Conducting an Early Phase Clinical Trial to Assess for CEA Antigen Presentation Therapeutic Biological Product Mix Activity That Suggests the Potential for Clinical Benefits of CEA Positive Rectal Cancer Patients.
Phase: PHASE1
Conditions: Rectal Cancer
Sponsor: Han Xu, M.D., Ph.D., FAPCR, Sponsor-Investigator, IRB Chair

Cover Page 
 
 
 
Release Date: August 27, 2024    
 
ClinicalTrials.gov ID: NCT02403505     
 
Unique Protocol ID: IND 172259    
 
Brief Title: Early Phase Clinical Trial About Therapeutic Biological Product Mix for 
Treating CEA Positive Rectal Cancer (CEA+RC-BCG)  
 
Official Title: Conducting an Early Phase Clinical Trial to Assess for CEA Antigen Presentation 
Therapeutic Biological Product Mix Activity That Suggests the Potential for 
Clinical Benefits of CEA Positive Rectal Cancer Patients.  
 
Secondary IDs: FWA00015357 [Registry ID: HHS, Human Protections Administrator] 
IRB00009424 [Registry ID: HHS, IRB] 
IORG0007849 [Registry ID: HHS, IORG] 
NPI-1831468511 [Registry ID: HHS, Health Care Provider Individual] 
NPI-1023387701 [Registry ID: HHS, Health Care Provider Organization]  
IND 172259 [Registry ID: FDA, Investigational New Drug Application (IND)]   
 
Human APCs treat CEA protein into small fragments, and then kill CEA (+) RC cells in vivo.  

1 
 
6. Protocol [21 CFR 312.23(a)(6)]  
6a. Study protocol [21 CFR 312.23(a)(6)]  
 
Contents 
 
21 CFR§312.23 (a)(6) .......................................................................................................................... 2 
Protocols. ............................................................................................................................................. 2 
(i) 
A protocol for each planned study. (Protocols for studies not submitted initially in the IND should be 
submitted in accordance with § 312.30(a).) In general, protocols for Phase 1 studies may be less detailed 
and more flexible than protocols for Phase 2 and 3 studies. Phase 1 protocols should be directed primarily 
at providing an outline of the investigation - an estimate of the number of patients to be involved, a 
description of safety exclusions, and a description of the dosing plan including duration, dose, or method 
to be used in determining dose - and should specify in detail only those elements of the study that are 
critical to safety, such as necessary monitoring of vital signs and blood chemistries. Modifications of the 
experimental design of Phase 1 studies that do not affect critical safety assessments are required to be 
reported to FDA only in the annual report. ................................................................................................... 2 
(ii) 
In Phases 2 and 3, detailed protocols describing all aspects of the study should be submitted. A 
protocol for a Phase 2 or 3 investigation should be designed in such a way that, if the sponsor anticipates 
that some deviation from the study design may become necessary as the investigation progresses, 
alternatives or contingencies to provide for such deviation are built into the protocols at the outset. For 
example, a protocol for a controlled short-term study might include a plan for an early crossover of 
nonresponders to an alternative therapy. .................................................................................................... 4 
(iii) 
A protocol is required to contain the following, with the specific elements and detail of the 
protocol reflecting the above distinctions depending on the phase of study: ............................................. 5 
(a) 
A statement of the objectives and purpose of the study. .................................................................. 5 
(b) 
The name and address and a statement of the qualifications (curriculum vitae or other statement of 
qualifications) of each investigator, and the name of each sub-investigator (e.g., research fellow, resident) working 
under the supervision of the investigator; the name and address of the research facilities to be used; and the name 
and address of each reviewing Institutional Review Board. ............................................................................... 5 
(c) 
The criteria for patient selection and for exclusion of patients and an estimate of the number of 
patients to be studied. ................................................................................................................................ 9 
(d) 
A description of the design of the study, including the kind of control group to be used, if any, and a description 
of methods to be used to minimize bias on the part of subjects, investigators, and analysts. .............................. 10 
(e) 
The method for determining the dose(s) to be administered, the planned maximum dosage, and the 
duration of individual patient exposure to the drug. ................................................................................ 12 
(f) 
A description of the observations and measurements to be made to fulfill the objectives of the study. ....... 13 
(g) 
A description of clinical procedures, laboratory tests, or other measures to be taken to monitor the 
effects of the drug in human subjects and to minimize risk. ................................................................... 13 
 
 
It is my commitment that our Institutional Review Board (IRB) (IRB00009424) that complies with the 
requirements set forth in part 56 will be responsible for the initial and continuing review and approval of 
each of the studies in my proposed clinical investigation and that the sponsor-investigator (me i.e. Han Xu, 
M.D., Ph.D.) will report to our IRB (IRB00009424) the proposed changes in my research activity in accordance 
with the requirements of part 56.  
 
I write the statement with respect to each clinical study involving human subjects that it either will be 
conducted in compliance with the institutional review board regulations in part 56 or will not be subject to 
the regulations under §56.104 or §56.105; and that it either will be conducted in compliance with the 
informed consent regulations in part 50 or will not be subject to the regulations under §50.23 and §50.24.  
 

2 
 
21 CFR§312.23 (a)(6)  
Protocols.  
 
(i) A protocol for each planned study. (Protocols for studies not submitted initially in the IND should 
be submitted in accordance with § 312.30(a).) In general, protocols for Phase 1 studies may be 
less detailed and more flexible than protocols for Phase 2 and 3 studies. Phase 1 protocols should 
be directed primarily at providing an outline of the investigation - an estimate of the number of 
patients to be involved, a description of safety exclusions, and a description of the dosing plan 
including duration, dose, or method to be used in determining dose - and should specify in detail 
only those elements of the study that are critical to safety, such as necessary monitoring of vital 
signs and blood chemistries. Modifications of the experimental design of Phase 1 studies that do 
not affect critical safety assessments are required to be reported to FDA only in the annual report.  
 
