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The purpose of this prospective pilot clinical study is to evaluate the safety and immunostimulatory effect of intramuscularly administrations of autologous total IgG (autologous total IgG therapy) in healthy subjects and patients with advanced solid tumor (non-small cell lung cancer, stomach cancer, colon cancer, ovarian cancer, breast cancer, pancreatic cancer, biliary cancer, melanoma, renal cell carcinoma etc.). In addition, antitumor effect of intramuscularly administrations of autologous total IgG in patients with advanced solid tumor will be also evaluated.
After providing informed consent, study participants will be assessed for study eligibility at the screening visit. At screening visit (week -4), venous blood (320~400 mL) will be sampled using a double blood bag containing anticoagulant. Autologous plasma will be separated from the venous blood by centrifugation. During the 4 weeks of screening period, autologous total IgG (purity ≥97%) will be aseptically purified from the autologous plasma by chromatography using Protein A. Participants will receive the 8 intramuscular injections of autologous total IgG, twice a week for 4 weeks from baseline (week 0).
The investigators will evaluate the safety and immunostimulatory effect of intervention of this study by analyzing side effects, serum concentrations of immunological parameters (immunoglobulin, cytokine, etc.), and lymphocyte fraction by flow cytometry analysis of peripheral blood mononuclear cells.
[Part A) Autologous total IgG therapy in healthy subjects] The duration of this clinical study in healthy subjects is 16 weeks from the screening visit. A 4-week screening period will be followed by a 4-week intervention period and an 8-week follow-up period.
[Part B) Autologous total IgG therapy in patients with advanced solid tumor] The duration of this clinical study in patients with advanced solid tumor is 12 weeks from the screening visit. A 4-week screening period will be followed by a 4-week intervention period and a 4-week follow-up period(1 cycle).
If the patients agree to participate in additional long-term repeated study interventions at the end of 1st cycle of visit, patients will receive repeated study interventions in same the schedule up to week 44 (maximum 4 cycles). At the end of each cycle, antitumor effect will be evaluated by serum tumor marker concentrations, anatomical imaging, and Response Evaluation Criteria in solid tumors (RECIST ver. 1.1).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A) Healthy subjects | Experimental | Part A) Autologous total IgG 50mg will be administered to the healthy subjects by intramuscular injections, twice a week for 4 weeks (total 8 injections). |
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| Part B) Advanced solid tumor | Experimental | Part B) Autologous total IgG 50mg will be administered to the patients with advanced solid tumor by intramuscular injection, twice a week for 4 weeks (total 8 injections). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Part A) Healthy subjects | Biological | Part A) Autologous total IgG 50mg will be administered to the healthy subjects by intramuscular injections, twice a week for 4 weeks (total 8 injections). |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with severe adverse events (AEs), serious adverse events (SAEs), treatment-related AEs, deaths, or discontinuation of study intervention due to AEs in healthy subjects | From baseline to week 12 | |
| Number of participants with severe adverse events (AEs), serious adverse events (SAEs), treatment-related AEs, deaths, or discontinuation of study intervention due to AEs in patients with advanced solid tumor | From baseline to week 8 and through study completion, an average of 3 year |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with abnormal serum chemistry results and blood test results due to clinical study in healthy subjects | From baseline to week 12 | |
| Serum concentrations of immunological parameters (immunoglobulin, cytokine, etc.) in healthy subjects |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dong-Ho Nahm | Ajou University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ajou university hosiptal | Suwon | Gyeong-gi Do | 16499 | South Korea |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35665739 | Derived | Kwon B, Yang SJ, Cho SM, Kim ME, Nahm DH. Intramuscular administration of autologous total immunoglobulin G induces immunomodulatory effects on T cells in healthy human subjects: An open-labeled prospective single-arm trial. Medicine (Baltimore). 2022 Jun 3;101(22):e29486. doi: 10.1097/MD.0000000000029486. |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
