Thymosin Alpha-1 for irAE Secondary to ICIs

NCT06178146 | Unknown Phase 4

• 1 other identifier: ZAD-irAE
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

IrAE

Keywords

immune-related adverse event; thymosin alpha 1

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• ≤G1 rate

  up to 8 weeks

• Median relieving time

  8 weeks

• The total dose of corticosteroid

  8 weeks

Study Arms (2)

Tα-1 group

EXPERIMENTAL

Subcutaneous injection with 1.6mg Thymosin alpha 1 in combination with the conventional therapy

Drug: Thymosin Alpha1; Drug: Immunosuppressant

Control group

ACTIVE COMPARATOR

Conventional therapy includes corticosteroids and other immunosuppressants according to CSCO guidelines.

Drug: Immunosuppressant

Interventions

Thymosin Alpha1 DRUG

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.

Also known as: thymalfasin

Tα-1 group

Immunosuppressant DRUG

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.

Also known as: Prednisone, Cortisone, Mycophenolate Mofetil, Tacrolimus

Control group; Tα-1 group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jun Wang: lead

Study Sites (1)

The first affiliated hospital of Shandong First Medical University

Jinan, Shandong, 250014, China

RECRUITING

Related Publications (6)

• Serafino A, Pierimarchi P, Pica F, Andreola F, Gaziano R, Moroni N, Zonfrillo M, Sinibaldi-Vallebona P, Garaci E. Thymosin alpha1 as a stimulatory agent of innate cell-mediated immune response. Ann N Y Acad Sci. 2012 Oct;1270:13-20. doi: 10.1111/j.1749-6632.2012.06707.x.

  PMID: 23050812 RESULT

• Romani L, Oikonomou V, Moretti S, Iannitti RG, D'Adamo MC, Villella VR, Pariano M, Sforna L, Borghi M, Bellet MM, Fallarino F, Pallotta MT, Servillo G, Ferrari E, Puccetti P, Kroemer G, Pessia M, Maiuri L, Goldstein AL, Garaci E. Thymosin alpha1 represents a potential potent single-molecule-based therapy for cystic fibrosis. Nat Med. 2017 May;23(5):590-600. doi: 10.1038/nm.4305. Epub 2017 Apr 10.

  PMID: 28394330 RESULT

• Renga G, Bellet MM, Pariano M, Gargaro M, Stincardini C, D'Onofrio F, Mosci P, Brancorsini S, Bartoli A, Goldstein AL, Garaci E, Romani L, Costantini C. Thymosin alpha1 protects from CTLA-4 intestinal immunopathology. Life Sci Alliance. 2020 Aug 14;3(10):e202000662. doi: 10.26508/lsa.202000662. Print 2020 Oct.

  PMID: 32817121 RESULT

• Wu J, Zhou L, Liu J, Ma G, Kou Q, He Z, Chen J, Ou-Yang B, Chen M, Li Y, Wu X, Gu B, Chen L, Zou Z, Qiang X, Chen Y, Lin A, Zhang G, Guan X. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Crit Care. 2013 Jan 17;17(1):R8. doi: 10.1186/cc11932.

  PMID: 23327199 RESULT

• Liu J, Shen Y, Wen Z, Xu Q, Wu Z, Feng H, Li Z, Dong X, Huang S, Guo J, Zhang L, Chen Y, Li W, Zhu W, Du H, Liu Y, Wang T, Chen L, Teboul JL, Annane D, Chen D. Efficacy of Thymosin Alpha 1 in the Treatment of COVID-19: A Multicenter Cohort Study. Front Immunol. 2021 Aug 2;12:673693. doi: 10.3389/fimmu.2021.673693. eCollection 2021.

  PMID: 34408744 RESULT

• Liu F, Qiu B, Xi Y, Luo Y, Luo Q, Wu Y, Chen N, Zhou R, Guo J, Wu Q, Xiong M, Liu H. Efficacy of Thymosin alpha1 in Management of Radiation Pneumonitis in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Concurrent Chemoradiotherapy: A Phase 2 Clinical Trial (GASTO-1043). Int J Radiat Oncol Biol Phys. 2022 Nov 1;114(3):433-443. doi: 10.1016/j.ijrobp.2022.07.009. Epub 2022 Jul 21.

  PMID: 35870709 RESULT

MeSH Terms

Interventions

Thymalfasin; Immunosuppressive Agents; Prednisone; Cortisone; Mycophenolic Acid; Tacrolimus

Intervention Hierarchy (Ancestors)

Thymosin; Thymus Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnenes; 17-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones

Study Officials

• Jun Wang, Professor

  Shandong First Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Wang, Professor

CONTACT

0531-89269221; ggjun2005@126.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: December 3, 2023
• First Posted: December 20, 2023
• Study Start: September 1, 2023
• Primary Completion: November 1, 2024
• Study Completion: April 1, 2025
• Last Updated: December 20, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)