Efficacy, Safety, and Pharmacokinetics of Shu Yang IVIG

NCT06089122 | Unknown Phase 3 DMC

• 2 other identifiers: IMUNOFORTEU1111-1298-7059
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

To evaluate the safety, efficacy, and pharmacokinetic properties of Shu Yang intravenous immune globulin in patients with primary immune deficiency aged less than 60 years. The main benefit of IVIG is to help the body fight against a large variety of infections generally associated with morbidity and mortality in patients with primary immunodeficiency diseases, particularly in CVID and XLA. In addition, a decrease in the number of infections, a reduction in medications and hospitalizations, and a better quality of life are expected. Throughout treatment, approximately one-fourth of persons may experience a side effect. These are usually mild or bothersome but not dangerous. Very rarely, more serious side effects like allergic reactions or low blood counts (anemia) can occur. One of the most common side effects is headache. Other side effects include chills, fever, flushing, flu-like muscle pains or joint pains, feeling tired, nausea, vomiting, and rash. For the most part, these reactions typically happen with the first dose of IVIG or because change to a different brand of IVIG. All IVIG products have similar warnings and contraindications, such as the potential for renal failure, thrombotic events, aseptic meningitis, hemolysis, and anaphylactic reactions.

Conditions

Primary Immunodeficiency Disease

Keywords

IVIG; IMUNOFORTE; PID

Outcome Measures

Primary Outcomes (1)

• Primary Efficacy Objective (average of acute serious bacterial infections)

  The incidence of serious bacterial infections (septicemia, meningitis, visceral abscess, osteomyelitis, and pneumonia) within the 1-year follow-up is less than 1.0 per patient/year in the average of the population.

  Between Visit 0 and Final Visit (through study completion, an average of 1 year)

Secondary Outcomes (4)

• Secondary Efficacy Objectives (assessment of the rate of non-serious infections)

  Average incidence of non-serious infections per patient between Visit 0 and Final Visit (through study completion, an average of 1 year), as documented as treatment emergent adverse events (TEAEs);

• Secondary Efficacy Objectives

  Average number of days for treating infections per patient between visit 0 and final visit (through study completion, an average of 1 year), as documented as treatment emergent adverse events (TEAEs);

• Secondary Efficacy Objectives

  Average number of days off from school/work per patient/month, as documented in the patient's diary (through study completion, an average of 1 year);

• Secondary Efficacy Objectives

  Number of days hospitalized per month overall and due to infection, as documented as treatment emergent adverse events - TEAEs (through study completion, an average of 1 year).

Other Outcomes (8)

• Secondary Pharmacokinetic (PK) Objectives

  9 months

• Secondary Pharmacokinetic (PK) Objectives

  28 days

• IgG half-life

  28 days

Study Arms (1)

IVIG

EXPERIMENTAL

Patients with primary immunodeficiency will switch to Shu Yang IVIG and optimize the posology to IgG 300 to 600 mg every 21 or 28 days in a run-in period of 2 to 6 administrations, aiming at keeping the IgG trough levels above 5 g/L. In the one-year test period, the patients will receive the test IVIG at the same dose/intervals of the optimization. However, the IgG trough levels will be monitored every visit, and new adjustments/dose optimization will be performed whenever needed to keep the IgG trough levels above 5g/L.

Biological: IVIG

Interventions

IVIG BIOLOGICAL

Patients with primary immunodeficiency will switch to Shu Yang IVIG and optimize the posology to IgG 300 to 600 mg every 21 or 28 days in a run-in period of 2 to 6 administrations, aiming at keeping the IgG trough levels above 5 g/L. At Visit 4, at least 20 patients will perform the PK assessment, collecting additional blood samples.

Also known as: Shu Yang IVIG

IVIG

Eligibility Criteria

• Age: 6 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Written informed consent/assent.
• Male or female.
• Ages ≤ 60 years old and ≥ 06 years old.
• Diagnosis of Primary Immunodeficiency Disease (PID) with a reduction in antibody production due to:
• a. Common Variable Immunodeficiency (CVID) as per European Immunodeficiency Society (ESID)/Pan American Immunodeficiency Group (PAGID), as defined in section 5.1, OR b. X-linked agammaglobulinemia (XLA) as per ESID/PAGID, as defined in section 5.1.
• Receiving replacement therapy with intravenous immunoglobulin at 21- to 28-day intervals at 300-600 mg/kg/month for a minimum of 2 months before the start of the study;
• Absence of episodes of serious bacterial infections with previous use of an IV immunoglobulin for at least 3 months before screening;
• Negative pregnancy test (in female patients with childbearing potential); readiness to use reliable methods of contraception throughout the study period;
• Patients who participated in a clinical trial with another experimental IVIG may be enrolled if they have a potential benefit according to Res. CNS 251/1997;
• Patients currently on treatment with any subcutaneous or intramuscular immunoglobulin may be enrolled switching to IVIG therapy at the investigator's discretion, considering the potential benefit to the patient.

