A Phase I/II Trial of VUM02 Injection for Steroid-refractory Acute Graft-versus-host Disease (SR-aGvHD) Treatment

NCT06677255 | Not Yet Recruiting Phase 1

• 2 other identifiers: VUM02-GVHD-01China NMPA
• Study Type: interventional
• Target: 149
• Locations: 1 country
• Sites: 1

Brief Summary

It is a phase I/II clinical study to evaluate the safety, tolerability and preliminary efficacy of VUM02 Injection in patients with acute graft-versus-host disease (aGvHD) who have failed systemic steroid therapy. VUM02 Injection (human umbilical cord-derived mesenchymal stromal /stem cells, hUC-MSC) is an off-the-shelf allogeneic cell therapy product comprising culture-expanded mesenchymal stromal /stem cells derived from the human umbilical cord tissue. The product is cryopreserved with the cell concentration of 5 x 10\^6 cells/mL. Patients with grade II to IV aGvHD who have failed systemic steroid therapy (i.e. patients with steroid-refractory aGvHD (SR-aGvHD)), will be recruited into this study. This study consists of two phases, a dose-escalation phase (phase I) and a dose-expansion phase (phase II).

Conditions

Steroid-refractory Acute Graft-versus-host Disease

Keywords

acute graft-versus-host disease; Mesenchymal stromal /stem cells; SR-aGvHD; VUM02 Injection

Outcome Measures

Primary Outcomes (2)

• Occurrence of Dose-limiting toxicity (DLT) events (in Phase Ia and Ib )

  Occurrence of Dose-limiting toxicity (DLT) events during 14 days after single administration in phase Ia, and from the first dosing to 28 days after the last dosing in phase Ib. Dose-limiting toxicity (DLT) events is defined as cell therapy-related adverse events (AEs) of grade 3 and above as assessed by CTCAE (V5.0).

  14 days, 28 days after the last dosing

• Overall response rate (ORR) at day 28 post initiation of therapy (in Phase II)

  ORR was defined as the percentage of participants who had achieved overall response. Overall response was defined as complete response (CR) plus partial response (PR) according to aGVHD response criteria. CR was defined as resolution of aGVHD in all involved organs. PR was defined as organ improvement of at least 1 stage without worsening of any other organ by day 28 after the first dosing in phase II

  28 days after the first dosing

Secondary Outcomes (10)

• Incidence and severity of cell therapy-related adverse events (AEs) (in phase Ia, Ib and II)

  14 days, 28 days,or 180 days after the first dosing

• Immunogenicity evaluation (in Phase Ib and Phase II)

  Before administration, and 8, 15, 22, 28, and 56 days after first dosing

• Overall response rate (ORR) and Complete response rate (CRR) and Durable complete response rate (Durable-CRR) (in Phase Ib)

  28 and 56 days after the first dosing

• Overall response rate (ORR), Complete response rate (CRR) and Durable complete response rate (Durable-CRR) (in Phase II)

  28 and 56 days after the first dosing

• Time to complete response (CR) and Time to partial response (PR) (in Phase II)

  100 days after the first dosing

Other Outcomes (2)

• Levels of TNFRI, IL-2Rα, REG3 and ST2 (Phase Ib and Phase II)

  Before administration, and 15, 28, 56, and 100 days after the first dosing

• Levels of Th17 and Treg (Phase Ib and Phase II)

  Before administration, and 15, 28, 56, and 100 days after the first dosing

Study Arms (2)

VUM02 Injection (UC-MSCs)+BAT

EXPERIMENTAL

In Phase I, subjects receive 3 sequential IV dose levels of VUM02 Injection (UC-MSCs): * Phase Ia, single-dose escalation: 1x10\^6 cells/kg, or, 2x10\^6 cells/kg, or, 3x10\^6 cells/kg, single dose; * Phase Ib, multiple-dose escalation: 1x10\^6 cells/kg, or, 2x10\^6 cells/kg, or, 3x10\^6 cells/kg, twice a week for 4 weeks, a total of 8 times. Phase II is the dose-expansion study: Two dose levels will be selected by the investigator and the sponsor according to the results of the Phase 1b study, with IV of VUM02 Injection twice a week for 4 consecutive weeks for a total of 8 doses. * Study group 1: VUM02-dose 1 + BAT * Study group 2: VUM02-dose 2 + BAT

Drug: VUM02 Injection (UC-MSCs)+BAT

The control group with Best available therapy

OTHER

It is the control group of Phase II study to receive only the best available therapy (BAT). According to BAT scheme, the drug regimen is determined by PI based on the condition of the patients.

Other: The control group with Best Available Therapy (BAT)

Interventions

VUM02 Injection (UC-MSCs)+BAT DRUG

The dose-escalation phase (phase I): Single dose escalation Phase 1a study: 3 dose levels of a single IV infusion; Multiple dose escalation Phase 1b study: 3 dose levels of twice weekly for 4 consecutive week. The dose-expansion phase (phase II): -Two dose groups will be selected by the investigator and the sponsor based on the results of the Phase 1b study, twice a week for 4 consecutive weeks for a total of 8 doses.

