This specimen will be destroyed immediately after the analysis and the results checked. 6.6 Inject ion of INO -3112 Followed by Electroporation INO-3112 will be administered, mixed in a volume of 1.1 mL by IM injection in the deltoid followed immediately by EP. If the deltoid is not a suitable location, the IM injection should be in the lateral quadriceps followed immediately by EP. Vaccination/EP must not be given within 2 cm of a tattoo, scar, or active lesion/rash or on the same side of the body where an implanted device is located . The timing of the initial dose will be as outlined above. The vaccinat ion/electroporation procedure will be performed by qualified personnel. An individual designated to perform the procedure should be permitted by the relevant local authorities to administer parenteral injections to subjects (licensed health care professionals who have appropriate credentials, e.g. MD, DO, RN, NP, PA ) in addition to satisfactorily completing device training from device company personnel. Individuals whose credentials do not meet the relevant local requirements may perform the /electroporatio n procedure under one or both of the conditions below: 42 Date: 8 April 2016 v 2.1 INO-3112 UPCC # 39313 / Inovio HPV -005 Inovio Pharmaceuticals, Inc Clinical Protocol 1. The procedure must be performed under the direct supervision of the Principal Investigator or an approved Sub-Investigator who has already been trained by device company personnel. 2. The CV and any relev ant qualifications of the individual have been reviewed and approved by the device company or its designee to perform the procedure. Any deviation from the above procedures must be approved by the Inovio Pharmaceuticals, Inc. or its designee. 6.6.1 Management of anxiety and pain due to EP procedure Subjects will be offered topical anesthetic (e.g. EMLA), to limit significant discomfort from the vaccination/EP procedure. If EMLA (lidocaine 2.5% and prilocaine 2.5%) is used, an approximately 1.5 cm diameter amount will be applied with occlusion to the site of injection ~30 minutes prior to vaccination/EP. Subjects will be offered an analgesic (e.g. ibuprofen, ketorolac) after vaccination/EP. In case subjects are anxious for the procedure, they will be offered a mild sedative (e.g. 0.5-1.0 mg lorazepam), or equivalent, as a mild sedative for anxiety related to the vaccination/EP procedure. Mild sedatives may be administered approximately 1 hour prior to EP. Subjects who receive a mild sedative should not operate a motor vehicle for 3- 4 hours after receiving medication and should have arranged transportation to depart the study site. Subjects who are allergic to or have contraindications to EMLA, ibuprofen, ketorolac or a mild sedative will be offered a suitable alternative. 6.6.2 Assessment of Injection Site Reactions When evaluating injection site reactions throughout the study, the investigator or designee will be instructed to use the following grading scale (Table 6.1): Table 6.1: Grading Scale for Injection Site Reactio ns Local Reaction to Injectable Product (Grade) Mild(1) Moderate(2) Severe(3) Potentially Life Threatening(4) Pain Does not interfere with activity Repeated use of non-narcotic pain reliever >24 hours or interferes with activity Any use of narcotic pain reliever or prevents daily activity Emergency room (ER) visit or hospitalization Tenderness Mild discomfort to touch Discomfort with movement Significant discomfort at rest ER visit or hospitalization Erythema/Redness* 2.5-5 cm 5.1-10 cm >10 cm Necrosis o r exfoliative dermatitis Induration/Swelling* * 2.5-5 cm and does not interfere with activity 5.1-10 cm or interferes with activity >10 cm or prevents daily activity Necrosis - September 2007 “FDA Guidance for Industry —Toxicity Grading Scale for Healthy A dult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials” 43 Date: 8 April 2016 v 2.1 INO-3112 UPCC # 39313 / Inovio HPV -005 Inovio Pharmaceuticals, Inc Clinical Protocol *in addition to grading the measured local reaction at the greatest single diameter, the measurement should be recorded as a continuous variable **Induration/Swelling should be evaluated and graded using the functional scale as well as the actual measurement 7 Statistical Plan 7.1 Sample Size Determination A minimal of 20 but no more than 25 eligible subjects will be enrolled , as described above. This study is an estimation study, and as such, a power calculation is not applicable.