The protocol for the planned IND 172259 Phase 1 clinical study NCT02403505:  
In general, protocols for Phase 1 studies may be less detailed and more flexible. Phase 1 protocol 
of the planned IND 172259 clinical study NCT02403505 will be directed primarily at providing an 
outline of the clinical investigation NCT02403505 like as following:  
 
➢ An estimate of the number of patients to be involved:  
 20 CEA positive rectal cancer Patients  
➢ A description of participant inclusions:  
 Positive testing CEA by blood-drawing assay  
 TB negative participant is negative IGRA blood test with TB antigens   
 Clinical Rectal Cancer Diagnosis Stage 0 - IIA  
 Clinical Rectal Cancer Diagnosis without symptoms  
 Clinical Rectal Cancer Diagnosis without metastasis  
➢ A description of safety exclusions:   
 Pregnant 
 Thrombosis 
 Allergy  
 TB positive participant is positive IGRA blood test with TB antigens  
 Symptoms of Rectal Cancer   
 Metastasis of Rectal Cancer  
 Evidence of critical illness  
➢ A description of the dosing plan:  
 Duration: 4-weeks = 28-days  
 Dose: MS CEA Antigen Protein 0.05 mg plus BCG Vaccine 50 MG Mix 
⚫ 1 Dose i.e., 1 mL - 0.05 mg CEA protein antigen  
Millipore - https://www.sigmaaldrich.com/US/en/product/mm/219369 
Millipore-Sigma CEA Antigen Protein   
Product name: Carcinoembryonic Antigen, Human Colon Adenocarcinoma Cell Line  
Pack Size: 0.1 mg  
Product Number: 219369  
Catalogue No.: D44022  
Brand: Millipore  
Company: Sigma-Aldrich Inc.   
➢ Add 2 mL distilled water into above 0.1 mg CEA protein antigen  
 Before 5 minutes for the percutaneous route with the multiple puncture device, above 
biologic 1 mL - 0.05 mg CEA will be added into following biologic BCG:   
⚫ 1 Dose i.e., 50 mg wet weight organism i.e., 1 Intact Vial of lyophilized powder like as 
following:  

3 
 
Dailymed - 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.  
Active Ingredient(s) and Strength(s) like as following:  
BCG VACCINE contains live bacteria. BCG VACCINE for percutaneous use is an attenuated, 
live culture preparation of the Bacillus of Calmette and Guerin (BCG) strain of 
Mycobacterium bovis. The TICE® strain used in this BCG VACCINE preparation. The TICE® BCG 
organism is grown for preparation of freeze-dried cake.  
✓ Bacillus of Calmette and Guerin (BCG) strain of Mycobacterium bovis  
✓ 1 to 8 × 10^8 colony forming units (CFU) of BCG (equivalent to approximately 50 mg wet weight)  
✓ Merck TICE® BCG organism 50 MG wet weight  
 The method to be used in determining dose:  
 Purchased below FDA approved biological products according to labels:  
 MS CEA Antigen Protein 0.05 mg plus BCG Vaccine 50 MG Mix:  
⚫ 1 Dose i.e., 1 mL - 0.05 mg CEA protein antigen  
Millipore - https://www.sigmaaldrich.com/US/en/product/mm/219369  
Millipore-Sigma CEA Antigen Protein   
Product name: Carcinoembryonic Antigen, Human Colon Adenocarcinoma Cell Line  
Pack Size: 0.1 mg  
Product Number: 219369  
Catalogue No.: D44022  
Brand: Millipore  
Company: Sigma-Aldrich Inc.     
 Before 5 minutes for the percutaneous route with the multiple puncture device, above 
biologic 1 mL - 0.05 mg CEA will be added into following biologic BCG:  
⚫ 1 Dose i.e., 50 mg wet weight organism i.e., 1 Intact Vial of lyophilized powder like as 
following:  
Dailymed - 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.  
 
 We will specify in detail only those elements of the IND 172259 Phase 1 clinical study 
NCT02403505 that are critical to safety, such as necessary monitoring of vital signs and 
blood chemistries.  
⚫ The vital signs of safety exclusions:   
✓ Pregnant 
✓ Thrombosis 
✓ Allergy  
✓ Positive IGRA blood test with TB antigens  
✓ Symptoms of rectal cancer   
✓ Metastasis of rectal cancer   
✓ Evidence of critical illness  
 
 Modifications of the experimental design of Phase 1 studies that do not affect critical safety 
assessments are required to be reported to FDA only in the annual report. 
 

4 
 
21 CFR § 312.30  
(a) New protocol. Whenever a sponsor intends to conduct a study that is not covered by a protocol 
already contained in the IND, the sponsor shall submit to FDA a protocol amendment containing 
the protocol for the study. Such study may begin provided two conditions are met:  
(1) The sponsor has submitted the protocol to FDA for its review; and  
(2) the protocol has been approved by the Institutional Review Board (IRB) with responsibility 
for review and approval of the study in accordance with the requirements of part 56. The 
sponsor may comply with these two conditions in either order. 
 
Phase 1 protocols will be directed primarily at providing an outline of the investigation: 
⚫ An estimate of the number of patients to be involved:  
✓ 20 CEA positive rectal cancer patients  
⚫ A description of safety exclusions:  
✓ Pregnant 
✓ Thrombosis 
✓ Allergy  
✓ IGRA blood test positive participant is positive IGRA blood test with TB antigens  
✓ Symptoms of rectal cancer   
✓ Metastasis of rectal cancer   
✓ Evidence of critical illness  
⚫ A description of the dosing plan for duration:  
✓ Our trial duration will be 4-week duration. 
⚫ A description of the dosing plan for dose:  
✓ CEA protein antigen 0.05 MG plus BCG Vaccine 50 MG Mix  
⚫ A description of the dosing plan for method to be used in determining dose:   
✓ Millipore-Sigma CEA Antigen Protein   
Product name: Carcinoembryonic Antigen, Human Colon Adenocarcinoma Cell Line  
Pack Size: 0.1 mg  
Product Number: 219369  
Catalogue No.: D44022  
Brand: Millipore  
Company: Sigma-Aldrich Inc.  
 Before 5 minutes for the percutaneous route with the multiple puncture device, above 
biologic 1 mL - 0.05 mg CEA will be added into following biologic BCG:  
✓ 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.  
 
