible to identify each pati ent by using this patient file. Additionally, any other documents with source data, especially original print -outs of data that were generated by technical equipment, have to be filed. All these documents have to bear at least th e patient identification number and the printing date printed by the recording device, to indicate to which patient and to which trial procedure the document belongs. Print -outs of computerised patient files must be signed and dated by the Investigators, countersigned by the monitor and kept with the Investigators’ copies of the CRF, as a CT TG01 -01 Version v 10.0 27 June 2018 Confidential 78 / 87 source document. Data are to be recorded directly onto the CRFs (i.e.