VUM02 Injection (UC-MSCs)+BAT

The control group with Best Available Therapy (BAT) OTHER

According to BAT scheme, the drug administration is determined by PI according to the condition of the patients.

Also known as: Control group

The control group with Best available therapy

Eligibility Criteria

• Age: 14 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet all of the following criteria to be eligible for this trial:
• Subjects aged 14-70 years (inclusive), male or female;
• Subjects who undergone allogeneic hematopoietic stem cell transplantation as indicated for hematological malignant disease, developed with grade II to IV aGvHD and failed standard first-line steroid therapy (that is, SR-aGvHD); 1) Definition of standard first-line steroid /glucocorticoid therapy: 1 mg/kg/day or 2 mg/kg/day of Methylprednisolone, or equivalent doses of steroids; 2) According to Thomas' Hematopoietic Cell Transplantation: Stem Cell Transplantation (5th edition), subjects who meet one of the following criteria are considered to have failed the standard first-line steroid /glucocorticoid therapy:
• a. Steroid resistance: Progression of aGvHD at Day 3 of first-line steroid therapy, or no improvement in aGvHD at Day 7, or incomplete remission of aGvHD at Day 14;
• b. Steroid dependence: failure to taper first-line steroid therapy or reactivation of aGvHD during taper;
• Investigator assessment: Expected survival ≥ 3 months;
• Clinical manifestations of aGvHD are rash and/or persistent nausea, vomiting, and/or diarrhea and/or cholestasis. For these clinical manifestations, other etiologies such as drug rash, intestinal infection, or hepatotoxicity syndrome have been ruled out;
• Subjects will be required to receive the investigational product within 3 days of enrollment;
• Subjects must give informed consent to the study prior to enrollment, with the subject himself/herself, or, the subject himself/herself and his/her legal guardian (only for subjects \<18 years of age), voluntarily signing a written informed consent form.

You may not qualify if:

• Patients meeting any of the following criteria are not eligible for this trial:
• Subjects with lung disease who, in the judgment of the investigator, are not appropriate to participate in the study;
• Serum virological examination shows positive results for active hepatitis B (hepatitis B core antibody positive and HBV-DNA in peripheral blood higher than the upper limit of normal), hepatitis C (hepatitis C antibody positive and HCV-RNA higher than the upper limit of normal), Treponema pallidum (TP) antibody or human immunodeficiency virus (HIV) antibody;
• Patients with severe hepatic veno-occlusive disease or sinus veno-occlusive syndrome;
• Subjects who developed aGvHD after donor lymphocyte infusion therapy for recurrence of underlying hematologic malignancies;
• Patients complicated with brain lesion or who, in the judgment of the investigator, present with mental status changes;
• Patients with coagulation dysfunction requiring anticoagulant therapy or antiplatelet therapy;
• Subject's renal function: Creatinine clearance \<30mL/min; creatinine clearance is calculated using the Cockcroft-Gault formula: Ccr(ml/min)=\[(140-age)×body weight(kg)\]/(72×blood creatinine (mg/dL), calculated results × 0.85 for females), and attention should be paid to the unit of creatinine during calculation of creatinine clearance;
• ECOG PS score \> 3;
• Subjects who have evidence within 6 months prior to enrollment that suggests that they have other diseases or their physiological conditions may interfere with the evaluation results of this study, or have serious life-threatening complications, including but not limited to uncontrolled infection, pulmonary hypertension, severe cardiac insufficiency (NYHA Class III and IV), unstable angina pectoris or acute myocardial infarction, refractory hypertension (defined as the simultaneous use of 3 different types of antihypertensive drugs \[one of which is the diuretic\], and blood pressure remains higher than 160/110 mmHg) (subject to the inpatient medical record diagnosis);
• Patients with active malignant solid tumor within 5 years before the study, except radically treated cervical cancer, localized prostate cancer in situ and non-melanoma skin cancer;
• Patients suffering from mental and neurological diseases and unable to correctly express their wishes;
• Patients who have received ≥ 1 therapy for aGvHD other than hormonal and protocol-recommended second-line agents prior to the study (subjects who received prophylactic drugs for aGvHD prior to the study may be included in this study);
• Patients with a known history of severe allergy to blood components or blood products, or to heterologous proteins;
• Breastfeeding women, or female subjects who have plans to become pregnant or donate eggs from the start of the study to the follow-up period, and male subjects (or their partners) who have plans to father a child or donate sperm from the start of the study to the follow-up period and are unwilling to take contraceptive measures;

Sponsors & Collaborators

• Wuhan Optics Valley Vcanbiopharma Co., Ltd.: lead

Study Sites (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

Location

MeSH Terms

Interventions

Control Groups

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Central Study Contacts

Tengyun Dong, Operations Director

CONTACT

+86-27--87002897; dongtengyun@vcanbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2024
• First Posted: November 6, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: November 6, 2024

Record last verified: 2024-11

Locations

CN (1)