⚫ The elements of the study that are critical to safety:  
➢ The necessary monitoring of vital signs:  
✓ Positive IGRA blood test with TB antigens  
✓ Positive testing CEA by blood-drawing   
 
(ii) In Phases 2 and 3, detailed protocols describing all aspects of the study should be submitted. 
A protocol for a Phase 2 or 3 investigation should be designed in such a way that, if the 
sponsor anticipates that some deviation from the study design may become necessary as 
the investigation progresses, alternatives or contingencies to provide for such deviation are 
built into the protocols at the outset. For example, a protocol for a controlled short-term 
study might include a plan for an early crossover of nonresponders to an alternative therapy.  
 
The IND 172259 Phase 1 clinical study need not describe Phases 2 and 3 protocols.  
 

5 
 
(iii) A protocol is required to contain the following, with the specific elements and detail of the 
protocol reflecting the above distinctions depending on the phase of study:  
 
(a) A statement of the objectives and purpose of the study.  
 
1. Treat CEA positive rectal cancer.  
2. Activate human CEA protein Antigen Presentation Reaction.  
3. The human antigen presenting cells (APCs) can treat the CEA protein antigen into small 
peptide fragments, and then kill CEA positive rectal cancer cells in vivo.  
 
Statement 
 
The objectives and purpose of the IND 172259 Phase 1 clinical study will be 1 dose of the biological product, 
CEA protein antigen add into 1 dose of the biological product, BCG VACCINE and mix above them before 
5 minutes to take the percutaneous use and treat the Infection of Multiple HPV Virus Strains.  
 
(b) The name and address and a statement of the qualifications (curriculum vitae or other statement of 
qualifications) of each investigator, and the name of each sub-investigator (e.g., research fellow, 
resident) working under the supervision of the investigator; the name and address of the research 
facilities to be used; and the name and address of each reviewing Institutional Review Board.  
 
Contact Person: Han Xu, M.D., Ph.D., FAPCR, Sponsor-Investigator, IRB Chair, Medical Director  
Contact Company: Medicine Invention Design Incorporation  
Contact Address: 5545 Burnside Drive, Rockville, MD 20853, USA  
Contact Call: 001-301-222-7143  
Contact Fax: 001-866-458-0099  
Contact Email: hanxumdphd@midinc.us  
 
The name of investigator:  
➢ Han Xu, M.D., Ph.D., FAPCR, Sponsor-Investigator, IRB Chair, Medical Director  
Health Care Provider - Individual (NPI - 1831468511)  
The address of investigator: (Online Clinical Trial Site)  
➢ 5545 Burnside Drive, Rockville, MD 20853, USA  
The statement of the qualifications of investigator:  
21 CFR 312.53(c)(1) 
A signed investigator statement (Form FDA-1572) containing:  
(i) The name and address of the investigator:  
➢ The name of the investigator:  
✓ Han Xu, M.D., Ph.D., FAPCR, Sponsor-Investigator, IRB Chair, Medical Director 
➢ The address of the investigator: (Online Clinical Trial Site)  
✓ 5545 Burnside Drive, Rockville, MD 20853, USA 
(ii) The name and code number, if any, of the protocol(s) in the IND identifying the 
study(ies) to be conducted by the investigator:  
✓ Han Xu, M.D., Ph.D., FAPCR, Sponsor-Investigator, IRB Chair, Medical Director  
✓ Health Care Provider - Individual (NPI - 1831468511)  
✓ Health Care Provider - Clinical Ethicist (Code - 174V00000X)  
✓ Health Care Provider - Research Study Specialist (Code - 1744R1102X)  
✓ Health Care Provider - Pharmacist - Clinical Pharmacy Specialist (Code - 1835P0018X)   
✓ IND Number: IND 172259  
✓ ClinicalTrials.gov ID: NCT02403505  
(iii) The name and address of any medical school, hospital, or other research facility where 
the clinical investigation(s) will be conducted:  
➢ The name of research facility:  

