Clinical trial: NCT02403505
Section: Alternatives
Subsections: 12. **Alternatives To Participation**

This study is for research purposes only. The only alternative is to not participate in this study. This study may help us learn more about cervical HPV infection and HPV virus. The study results may be used to guide future research, treatment and prevention that could help others in the future.
Clinical trial: NCT02403505
Section: Confidentiality
Subsections: 9. **Confidentiality**

We only can do limited to protect your private information. Your study records and samples will be kept in a secure location and kept confidential in clinical trial term. We will label all of your cervical HPV samples and your study records with a code number, not your name or other personal information. However, it is possible to identify you, if necessary. And, if your HPV testing result is positive, your medical information must be open. Meanwhile, we will share your name with the lab that does the PCR tests on your HPV samples, or with anyone else who needs to know your name. Clinic staff will have access to your study records. Your records may also be reviewed by groups who watch over this study to see that we are protecting your rights, keeping you safe, and following the study plan. These groups include:  
- The sponsor, Han Xu, M.D., Ph.D., FAPCR, Sponsor-Investigator, Medical Director, Medical Monitor, Safety Officer, IRB Chair -- Health Care Provider - Individual (NPI - 1831468511)
- Any regulatory agency that reviews studies like this US Food and Drug Administration (FDA) - The Institutional Review Board (IRB), which is Medicine Invention Design Incorporation
(MIDI) IRB \#1 (IRB00009424)
- The HPV Health Care Provider and people who work for them:
✓ Medicine Invention Design Incorporation (FWA00015357) ✓ Medicine Invention Design Incorporation (IORG0007849) ✓ Health Care Provider - Group/Organization (NPI - 1023387701) ✓ Health Care Provider - Health Maintenance Organization (Code - 302R00000X) ✓ Health Care Provider - Research Clinic/Center (Code - 261QR1100X) ✓ Health Care Provider - Clinical Medical Laboratory (Code - 291U00000X) Han Xu, M.D., Ph.D., FAPCR, Sponsor-Investigator, Medical Director, Medical Monitor, Safety Officer, IRB Chair, IORG Director
Health Care Provider - Group/Organization (HMO) Call: 301-222-7143 Email: midinc@hotmail.com Enrollment ICF Form Telehealth / Telemedicine Clinical Trial Page 9 of 16  
- US Department of Health and Human Services (DHHS):
✓ Health Care Provider - Organization (NPI - 1023387701) ✓ Health Care Provider - Health Maintenance Organization (Code - 302R00000X) ✓ Health Care Provider - Research Clinic/Center (Code - 261QR1100X) ✓ Health Care Provider - Clinical Medical Laboratory (Code - 291U00000X) ✓ Health Care Provider - Individual (NPI - 1831468511)
- The US Office for Human Research Protections:
✓ FWA00015357 ✓ IORG0007849
✓ IRB00009424
All reviewers will take steps to keep your records private. We cannot guarantee absolute privacy. At this telehealth / telemedicine clinical trial site, we have to report HPV test results to local health authorities, for example, US Centers for Disease Control and Prevention (CDC). The local health authorities may also require that we share your demographic information and information about your HPV test results to support contact tracing. During your participation in this study, study staff may need to review and where necessary make and keep copies of some of your medical records (for example, records of hospitalizations). Any medical records information requested for this study will be kept confidential in the same manner as your other study records. The results of this study may be published. No publication will use your name or identify you personally. We may share information from the study with other researchers. We will not share your name or information that can identify you. A description of this study will be available on http://www.ClinicalTrials.gov. This website will not include information that can identify you. At most, the website will include a summary of the results. You can search this website at any time.
Clinical trial: NCT02403505
Section: Participant's Rights
Subsections: 13. **Your Rights And Responsibilities**

If you join the study, you have rights and responsibilities. You have many rights that we will respect. You also have responsibilities. We list these in the Bill of Rights and Responsibilities for Research. We will give you a copy of it.
Clinical trial: NCT02403505
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: 10. **Risks**|15. **Compensation For Injuries**

