HUC-MSC for Treatment of High-risk HPV Infection

Effectiveness and Safety of Human Umbilical Cord Mesenchymal Stem Cells for the Treatment of HPV High-risk Infection

To evaluate the safety and initial effectiveness of human umbilical cord mesenchymal stem cells in HPV clearance.

Study Overview

• Status: Recruiting
• Conditions: Mesenchymal Stem Cells; Human Papillomavirus Viruses
• Intervention / Treatment: Biological: hUC-MSCs; Biological: Saline+albumin

Detailed Description

Cervical cancer is one of the most common malignant tumors of the female reproductive system with the highest incidence. Nearly 99.7% of cervical cancer is caused by HPV infection. Studies have shown that the persistent infection of high-risk human papillomavirus (HR-HPV) is an independent risk factor for cervical cancer which can lead to a 250-fold increased risk of high-grade cervical intraepithelial neoplasia (CIN). In patients with persistent HR-HPV infection for more than 12 months, the risk of diagnosis of high-grade squamous intraepithelial lesions of the cervix by 30 months increased to 21%. In the process of progression from HPV infection to cervical cancer, cervical precancerous lesions, namely intraepithelial neoplasia (CIN), will be experienced. Therefore, effective control of HPV infection, especially the elimination of persistent HR-HPV infection, will greatly reduce the incidence of CIN and cervical cancer. It is an urgent clinical need to actively intervene in patients with persistent infections for more than one year with a clinical significance at present.

Mesenchymal Stem Cells (MSCs) are a class of pluripotent stem cells derived from the mesoderm and ectoderm of early development, which can be easily obtained from a variety of tissue organs, having a strong proliferation and multidirectional differentiation potential in vitro. hUC-MSCs have a great effect on immune regulation and anti-inflammatory properties with a fewer ethical, availability, safety issues and a broader prospect in clinical research and application. At present, many experimental data have proved that MSCs can enhance the clearance of virus by immune cells in vivo, and have a certain application prospect in fighting virus infection. The purpose of this study was to evaluate the safety and therapeutic efficacy of human umbilical cord mesenchymal stem cells (HUC-MSCs) in clearing HPV infection, and to provide clinical basis for HUC-MSCs to clear HPV infection.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jingjing Liu, M.D,.PH.D.; Phone Number: 13795350828; Email: liu.doctor@hotmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200120
      • Recruiting
      • Shanghai Shanghai East Hospital, Tongji University School of Medicine
      • Contact: Fang Li, M.D.,PH.D.; Phone Number: 13801986709; Email: fang_li@tongji.edu.cn
      • Contact: Fang Li, M.D.,PH.D.
      • Contact: Zhongmin Liu, M.D.,PH.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Women aged 25-60 with a sexual history of more than 2 years;
2. Confirmed HPV infection by HPV-24 test;Patients diagnosed with high-risk human papillomavirus (HR-HPV) persistent infection; (note: the HR HPV: HPV 16/18/31/33/35/39/45/51/52/53/56/58/59/66/68; 15 types)
3. The subjects were not participating in other clinical trials at the same time, and had no other anti-HPV drugs or intervention therapy recently;
4. If the pregnancy test is negative and the subjects have fertility potential, they agree to use effective contraception during the study period and within 6 months of completion or termination of the study;
5. Voluntarily participate in and agree to cooperate in accordance with the requirements of the program, and sign the informed consent.

Exclusion Criteria:

1. Women who are preparing for pregnancy, pregnancy or breastfeeding;
2. Pathological diagnosis of high-grade squamous intraepithelial lesion (HSIL) or cervical cancer;
3. Previous HPV vaccinations;
4. A history of severe drug allergies, or allergies to stem cell products or other biologics;
5. Previous cervical site physical therapy or related surgical history;
6. Patients with severe immune dysfunction (such as AIDS, systemic lupus erythematosus and other immune system diseases or history of organ transplantation, malignant tumor chemotherapy history), serious cardiovascular, liver, kidney, nervous, hematopoietic system diseases or malignant tumors, or mental diseases;
7. Recent use of other antiviral drugs, immunosuppressants, immunomodulators or steroid hormones that affect the immune system;
8. Patients with acute genital tract inflammation or pelvic inflammation;
9. Those who have participated in or are participating in clinical trials of other drugs within three months;
10. Other conditions considered inappropriate by the investigator for inclusion in this clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; 1×10^6/Kg UC-MSCs (resuspended in 100 mL normal saline containing 5% albumin) are infused intravenously to the high-risk HPV persistant infected patients at a controlled rate of 60-80 drops/min	Biological: hUC-MSCs; 1×10^6/Kg hUC-MSCs (suspended in 100 mL normal saline containing 5% albumin) are infused intravenously to patients at a controlled rate of 60-80 drops/min.; Other Names: Umbilical Cord Mesenchymal Stem Cells
Placebo Comparator: Control group; Normal saline containing 5% albumins are infused intravenously with an equal volume, similar suspension and appearance package as UC-MSCs to the high-risk HPV persistant infected patients at a controlled rate of 60-80 drops/min	Biological: Saline+albumin; Normal saline containing 5% albumin had a similar suspension and appearance package to hUC-MSCs, but no MSCs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events-The incidence rate of allergic reaction	The allergic reaction rate on the 1st day, 1st week, 4th week, 12th week, and 36th week after the infusion.	1day,1st,4th,12th,and 36th week
The 24 type HPV viral load	HPV24 genotypes test is classified from female genitourinary secretions and exfoliating cells of cervix by fluorescent PCR before the infusion of hUC-MSCs (Any day from 28th to 1st day) and on the 4th week, 12th week, and 36th week after the infusion.	-28th~0day,4th,12th,and 36th week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The percentage of CD3+	The peripheral blood serum of the patients will be collected to detect the percentage（%）of CD3+ before the infusion of hUC-MSCs (Any day from 28th to 1st day) and on the 1st day, 1st week, 4th week, 12th and 36th week after the infusion.	-28th~0day,1day,1st,4th,12th,and 36th week
The percentage of CD4+	The peripheral blood serum of the patients will be collected to detect the percentage（%）of CD4+ before the infusion of hUC-MSCs (Any day from 28th to 1st day) and on the 1st day, 1st week, 4th week, 12th and 36th week after the infusion.	-28th~0day,1day,1st,4th,12th,and 36th week
The percentage of CD8+	The peripheral blood serum of the patients will be collected to detect the percentage（%） of CD8 before the infusion of hUC-MSCs (Any day from 28th to 1st day) and on the 1st day, 1st week, 4th week, 12th and 36th week after the infusion.	-28th~0day,1day,1st,4th,12th,and 36th week
The percentage of CD19+	The peripheral blood serum of the patients will be collected to detect the percentage（%）of CD19+ before the infusion of hUC-MSCs (Any day from 28th to 1st day) and on the 1st day, 1st week, 4th week, 12th and 36th week after the infusion	-28th~0day,1day,1st,4th,12th,and 36th week
The percentage of CD16+/CD56+	The peripheral blood serum of the patients will be collected to detect the percentage（%） of CD16+/CD56+ before the infusion of hUC-MSCs (Any day from 28th to 1st day) and on the 1st day, 1st week, 4th week, 12th and 36th week after the infusion.	-28th~0day,1day,1st,4th,12th,and 36th week
The serum level of IFN-γ	The peripheral blood serum of the patients will be collected to detect the level of IFN-γ (pg/mL) before the infusion of hUC-MSCs (Any day from 28th to 1st day) and on the 1st day, 1st week, 12th week, and 36th week after the infusion.	-28th~0day,1day,1st,4th,12th,and 36th week
The serum level of IL-6	The peripheral blood serum of the patients will be collected to detect the level of IL-6 (pg/mL) before the infusion of hUC-MSCs (Any day from 28th to 1st day) and on the 1st day, 1st week, 4th week,12th week, and 36th week after the infusion.	-28th~0day,1day,1st,4th,12th,and 36th week
The serum level of IL-8	The peripheral blood serum of the patients will be collected to detect the level of IL-8 (pg/mL) before the infusion of hUC-MSCs (Any day from 28th to 1st day) and on the 1st day, 1st week, 4th week,12th week, and 36th week after the infusion.	-28th~0day,1day,1st,4th,12th,and 36th week
The serum level of IL-10	The peripheral blood serum of the patients will be collected to detect the level of IL-10 (pg/mL) before the infusion of hUC-MSCs (Any day from 28th to 1st day) and on the 1st day, 1st week, 4th week,12th week, and 36th week after the infusion.	-28th~0day,1day,1st,4th,12th,and 36th week
The serum level of TNF-α	The peripheral blood serum of the patients will be collected to detect the level of TNF-α (pg/mL) before the infusion of hUC-MSCs (Any day from 28th to 1st day) and on the 1st day, 1st week, 12th week, and 36th week after the infusion.	-28th~0day,1day,1st,4th,12th,and 36th week

Collaborators and Investigators

• Sponsor: Shanghai East Hospital
• Investigators: Principal Investigator: Fang Li, M.D,.PH.D., Shanghai East Hospital, Shanghai Tongji University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): September 10, 2025
• Study Completion (Estimated): September 10, 2026

Study Registration Dates

• First Submitted: August 28, 2024
• First Submitted That Met QC Criteria: September 22, 2024
• First Posted (Actual): September 24, 2024

Study Record Updates

• Last Update Posted (Actual): September 24, 2024
• Last Update Submitted That Met QC Criteria: September 22, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: HPV; hUC-MSC
• Additional Relevant MeSH Terms: Infections
• Other Study ID Numbers: DFSC-2024(CR)-001; HX-2021-007 (Other Grant/Funding Number: Shanghai Shanghai East Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No