6 
 
✓ Medicine Invention Design Incorporation  
✓ Medicine Invention Design Incorporation (FWA00015357)  
✓ Medicine Invention Design Incorporation (IORG0007849)  
✓ CAQH Approved Maryland State License (D11379922)  
✓ 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 - Multi-Specialty Group - (Code - 193200000X)  
✓ Health Care Provider - Pharmacist - Clinical Pharmacy Specialist (Code - 1835P0018X) 
➢ The address of research facility: (Online Clinical Trial Site)  
✓ 5545 Burnside Drive, Rockville, MD 20853, USA  
(iv) The name and address of any clinical laboratory facilities to be used in the study:  
➢ The name of clinical laboratory facility:  
✓ Medicine Invention Design Incorporation  
✓ Medicine Invention Design Incorporation (FWA00015357)  
✓ Medicine Invention Design Incorporation (IORG0007849)  
✓ Health Care Provider - Research Clinic/Center (Code - 261QR1100X)  
✓ Health Care Provider - Clinical Medical Laboratory (Code - 291U00000X)  
➢ The address of clinical laboratory facility: (Online Clinical Trial Site)  
✓ 5545 Burnside Drive, Rockville, MD 20853, USA  
(v) The name and address of the IRB that is responsible for review and approval of the study(ies):   
➢ The name of the IRB:  
✓ Medicine Invention Design Incorporation  
✓ Medicine Invention Design Incorporation (FWA00015357)  
✓ Medicine Invention Design Incorporation (IORG0007849)  
✓ Medicine Invention Design Incorporation (MIDI) IRB #1 (IRB00009424)  
✓ Health Care Provider - Clinical Ethicist (Code - 174V00000X)  
➢ The address of the IRB: (Online Clinical Trial Site)  
✓ 5545 Burnside Drive, Rockville, MD 20853, USA  
(vi) A commitment by the investigator that he or she:  
(a) Will conduct the study(ies) in accordance with the relevant, current protocol(s) and 
will only make changes in a protocol after notifying the sponsor, except when 
necessary to protect the safety, the rights, or welfare of subjects;  
(b) Will comply with all requirements regarding the obligations of clinical 
investigators and all other pertinent requirements in this part;  
(c) Will personally conduct or supervise the described investigation(s);  
(d) Will inform any potential subjects that the drugs are being used for investigational 
purposes and will ensure that the requirements relating to obtaining informed consent 
(21 CFR part 50) and institutional review board review and approval (21 CFR part 56) 
are met;  
(e) Will report to the sponsor adverse experiences that occur in the course of the 
investigation(s) in accordance with § 312.64;  
(f) Has read and understands the information in the investigator's brochure, including 
the potential risks and side effects of the drug; and  
21 CFR 312.55(a) 
Before the investigation begins, a sponsor (other than a sponsor-investigator) shall 
give each participating clinical investigator an investigator brochure containing the 
information described in § 312.23(a)(5). 
(g) Will ensure that all associates, colleagues, and employees assisting in the conduct of 
the study(ies) are informed about their obligations in meeting the above commitments. 
 

7 
 
Commitment 
 
Han Xu, M.D., Ph.D., FAPCR, Sponsor-Investigator 
 
A commitment by the sponsor-investigator that I:  
(a) Will conduct the study (NCT02403505) in accordance with the relevant, current 
protocol(s) and will only make changes in a protocol after notifying the sponsor, except 
when necessary to protect the safety, the rights, or welfare of subjects.  
(b) Will comply with all requirements regarding the obligations of clinical investigators and 
all other pertinent requirements in this part.  
(c) Will personally conduct or supervise the described investigation(s).   
(d) Will inform any potential subjects that the drugs are being used for investigational 
purposes and will ensure that the requirements relating to obtaining informed consent (21 
CFR part 50) and institutional review board review and approval (21 CFR part 56) are met;  
(e) Will report to the sponsor (Han Xu, M.D. Ph.D., FAPCR) adverse experiences that occur 
in the course of the investigation(s) in accordance with § 312.64.   
(f) Have read and understands the information in the investigator's brochure, including the 
potential risks and side effects of the drug.   
21 CFR 312.55(a) 
Han Xu, Sponsor-Investigator, need not give an investigator brochure containing the 
information described in § 312.23(a)(5). 
(g) Will ensure that all associates, colleagues, and employees assisting in the conduct of the study 
(NCT02403505) are informed about their obligations in meeting the above commitments.  
 
(vii) A commitment by the investigator that, for an investigation subject to an institutional 
review requirement under part 56, an IRB that complies with the requirements of that part 
will be responsible for the initial and continuing review and approval of the clinical 
investigation and that the investigator will promptly report to the IRB all changes in the 
research activity and all unanticipated problems involving risks to human subjects or others, 
and will not make any changes in the research without IRB approval, except where 
necessary to eliminate apparent immediate hazards to the human subjects.  
 
Commitment 
 
Han Xu, M.D., Ph.D., FAPCR, Sponsor-Investigator, IRB Chair, Medical Director  
 
It is my commitment that our Institutional Review Board (IRB) (IRB00009424) that complies 
with the requirements set forth in part 56 will be responsible for the initial and continuing 
review and approval of each of the studies in my proposed clinical investigation and that the 
sponsor-investigator (me i.e. Han Xu, M.D., Ph.D.) will report to our IRB (IRB00009424) the 
proposed changes in my research activity in accordance with the requirements of part 56.  
 
(viii) A list of the names of the sub-investigators (e.g., research fellows, residents) who 
will be assisting the investigator in the conduct of the investigation(s).  
 
Not available right now  
 
The name of the research facility:  
➢ Medicine Invention Design Incorporation (MIDI)  
✓ Medicine Invention Design Incorporation (FWA00015357)  
✓ Medicine Invention Design Incorporation (IORG0007849)  
✓ Health Care Provider - Group/Organization (NPI - 1023387701)  
✓ Health Care Provider - Research Clinic/Center (Code - 261QR1100X)  
✓ Health Care Provider - Multi-Specialty Group - (Code - 193200000X)  
✓ Health Care Provider - Pharmacist - Clinical Pharmacy Specialist (Code - 1835P0018X) 
The address of the research facility: (Virtual / Mobile / Online)  
➢ 5545 Burnside Drive, Rockville, MD 20853, USA  
 

8 
 
The name of Institutional Review Board:  
➢ Medicine Invention Design Incorporation (MIDI) IRB #1 (IRB00009424) 
➢ Health Care Provider - Individual (NPI 1831468511)  
➢ Health Care Provider - Clinical Ethicist (Code - 174V00000X)  
The address of Institutional Review Board: (Virtual / Mobile / Online)  
➢ 5545 Burnside Drive, Rockville, MD 20853, USA  
 
21 CFR 312.53(c)(2) 
Curriculum vitae. A curriculum vitae or other statement of qualifications of the investigator 
showing the education, training, and experience that qualifies the investigator as an expert in 
the clinical investigation of the drug for the use under investigation.  
 