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Intramuscularly administrations of autologous total IgG in healthy subjects and patients with advanced solid tumor
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| Part B) Advanced solid tumor | Biological | Part B) Autologous total IgG 50mg will be administered to the patients with advanced solid tumor by intramuscular injection, twice a week for 4 weeks (total 8 injections). |
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| From baseline to week 12 |
| Lymphocyte fraction by flow cytometry analysis of peripheral blood mononuclear cells in healthy subjects | From baseline to week 12 |
| Levels of cytokines secreted from peripheral blood cells in healthy subjects | From baseline to week 12 |
| Quality of life (5-level EuroQoL Group's 5-dimension; EQ-5D-5L) in healthy subjects | The 5-level EuroQoL Group's 5-dimension (EQ-5D-5L) consists of 2 parts: the descriptive system and the EQ visual analogue scale (VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels of perceived problems: no problems, slight problems, moderate problems, severe problems, and unable to/extreme problems. In addition, the EQ-5D-5L include an EQ-VAS where the endpoints are labeled on a scale from 0 (worst imaginable health) to 100 (best imaginable health). | From baseline to week 12 |
| Subjective index of pain and fatigue (Visual Analogue Scale; VAS, Numeral Rating Scale; NRS) in healthy subjects | The 100-mm Visual Analogue Scale (VAS) ranges from 0 (absent) to 10 (worst imaginable). The 11-point Numerical Rating Scale (NRS) ranges from 0 (absent) to 10 (worst imaginable). | From baseline to week 12 |
| Number of participants with abnormal serum chemistry results and blood test results due to clinical study in patients with advanced solid tumor | From baseline to week 8 and through study completion, an average of 3 year |
| Serum concentrations of immunological parameters (immunoglobulin, cytokine, etc.) in patients with advanced solid tumor | From baseline to week 8 and through study completion, an average of 3 year |
| Lymphocyte fraction by flow cytometry analysis of peripheral blood mononuclear cells in patients with advanced solid tumor | From baseline to week 8 and through study completion, an average of 3 year |
| Levels of cytokines secreted from peripheral blood cells in patients with advanced solid tumor | From baseline to week 8 and through study completion, an average of 3 year |
| Objective response rate (ORR) in patients with advanced solid tumor | From baseline to week 8 and through study completion, an average of 3 year |
| Disease control rate (DCR) in patients with advanced solid tumor | From baseline to week 8 and through study completion, an average of 3 year |
| Duration of response (DOR) in patients with advanced solid tumor | From baseline to week 8 and through study completion, an average of 3 year |
| Progression-free survival (PFS) in patients with advanced solid tumor | From baseline to week 8 and through study completion, an average of 3 year |
| Overall survival (OS) in patients with advanced solid tumor | From baseline to week 8 and through study completion, an average of 3 year |
| The tumor marker concentrations in patients with advanced solid tumor | From baseline to week 8 and through study completion, an average of 3 year |
| Quality of life (5-level EuroQoL Group's 5-dimension; EQ-5D-5L) in patients with advanced solid tumor | The 5-level EuroQoL Group's 5-dimension (EQ-5D-5L) consists of 2 parts: the descriptive system and the EQ visual analogue scale (VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels of perceived problems: no problems, slight problems, moderate problems, severe problems, and unable to/extreme problems. In addition, the EQ-5D-5L include an EQ-VAS where the endpoints are labeled on a scale from 0 (worst imaginable health) to 100 (best imaginable health). | From baseline to week 8 and through study completion, an average of 3 year |
| Subjective index of pain and fatigue (Visual Analogue Scale; VAS, Numeral Rating Scale; NRS) in patients with advanced solid tumor | The 100-mm Visual Analogue Scale (VAS) ranges from 0 (absent) to 10 (worst imaginable). The 11-point Numerical Rating Scale (NRS) ranges from 0 (absent) to 10 (worst imaginable). | From baseline to week 8 and through study completion, an average of 3 year |