The potential risks associated with this study are minimal. This section describes the risks we know about. There may also be unknown risks. We will tell you if we learn anything new that may affect your willingness to stay in the study. Risks of taking blood: In this study, maybe we take blood. This procedure can cause bruising, pain, feeling faint or dizzy, soreness, redness, swelling, itching, a sore, infection, or bleeding. Taking blood can cause a low blood cell count (anemia), making you feel tired. If you become pregnant, anemia may increase the risk of complications for you or your baby, and so we may avoid your blood drawing.  
Health Care Provider - Group/Organization (HMO) Call: 301-222-7143 Email: midinc@hotmail.com Enrollment ICF Form Telehealth / Telemedicine Clinical Trial Page 10 of 16 Risks of the cervical *swab procedure:* The feeling of having a small, soft-tipped swab inserted to your cervical and twirled around may be a little uncomfortable, but it should not be painful. There is a small chance there could be some bleeding, but this is unlikely. Risks of the cervical *wash procedure:*
The *cervical* wash may be uncomfortable, but it should not be painful. There is a small chance that the sterile salt water could go into your cervical, causing you to feel a little uncomfortable, but this is unlikely.  
Risks of collecting a cervical mucus *sample:* There are no known risks of giving a sample of your cervical mucus. Urine sample collection: There are no known risks for collecting urine by routine clean catch methods. Risks of swabbing stool: There are no known risks of having your stool swabbed to collect a sample. Risks of collecting stool by a rectal swab: If you choose to provide a sample by rectal swabbing, you may feel pressure as the swab is inserted into your rectum. It may be uncomfortable, but it is usually not painful. Some people may have a little bit of bleeding. Risks of disclosure of your personal information: We will take several steps to protect your personal information. Although the risk is very low, it is possible that your personal information could be given to someone who should not have it. If that happened, you could face discrimination, stress, and embarrassment.  
Study records will be kept in secure locations in the study clinic. Study records and specimens will be labeled only with a code. All information entered into a computer is secured and will only be labelled with a code. Your names will be written on some records that are kept in the research clinic. Your study records will only be accessed by study staff given permission to do so. Study records will continue to be kept under confidential conditions according to the sponsor and IRB's guidelines and requirements.  
We cannot guarantee absolute privacy. At this telehealth / telemedicine clinical trial site, we have to report HPV test results to local health authorities, for example, US Centers for Disease Control and Prevention (CDC). The local health authorities may also require that we share your demographic information and information about your HPV test results to support contact tracing. Risks of genetic testing: If your genetic research data is shared with unauthorized users, you may be at risk of loss of the privacy of your health data. It is unlikely, but the genetic tests done on your samples could show you may be at risk for certain diseases. If others found out, it could lead to discrimination or other problems. However, it is almost impossible for you or others to know your test results from the genetic testing. The results are not part of your study records and are not given to you.

Purchase FDA approved biological products according to their labels like as following:
➢ https://dailymed.nlm.nih.gov/dailymed/
⚫ LABEL: **GARDASIL 9** - human papillomavirus 9-valent vaccine, recombinant injection, suspension NDC *0006-4119-03* BLA *125508* Packager: Merck Sharp & Dohme LLC
➢ https://dailymed.nlm.nih.gov/dailymed/
⚫ LABEL: **BCG VACCINE** - bacillus calmette-guerin substrain tice live antigen injection, powder, lyophilized, for solution NDC *0052-0603-02* BLA *103050* Packager: Merck Sharp & Dohme Corp.  
It is unlikely that you will be injured as a result of study participation. If you are injured, the clinic personnel will give you immediate necessary treatment for your injuries and refer you to the local hospital for further care as necessary. You will not have to pay for treatment provided through the public health facilities. If you receive treatment at a private facility, you and/or your medical aid will be responsible for treatment costs. There is no program to pay money or give other forms of compensation for such injuries even if they are study related through Medicine Invention Design, Inc.  
By signing and dating this document, you will not lose any of your legal rights or release anyone involved in the research from responsibility for mistakes.  
Health Care Provider - Group/Organization (HMO) Call: 301-222-7143 Email: midinc@hotmail.com Enrollment ICF Form Telehealth / Telemedicine Clinical Trial Page 12 of 16
Clinical trial: NCT02403505
Section: Procedures
Subsections: 4. **Being In The Study** Study Design:

Study Type: Interventional Primary Purpose: Treatment Study Phase: Early Phase 1 Interventional Study Model: Single Group Assignment / Single Usage / Single Dosage Number of Arms: 1 Masking: None (Open Label) Allocation: N/A Enrollment: 20 [Anticipated]
Clinical trial: NCT02403505
Section: Purpose of Research
Subsections: 1. **About The Study**|2. **Why Are We Doing This Study?**|Study Description

The HPV online clinical trial site will be doing a study to learn more about cervical HPV infection that it can treat. The online clinical trial site includes Medicine Invention Design Incorporation (Health Care Provider - Group or Organization) and online patient referral center. About 20 participants will take part in this phase 1 clinical study at single study site or multiple study sites across the United States. The sponsor-investigator in charge of this clinical study at this research center is Han Xu, M.D., Ph.D., FAPCR. The Kaiser Permanente Member HMO Health Plan can be paying for the phase 1 clinical study.

The main purpose of this study is to learn more about cervical HPV infection and how our bodies develop immune responses to it, hopefully helping us to recover from it. Your immune system is what helps to protect you against infections and disease. This information can be used in the future to help develop better treatments for cervical HPV infection, as well as may help in developing future therapeutic biological products and other prevention strategies.

Brief Summary: Conducting an initial, small, controlled clinical trial to assess HPV Antigen Presentation Therapeutic Biologics Mix activity that suggests the potential for clinical benefit of cervical HPV infection patients.  
1. Treat Infection of Multiple HPV Virus Strains. 2. Activate human HPV Trained Immunity Reaction 3. Activate human HPV Antigen Presentation Reaction. 4. The human antigen presenting cells (APCs) can treat the HPV virus protein antigens into small peptide fragments, and then clear HPV virus in vivo.  
Detailed Description:
Conducting an initial, small, controlled clinical trial to assess HPV Antigen Presentation Therapeutic Biologics Mix activity that suggests the potential for clinical benefit of cervical HPV infection patients.  
20 Cervical HPV Infection Patients Positive testing HPV by standard PCR assay HPV infection without symptoms Health Care Provider - Group/Organization (HMO) Call: 301-222-7143 Email: midinc@hotmail.com Enrollment ICF Form Telehealth / Telemedicine Clinical Trial Page 4 of 16  
No clinical signs indicative of oncology PPD negative participant is 10 TU skin test reading < 5 mm induration at 48 hours Our trial duration will be 4-week duration. 9vHPV Vaccine 1.0 mL plus BCG Vaccine 50 MG Mix Percutaneous Use with Multiple Puncture Device Our trial duration will be 4-week duration. Negative testing HPV by standard PCR assay after percutaneous use 21 days Positive skin test by 1/10 Dose 9vHPV Vaccine after to take the percutaneous use 3 weeks.
You will be in the single group, i.e., only one group. We will enroll 20 people who have no symptoms. It is possible that people who start the clinical study in the single group may be stopped the study if have side-effects. You may have about 5 study visits at 1 month, and then we will contact you online at next 2 months to check on your health.  
You can enroll at the Online Clinical Trial Site. Ask you online to take your temperature and report on your symptoms every day for about 30 days. To do this online, we will give you information about an electronic document to use, and we will show you how to use it. But there is no paper form available if you are unable to use the electronic document. There are 2 visits in the first week (day 1 and day 3), and then visits once in week 3. These visits may take place in the clinic, in your home or wherever you are staying. Some parts of these visits could be completed over the phone or through electronic communication such as text messages and email, in addition to the sample collections done in person. We will also contact you about one month after the final study visit to check on your health. If you decide to join the study, we will online review your medical history at your enrollment to see if you meet the study requirements. If you are eligible, we will online have you sign and date this consent form and collect more information about your health and medications you take. We online will also ask you about any symptoms you may have related to HPV. We may online need to review your medical records for additional information. We will also online ask you to provide the name of a person who can provide information for you if you are unable to do it yourself. At this first visit, we will do following:  