The statement of the qualifications of sponsor-investigator:  
The education, training, and experience that qualifies the sponsor-investigator as an 
expert in the IND 172259 Phase 1 clinical investigation of FDA approved biological products 
for the use under the IND 172259 Phase 1 clinical investigation:  
 
The information about medical and scientific training of sponsor-investigator (SI) 
Han Xu, M.D., Ph.D., FAPCR, Sponsor-Investigator, IRB Chair, IORG Director 
 
The information about medical and scientific experience of sponsor-investigator (SI)  
➢ Han Xu, M.D., Ph.D., FAPCR, Sponsor-Investigator, IRB Chair, IORG Director  
➢ 1980-1986 - M.D., Ph.D. accepted by NIH; Beijing Medical University School of Basic Medical Science; 
Beijing, China  
Dr. Han Xu received clinical education and clinical training in 1980-1986.  
➢ 1986-1995 - Principal Investigator (PI), Clinical Attending Physician, Beijing Clinical Research Institute, 
Beijing Friendship Hospital; Beijing, China  
Dr. Han Xu received clinical training and had clinical experience in 1986-1995.  
➢ 1995-2000 - M.D., Ph.D. accepted by NIH; Visiting Scholar, NCI-Frederick, National Cancer Institute 
(NCI), National Institutes of Health (NIH); Frederick, Maryland  
Dr. Han Xu received clinical investigator training in 1995-2000  
➢ 2000-2006 - Principal Investigator (PI) / Program Director (PD), Pharm1 Incorporation - Beijing Office; 
Beijing, China  
➢ 2006 - Sponsor-Investigator (SI) / IRB Chair (Study Chair, SC) / IORG Director (Study Director, SD) / 
Medical Monitor (MM) / Safety Officer (SO), Medicine Invention Design Incorporation (MIDI); 
Rockville, Maryland   
INSTITUTION / UNIVERSITY  
DEGREE / 
TRAINING  
Start Date 
MM/YYYY 
End Date 
MM/YYYY 
FIELD OF STUDY 
Beijing Medical University (BMU)  
School of Basic Medical Sciences (SBMS)  
B.S. 
0719/86  
 
Basic and Clinical 
Medicines  
Beijing Medical University (BMU)  
School of Basic Medical Sciences (SBMS)  
Department of Medicine  
Internship 
09/1984 
08/1985 
Clinical Medicines  
Beijing Medical University (BMU)  
School of Basic Medical Sciences (SBMS) 
Internship 
09/1985 
07/1986 
Basic Medicines  
Beijing Friendship Hospital (BFH)   
Beijing Clinical Research Institute (BCRI)  
Residency 
Physician  
07/1986  
06/1991  
Internal Medicine   
NIH-NCI accepted my degree obtained in BMU 
like as USA equivalent doctorate titles  
M.D.  
Ph.D.  
07/1986  
 
Basic and Clinical 
Medicines  
National Institutes of Health (NIH)  
National Cancer Institute (NCI)  
Visiting 
Scholar  
12/1995  
03/2000 
Basic and Clinical 
Research  

9 
 
➢ 2013 - Director Member, Medicine Invention Design Incorporation (MIDI) (IORG0007849) - Institution or 
Organization (IORG) of Registration at U.S. Department of Health and Human Services (HHS)  
➢ 2013 - Board Member and Chair, Medicine Invention Design Incorporation (MIDI) IRB #1 (IRB00009424) - 
Institutional Review Board (IRB) of Registration at U.S. Department of Health and Human Services (HHS)  
Dr. Han Xu had already been Sponsor-Investigator (SI) approved by IRB00009424.  
➢ 2020 - Active Member, Fellow of the APCR (FAPCR), Academy of Physicians in Clinical Research (APCR) 
- APCR Membership Eligibility - Physician Investigator  
⚫ Certificate of Fellow of Academy of Physicians in Clinical Research (FAPCR)  
⚫ Academy of Physicians in Clinical Research (APCR)  
 PI (Principal Investigator) in clinical trials  
 Medical Director of Clinical Research Site  
➢ 2023 - CAQH Approved Maryland State License (D11379922)  
⚫ Medicine Invention Design, Inc.  
⚫ Health Care Provider - Group/Organization (NPI - 1023387701)  
⚫ Health Care Provider - Health Maintenance Organization (HMO) (Code - 302R00000X)  
⚫ Health Care Provider - Multi-Specialty Group - (Code - 193200000X)  
⚫ Health Care Provider - Pharmacist - Clinical Pharmacy Specialist (Code - 1835P0018X)  
➢ 2024 - FDA Pre-Assignment - My IND has been granted. My pre-assigned number is 172259.  
⚫ Individual Sponsor: HAN XU  
⚫ Organization Sponsor: Medicine Invention Design Incorporation  
➢ 2024 update - ClinicalTrials.gov ID: NCT02403505 under 42 CFR Part 11  
⚫ Responsible Party (Sponsor-Investigator)  
⚫ Study Principal Investigator [Principal Investigator (PI)]  
⚫ Study Director (Medical Director)  
⚫ Study Chair (IRB Chair)  
 
➢ The qualifications of sponsor-investigator:  
 Han Xu, M.D., Ph.D., FAPCR, Sponsor-Investigator, Medical Director, IRB Chair  
 NPI 1831468511 - Individual  
 Clinical Ethicist - (Code - 174V00000X)  
 Specialist Research Study - (Code - 1744R1102X)  
 ClinicalTrials.gov ID: NCT02403505 [Responsible Party (Sponsor-Investigator)]  
 FWA00015357 (Human Protections Administrator)  
➢ Medicine Invention Design Incorporation (MIDI) (IORG0007849)  
➢ Medicine Invention Design Incorporation (MIDI) IRB #1 (IRB00009424)  
➢ Federal-wide Assurance (FWA) for the Protection of Human Subjects (FWA00015357)  
➢ CAQH Approved Maryland State License (D11379922)  
 NPI 1023387701 - Organization  
 Research Clinic/Center - (Code - 261QR1100X)  
 Clinical Medical Laboratory - (Code - 291U00000X)  
 Health Maintenance Organization - (Code - 302R00000X)  
 Health Care Provider - Multi-Specialty Group - (Code - 193200000X)  
 Health Care Provider - Pharmacist - Clinical Pharmacy Specialist (Code - 1835P0018X)  
 
(c) The criteria for patient selection and for exclusion of patients and an estimate of the 
number of patients to be studied.  
 
