Thymosin Alpha-1 for irAE Secondary to ICIs

Study Overview
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Brief Summary
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Thymosin alpha-1 (Tα-1) has shown clinical benefits in patients whose immune functions are severely compromised or ineffective. Therefore, this study is attempted to explore whether Tα-1 could be used as a therapeutic option for the treatment of immune-related adverse events (irAEs).

Official Title
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A Prospective, Open, Randomized Controlled Stage II Trial Investigating the Efficacy and Safety of Thymosin Alpha-1 in Treating Moderate to Severe Immune-related Adverse Events

Conditions
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IrAE

Intervention / Treatment
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* Drug: Thymosin Alpha1
* Drug: Immunosuppressant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who are males or females, aged 18 to 75 years; Subjects who are willing to sign the informed consent forms and receive follow-up visits; Subjects who are cytologically or histologically diagnosed with malignant solid tumors, including but not limited to genitourinary, gynecological, lung, liver, gastrointestinal tumors and melanoma; Subjects with malignant solid tumors who have developed irAEs within 6 months of immune checkpoint inhibitor therapy (CTLA-4, PD-1 and/or PD-L1). The immune checkpoint inhibitors can be used alone, or combined with chemotherapy drugs or other ICIs; Subjects with Grade 2 to 4 skin toxicity, enteritis, pneumonia and hepatitis secondary to ICIs according to CTCAE V5.0 and CSCO guidelines Subjects with sufficient bone marrow functions and meet the following requirements: (1) Hemoglobin level ≥ 90 g/L (2) Neutrophil count ≥ 1.0×10^9/L (3) Lymphocyte count ≥ 0.5×10^9/L (4) Platelet count ≥75×10^9/L (5) PT, PTT, INR≤1.5 times ULN 7. Subjects with sufficient liver functions: Child-Pugh A and B; 8. Subjects with sufficient renal function: the estimated clearance rate calculated by the Cockroft-Gault formula is ≥40mL/min; 9. Suitable pregnant women who need to take effective contraceptive measures; Exclusion Criteria: Subjects who have ever immune-related adverse events due to ICI treatment; Subjects who are diagnosed with immunodeficiency disease or are receiving systemic immunosuppressive therapy; Subjects who have skin damage, liver damage, lung damage, etc. caused by the progression of malignant tumors; Subjects who have the thromboembolic disease, biliary tract compression, perfusion injury, opportunistic infection, and liver injury caused by non-ICI drug reactions; Subjects who have abnormal laboratory indicators caused by hepatotropic viruses (such as HAV, HBC, HCV) and non-hepatotropic viruses (such as Epstein-Barr virus, cytomegalovirus, and herpes simplex virus); Subjects who are diagnosed with infectious colitis (e.g., caused by infections such as bacteria, Clostridium difficile, virus, fungus, parasite, etc.); Subjects who suffer from autoimmune diseases, including but not limited to autoimmune hepatitis, primary cholangitis, primary sclerosing cholangitis, rheumatoid arthritis, vitiligo, psoriasis, Crohn's disease, type I diabetes, Grave's disease, etc.; Subjects who suffer from other respiratory diseases with clear etiology, including malignant pulmonary infiltration, active infection, alternative systemic pulmonary toxicity or radiation pneumonitis; Subjects with any other infectious diseases of grade 3 and above; Subjects who have received and used thymosin products or other immunomodulators before enrollment; Subjects who are allergic to thymosin products; Pregnant or breastfeeding women; Subjects who have any known bacterial, fungal or viral infections that may affect their safety or study compliance as deemed by the Investigator within 2 weeks before enrollment; Subjects who have any health conditions that may prevent them from participating in and complying with the procedures related to the study as deemed by the Investigator, including additional laboratory abnormalities or mental illness.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tα-1 group<br>Subcutaneous injection with 1.6mg Thymosin alpha 1 in combination with the conventional therapy | Drug: Thymosin Alpha1<br>* Based on the conventional treatment, subcutaneous injection of Tα-1 (1.6 mg, qd) in Week 1; and in Week 2, subcutaneous injection of thymalfasin 1.6 mg, 3 times a week, followed by twice a week for 1 month since Week 3.<br>* Other names: thymalfasin;Drug: Immunosuppressant<br>* Grade 2 irAEs: corticosteroid alone Grade 3 and above irAEs: corticosteroids combined with other immunosuppressants Steroid-refractory irAE: After 48-72 hours of systemic steroid therapy, the symptoms do not improve or worsen, and the second-line immunosuppressant therapy is adopted.<br>* Other names: Tacrolimus;|
| Active Comparator: Control group<br>Conventional therapy includes corticosteroids and other immunosuppressants according to CSCO guidelines. | Drug: Immunosuppressant<br>* Grade 2 irAEs: corticosteroid alone Grade 3 and above irAEs: corticosteroids combined with other immunosuppressants Steroid-refractory irAE: After 48-72 hours of systemic steroid therapy, the symptoms do not improve or worsen, and the second-line immunosuppressant therapy is adopted.<br>* Other names: Tacrolimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptoms relieving rate | The proportion of immune-related adverse events reduced by at least 1 grade within 1 week after the first injection of thymalfasin. | within one week after the first injection of thymalfasin. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ≤G1 rate | The proportion of total immune-related adverse events reduced to ≤ Grade 1 within 2, 4, 6 and 8 weeks after the first injection of thymalfasin; | up to 8 weeks | 
| Median relieving time | The median time for an immune-related adverse event reduced to ≤ Grade 1 | 8 weeks | 
| The total dose of corticosteroid | The total dose of corticosteroids used during treatment, the duration and the proportion of intravenous infusion (IV) | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immune-related adverse event, thymosin alpha 1