- Test HPV by standard PCR assay. BCG should not be given to individuals previously infected with M. tuberculosis. A person given the tuberculin skin test [10 tuberculin units (10 TU)
purified protein derivative (PPD)] must return within 48 hours. The positive is skin test reading > 5 mm induration at 48 hours.  
- Collect cervical swab, cervical wash, and cervical mucus samples maybe sometimes. You may be able to do these procedures yourself, or the clinic staff may do them for you.  
- Take testing PPD by Intradermal Injection (ID) assay.
The first visit could last from 1 to 2 hours.  
Health Care Provider - Group/Organization (HMO) Call: 301-222-7143 Email: midinc@hotmail.com For the online remainder of the visits, we want to collect medical information to see how your next steps develop or change over time. At these visits we will:
- Take testing HPV by standard PCR assay at week 1 day 1.  
- Take testing PPD by Intradermal Injection (ID) assay at week 1 day 1.
- Review medical information, data, results, and symptoms at week 1 day 3.  
Purchase FDA approved biological products like as following:
➢ https://dailymed.nlm.nih.gov/dailymed/
⚫ **LABEL: GARDASIL 9** - human papillomavirus 9-valent vaccine, recombinant injection, suspension NDC *0006-4119-03* BLA *125508* Packager: Merck Sharp & Dohme LLC
**Before 5 minutes** for the percutaneous route with the multiple puncture device, above biologic will be added into following biologic:
➢ https://dailymed.nlm.nih.gov/dailymed/
⚫ LABEL: **BCG VACCINE** - bacillus calmette-guerin substrain tice live antigen injection, powder, lyophilized, for solution NDC *0052-0603-02* BLA *103050* Packager: Merck Sharp & Dohme Corp.  
➢ Mix above FDA approved biological products to take the percutaneous route and treat the Infection of Multiple HPV Virus Strains.  
➢ The biological product name:
Biological Product (9vHPV Vaccine plus BCG Vaccine mix) by the percutaneous use with the multiple puncture device.  
- Take Percutaneous Use (PU) of the biological product: Biological Product (9vHPV Vaccine plus BCG Vaccine mix) by the percutaneous route **with the multiple puncture device** at week 1 day 3.  
- Ask online about any new symptoms you are having since the last time the clinic staff saw you, and after the biological product: Biological Product (9vHPV Vaccine plus BCG
Vaccine mix) by the percutaneous route **with the multiple puncture device** for this percutaneous use you were taking.  
- Collect medical information. You may be able to do this procedure yourself, or the research or referral clinic staff can do it.  
- Collect medical data. You may be able to do this procedure yourself, or the clinic staff can do it. This may depend on what the clinic staff is allowed to do and may change over time.
Health Care Provider - Group/Organization (HMO) Call: 301-222-7143 Email: midinc@hotmail.com
Clinical trial: NCT02403505
Section: Voluntary Participation
Subsections: 14. **Voluntary Participation/Leaving The Study.**

Tell us if you decide to leave the study.  
You are free to leave the study at any time and for any reason. Your care at this clinic and your legal rights will not be affected, but it is important for you to let us know. We may take you out of the study at any time.  
We may take you out of the study if: You do not follow instructions,
- We think that staying in the study might harm you, - The study is stopped for any reason.
Clinical trial: NCT02403505
Section: Withdrawal from Study
Subsections: 6. If You Are Hospitalized Or **Unable To Continue To Give Consent For Study Procedures, We Will Pause** Your Participation.

Some people with HPV develop severe symptoms and must be hospitalized. This can include being put on a ventilator to help you breathe. In the event you are not able to communicate and give consent for the study procedures to continue, we will pause your study participation. At any time that you are awake again and able to communicate, we will ask if you would like to continue participating in the study. We will only resume the study procedures if you give us permission to do so. It is also possible that you could be admitted to a hospital where the clinic staff are not able to visit you. If this happens, we will pause your study participation. When you are released from the hospital, we will ask if you would like to continue participating in the study.