The criteria for patient selection:  
✓ CEA Positive Rectal Cancer Patients  
✓ Clinical Rectal Cancer Diagnosis Stage 0 - IIA  
✓ Clinical Rectal Cancer Diagnosis without symptoms  
✓ Clinical Rectal Cancer Diagnosis without metastasis  
✓ Positive testing CEA by blood-drawing   
✓ TB negative participant is negative IGRA blood test with TB antigens. 
 

10 
 
The criteria for patient exclusion: 
✓ Pregnant 
✓ Thrombosis 
✓ Allergy  
✓ TB participant is positive IGRA blood test with TB antigens.  
✓ Symptoms of rectal cancer   
✓ Metastasis of rectal cancer   
✓ Evidence of critical illness  
 
(d) A description of the design of the study, including the kind of control group to be used, if any, 
and a description of methods to be used to minimize bias on the part of subjects, investigators, 
and analysts.  
 
➢ Study Type: Interventional  
➢ Primary Purpose: Treatment 
➢ Study Phase: Phase 1 Clinical Trial  
➢ Interventional Study Model: Single Group Assignment / Single Usage / Single Dosage 
➢ Number of Arms: 1 / single-arm study  
➢ Masking: None (Open Label) 
➢ Allocation: N/A 
➢ Enrollment:  
✓ 20 CEA Positive Rectal Cancer Patients  
✓ Clinical Rectal Cancer Diagnosis Stage 0 - IIA  
✓ Clinical Rectal Cancer Diagnosis without symptoms  
✓ Clinical Rectal Cancer Diagnosis without metastasis  
✓ Positive testing CEA by blood-drawing   
✓ TB negative participant is negative IGRA blood test with TB antigens.  
➢ Dose: CEA protein antigen 0.05 mg plus BCG Vaccine 50 MG Mix  
⚫ 1 Dose i.e., 1 mL - 0.05 mg CEA protein antigen like as following:  
https://www.sigmaaldrich.com/US/en/product/mm/219369  
Millipore-Sigma CEA Antigen Protein  
Product name: Carcinoembryonic Antigen, Human Colon Adenocarcinoma Cell Line  
Pack Size: 0.1 mg  
Product Number: 219369  
Catalogue No.: D44022  
Brand: Millipore  
Company: Sigma-Aldrich Inc.  
 Add 2 mL distilled water into above 0.1 mg CEA protein antigen  
 Before 5 minutes for the percutaneous route with the multiple puncture device, above 
biologic 1 ml - 0.05 mg CEA will be added into following biologic BCG:  
⚫ 1 Dose i.e., 50 mg wet weight organism i.e., 1 Intact Vial of lyophilized powder like 
as following:  
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.  
➢ Route: Percutaneous Use with Multiple Puncture Device  
➢ Duration: Our trial duration will be 4-week duration.  
➢ Endpoint: Positive IGRA blood test with CEA protein antigen after percutaneous use 21 days.  
Rectal Cancer without growth or metastasis  
 

11 
 
The methods to be used to minimize bias on the part of subjects, investigators, and 
analysts:  
21 CFR 312.53(c)(1) 
(vi) A commitment by the investigator that he or she:  
(a) Will conduct the study(ies) in accordance with the relevant, current protocol(s) 
and will only make changes in a protocol after notifying the sponsor, except when 
necessary to protect the safety, the rights, or welfare of subjects;  
(b) Will comply with all requirements regarding the obligations of clinical 
investigators and all other pertinent requirements in this part;  
(c) Will personally conduct or supervise the described investigation(s);  
(d) Will inform any potential subjects that the drugs are being used for 
investigational purposes and will ensure that the requirements relating to 
obtaining informed consent (21 CFR part 50) and institutional review board 
review and approval (21 CFR part 56) are met;  
(e) Will report to the sponsor adverse experiences that occur in the course of the 
investigation(s) in accordance with § 312.64;  
(f) Has read and understands the information in the investigator's brochure, 
including the potential risks and side effects of the drug; and  
21 CFR 312.55(a) 
Before the investigation begins, a sponsor (other than a sponsor-investigator) 
shall give each participating clinical investigator an investigator brochure 
containing the information described in § 312.23(a)(5). 
(g) Will ensure that all associates, colleagues, and employees assisting in the 
conduct of the study(ies) are informed about their obligations in meeting the above 
commitments.  
 
Commitment 
 
Han Xu, M.D., Ph.D., FAPCR, Sponsor-Investigator 
 
A commitment by the sponsor-investigator that I:  
(a) Will conduct the study (IND 172259) in accordance with the relevant, current 
protocol(s) and will only make changes in a protocol after notifying the sponsor, 
except when necessary to protect the safety, the rights, or welfare of subjects.  
(b) Will comply with all requirements regarding the obligations of clinical investigators 
and all other pertinent requirements in this part.  
(c) Will personally conduct or supervise the described investigation(s).   
(d) Will inform any potential subjects that the drugs are being used for investigational purposes 
and will ensure that the requirements relating to obtaining informed consent (21 CFR part 50) 
and institutional review board review and approval (21 CFR part 56) are met;  
(e) Will report to the sponsor (Han Xu, M.D. Ph.D., FAPCR) adverse experiences that 
occur in the course of the investigation(s) in accordance with § 312.64.   
(f) Have read and understands the information in the investigator's brochure, 
including the potential risks and side effects of the drug.   
21 CFR 312.55(a) 
Han Xu, Sponsor-Investigator, need not give an investigator brochure containing the 
information described in § 312.23(a)(5). 
(g) Will ensure that all associates, colleagues, and employees assisting in the conduct 
of the clinical study (IND 172259) are informed about their obligations in meeting the 
above commitments.  
 

12 
 
21 CFR 312.53(c)(1) 
(vii) A commitment by the investigator that, for an investigation subject to an institutional 
review requirement under part 56, an IRB that complies with the requirements of that part will 
be responsible for the initial and continuing review and approval of the clinical investigation 
and that the investigator will promptly report to the IRB all changes in the research activity 
and all unanticipated problems involving risks to human subjects or others, and will not make 
any changes in the research without IRB approval, except where necessary to eliminate 
apparent immediate hazards to the human subjects.  
 
Commitment 
 
Han Xu, M.D., Ph.D., FAPCR, Sponsor-Investigator 
 
It is my commitment that our Institutional Review Board (IRB) (IRB00009424) that 
complies with the requirements set forth in part 56 will be responsible for the initial 
and continuing review and approval of each of the studies in my proposed clinical 
investigation and that the sponsor-investigator (me i.e. Han Xu, M.D., Ph.D.) will 
report to our IRB (IRB00009424) the proposed changes in my research activity in 
accordance with the requirements of part 56.  
 
(e) The method for determining the dose(s) to be administered, the planned maximum dosage, 
and the duration of individual patient exposure to the drug.  
 
➢ The method for determining the single dose to be administered:  
⚫ 1 Dose i.e., 1 ml - 0.05 mg CEA protein antigen like as following:  
https://www.sigmaaldrich.com/US/en/product/mm/219369  
Millipore-Sigma CEA Antigen Protein  
Product name: Carcinoembryonic Antigen, Human Colon Adenocarcinoma Cell Line  
Pack Size: 0.1 mg  
Product Number: 219369  
Catalogue No.: D44022  
Brand: Millipore  
Company: Sigma-Aldrich Inc.  
 Add 2 mL distilled water into above 0.1 mg CEA protein antigen    
 Before 5 minutes for the percutaneous route with the multiple puncture device, 
above biologic 1ml - 0.05 mg CEA will be added into following biologic BCG:  
⚫ 1 Dose i.e., 50 mg wet weight organism i.e., 1 Intact Vial of lyophilized powder 
like as following:  
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.  
 
➢ The planned maximum dosage: 
⚫ 1 Dose i.e., 1 ml - 0.05 mg CEA protein antigen like as following:  
https://www.sigmaaldrich.com/US/en/product/mm/219369  
Millipore-Sigma CEA Antigen Protein  
Product name: Carcinoembryonic Antigen, Human Colon Adenocarcinoma Cell Line  
Pack Size: 0.1 mg  
Product Number: 219369  
Catalogue No.: D44022  
Brand: Millipore  
Company: Sigma-Aldrich Inc.  
 Add 2 mL distilled water into above 0.1 mg CEA protein antigen    

13 
 
 Before 5 minutes for the percutaneous route with the multiple puncture device, 
above biologic 1 ml - 0.05 mg will be added into following biologic:  
⚫ 1 Dose i.e., 50 mg wet weight organism i.e., 1 Intact Vial of lyophilized powder 
like as following:  
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.  
Active Ingredient(s) and Strength(s) like as following:  
BCG VACCINE contains live bacteria. BCG VACCINE for percutaneous use is 
an attenuated, live culture preparation of the Bacillus of Calmette and Guerin 
(BCG) strain of Mycobacterium bovis. The TICE® strain used in this BCG 
VACCINE preparation. The TICE® BCG organism is grown for preparation of 
freeze-dried cake.  
✓ Bacillus of Calmette and Guerin (BCG) strain of Mycobacterium bovis  
✓ 1 to 8 × 10^8 colony forming units (CFU) of BCG (equivalent to approximately 
50 mg wet weight)  
✓ Merck TICE® BCG organism 50 MG wet weight  
 
➢ The duration of individual patient exposure to the drug: 4-weeks = 28-days 
 
➢ Duration: Our trial duration will be 4-week duration.  
 
(f) A description of the observations and measurements to be made to fulfill the objectives of the study.  
 
➢ The observations and measurements to be made to fulfill the objectives of the study:  
 Positive testing CEA by blood-drawing.  
 TB negative participant is negative IGRA blood test with TB antigens.  
 Positive IGRA blood test with CEA protein antigen after 21 days of mix dosage  
 IGRA blood test with TB antigens will be positive after the percutaneous use 3 weeks 
of the biological product mix dosage.  
 
➢ Endpoint: Positive IGRA blood test with CEA protein antigen after percutaneous use 21 days.  
Rectal Cancer without growth or metastasis 
 
(g) A description of clinical procedures, laboratory tests, or other measures to be taken to 
monitor the effects of the drug in human subjects and to minimize risk.  
 
➢ Positive IGRA blood test with CEA protein antigen after percutaneous use 21 days.   
➢ BCG should not be given to individuals previously infected with M. tuberculosis. A person given the 
IGRA blood test with TB antigens. The TB positive is the positive IGRA blood test with TB antigens.   
➢ BCG can activate the human antigen presenting cells (APCs) to treat CEA target protein 
antigen into small peptide fragments and to kill CEA positive rectal cancer cells in vivo.  
 
The clinical procedures, laboratory tests, or other measures to be taken to monitor the effects of 
the biological product mix in human subjects and to minimize risk like as following:  
 
➢ The clinical procedures to be taken to minimize risk: 
✓ To take the percutaneous use can minimize risk.  
✓ 1 doses of the biological product, CEA protein antigen add into 1 dose of the biological product, 
BCG VACCINE and mix above them before 5 minutes to take the percutaneous use.  
✓ BCG can activate the human antigen presenting cells (APCs) to treat CEA target protein 
antigen into small peptide fragments and to kill CEA positive rectal cancer cells in vivo.  
 

14 
 
➢ The clinical and laboratory tests to be taken to monitor the effects of the biological 
product mix in human subjects:  
✓ Positive testing CEA by blood-drawing  
✓ Negative IGRA blood test with TB antigens  
✓ Positive IGRA blood test with CEA protein antigen after 21 days of mix dosage   
✓ Positive IGRA blood test with TB antigens after the percutaneous use 3 weeks of the 
biological product mix dosage  
 
➢ The clinical and laboratory tests to be taken to minimize risk:  
➢ The risk exclusions like as following:   
 Pregnant 
 Thrombosis 
 Allergy  
 TB participant is positive IGRA blood test with TB antigens.  
 Symptoms of rectal cancer   
 Metastasis of rectal cancer   
 Evidence of critical illness  
 
21 CFR 312.10(a) 
A sponsor may request FDA to waive applicable requirement under this part. A waiver request may 
be submitted either in an IND or in an information amendment to an IND.  
[21 CFR 312.10(a)(3)]  
Other information justifying a waiver.  
 
According to 21 CFR 312.10(a), the sponsor (Han Xu, M.D., Ph.D., FAPCR) needs to request FDA to 
waive applicable requirement under this part which means 21 CFR Part 312. Therefore, my 
investigation must waive the requirements of 21 CFR 312.53(c). In particular, my investigation must 
waive the requirements of 21 CFR 312.53(c)(1). Also, my clinical investigation must waive the 
requirements of 21 CFR §312.305 (c)(1) and 21 CFR §312.305 (c)(3). Although I am not a licensed 
physician, I still can be a qualified sponsor-investigator for my IND Phase I clinical investigation. 
 
21 CFR 312.53(c)(1)(vi)(d) 
Will inform any potential subjects that the drugs are being used for investigational purposes and 
will ensure that the requirements relating to obtaining informed consent (21 CFR part 50) and 
institutional review board review and approval (21 CFR part 56) are met; 
 
I write the statement with respect to each clinical study involving human subjects that it either will be 
conducted in compliance with the institutional review board regulations in part 56 or will not be subject to 
the regulations under §56.104 or §56.105; and that it either will be conducted in compliance with the 
informed consent regulations in part 50 or will not be subject to the regulations under §50.23 and §50.24.  
 
21 CFR 312.53(c)(1)(vii)  
A commitment by the investigator that, for an investigation subject to an institutional review 
requirement under part 56, an IRB that complies with the requirements of that part will be 
responsible for the initial and continuing review and approval of the clinical investigation and that 
the investigator will promptly report to the IRB all changes in the research activity and all 
unanticipated problems involving risks to human subjects or others, and will not make any changes 
in the research without IRB approval, except where necessary to eliminate apparent immediate 
hazards to the human subjects. 
 

15 
 
It is my commitment that our Institutional Review Board (IRB) (IRB00009424) that complies with 
the requirements set forth in part 56 will be responsible for the initial and continuing review and 
approval of each of the studies in my proposed clinical investigation and that the sponsor-
investigator (me i.e. Han Xu, M.D., Ph.D.) will report to our IRB (IRB00009424) the proposed changes 
in my research activity in accordance with the requirements of part 56.  
 
To minimize potential bias resulting from orally verbal voice administration of assessments, the 
sponsor (Han Xu, M.D., Ph.D., FAPCR) will consider using automated virtual interviewers to 
administer the assessments remotely. According to similar principles, the formal pre-IND review will 
be conducted in the format -- written response only (WRO) by email. 
 
Han Xu, M.D., Ph.D., FAPCR, Sponsor-Investigator, IRB Chair, Medical Director  
Health Care Provider - Individual (NPI - 1831468511)  
Health Care Provider - Clinical Ethicist (Code - 174V00000X)  
Health Care Provider - Case Manager/Care Coordinator (Code - 171M00000X)  
Health Care Provider - Internal Medicine (Code - 207R00000X)  
Health Care Provider - Clinical Pharmacology (Code - 208U00000X)  
Health Care Provider - Research Study Specialist (Code - 1744R1102X)  
Health Care Provider - Research Study Abstracter/Coder (Code - 1744R1103X)  
Health Care Provider - Pharmacotherapy Pharmacist (Code - 1835P1200X)  
Health Care Provider - Pharmacist - Clinical Pharmacy Specialist (Code - 1835P0018X)  
Medicine Invention Design Incorporation (MIDI) IRB #1 (IRB00009424)  
IRB Chair (IRB00009424)  
Medicine Invention Design Incorporation (IORG0007849)  
Medicine Invention Design Incorporation (FWA00015357)  
Human Protections Administrator (FWA00015357)  
Human Subjects Administrator (FWA00015357)  
CAQH Approved Maryland State License (D11379922)  
Medicine Invention Design, Inc. (D11379922)  
Medical Director (D11379922)  
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)  
Health Care Provider - Case Management Agency (Code - 251B00000X)  
Health Care Provider - Institutional Pharmacy (Code - 3336I0012X)  
Health Care Provider - Specialty Pharmacy (Code - 3336S0011X)  
Health Care Provider - Managed Care Organization Pharmacy (Code - 3336M0003X)  
Health Care Provider - Mail Order Pharmacy (Code - 3336M0002X)  
Health Care Provider - Medical Specialty Clinic/Center (Code - 261QM2500X)  
Health Care Provider - Multi-Specialty Clinic/Center (Code - 261QM1300X)  
Health Care Provider - Multi-Specialty Group - (Code - 193200000X)  
Health Care Provider - Pharmacist - Clinical Pharmacy Specialist (Code - 1835P0018X)  
 
HAN XU 
 
Mail: 5545 Burnside Drive, Rockville, MD 20853  
Call: 301-222-7143  
Fax: 866-458-0099  
E-mail: hanxumdphd@midinc.us