You may not qualify if:

• Known intolerance or hypersensitivity to immunoglobulins or components of the test article;
• Any contraindications to the use of immunoglobulins;
• Secondary immunodeficiency or conditions potentially causing secondary immunodeficiency such as chronic lymphoid leukemia, lymphoma, multiple myeloma, protein-losing enteropathies or nephropathies, and hypoalbuminemia;
• Clinically relevant changes in the safety exams are defined as:
• Blood count
• o Hb \< 10.5 g/dL
• o Leukocytes \< 3,000 /uL or \>10,000 cells / uL
• o Absolute neutrophil count \< 1,000 cells/mm3;
• Coagulation o TP and aPTT \> 2.5 x ULN
• Biochemistry o glycated hemoglobin \> 6.5%
• total bilirubin and fractions, alkaline phosphatase, ALT, AST, GGT \> 2.5 x ULN
• creatinine above 3mg/dl or creatinine clearance \< 30mL/min
• Urine I.
• Leukocyturia \> 10,000 cells/mL 5. Any cancer either active or resolved within the last 12 months before screening;
• \. Receiving any blood products (except intravenous immunoglobulins) during the last 3 months before screening;

Sponsors & Collaborators

• Azidus Brasil: lead
• Sichuan Yuanda Shuyang Pharmaceutical Co., Ltd.: collaborator

Related Publications (22)

• Bierry G, Boileau J, Barnig C, Gasser B, Korganow AS, Buy X, Jeung MY, Roy C, Gangi A. Thoracic manifestations of primary humoral immunodeficiency: a comprehensive review. Radiographics. 2009 Nov;29(7):1909-20. doi: 10.1148/rg.297095717.

  PMID: 19926753 BACKGROUND

• Blasczyk R, Westhoff U, Grosse-Wilde H. Soluble CD4, CD8, and HLA molecules in commercial immunoglobulin preparations. Lancet. 1993 Mar 27;341(8848):789-90. doi: 10.1016/0140-6736(93)90563-v.

  PMID: 8096001 BACKGROUND

• Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C, de la Morena MT, Espinosa-Rosales FJ, Hammarstrom L, Nonoyama S, Quinti I, Routes JM, Tang ML, Warnatz K. International Consensus Document (ICON): Common Variable Immunodeficiency Disorders. J Allergy Clin Immunol Pract. 2016 Jan-Feb;4(1):38-59. doi: 10.1016/j.jaip.2015.07.025. Epub 2015 Nov 7.

  PMID: 26563668 BACKGROUND

• BRUTON OC. Agammaglobulinemia. Pediatrics. 1952 Jun;9(6):722-8. No abstract available.

  PMID: 14929630 BACKGROUND

• Busse PJ, Razvi S, Cunningham-Rundles C. Efficacy of intravenous immunoglobulin in the prevention of pneumonia in patients with common variable immunodeficiency. J Allergy Clin Immunol. 2002 Jun;109(6):1001-4. doi: 10.1067/mai.2002.124999.

  PMID: 12063531 BACKGROUND

• Cordero E, Goycochea-Valdivia W, Mendez-Echevarria A, Allende LM, Alsina L, Bravo Garcia-Morato M, Gil-Herrera J, Gudiol C, Len-Abad O, Lopez-Medrano F, Moreno-Perez D, Munoz P, Olbrich P, Sanchez-Ramon S, Soler-Palacin P, Aguilera Cros C, Arostegui JI, Badell Serra I, Carbone J, Fortun J, Gonzalez-Granado LI, Lopez-Granados E, Lucena JM, Parody R, Ramakers J, Regueiro JR, Riviere JG, Roca-Oporto C, Rodriguez Pena R, Santos-Perez JL, Rodriguez-Gallego C, Neth O. Executive Summary of the Consensus Document on the Diagnosis and Management of Patients with Primary Immunodeficiencies. J Allergy Clin Immunol Pract. 2020 Nov-Dec;8(10):3342-3347. doi: 10.1016/j.jaip.2020.05.008.

  PMID: 33161963 BACKGROUND

• Hagan JB, Fasano MB, Spector S, Wasserman RL, Melamed I, Rojavin MA, Zenker O, Orange JS. Efficacy and safety of a new 20% immunoglobulin preparation for subcutaneous administration, IgPro20, in patients with primary immunodeficiency. J Clin Immunol. 2010 Sep;30(5):734-45. doi: 10.1007/s10875-010-9423-4. Epub 2010 May 8.

  PMID: 20454851 BACKGROUND

• Hartung HP, Mouthon L, Ahmed R, Jordan S, Laupland KB, Jolles S. Clinical applications of intravenous immunoglobulins (IVIg)--beyond immunodeficiencies and neurology. Clin Exp Immunol. 2009 Dec;158 Suppl 1(Suppl 1):23-33. doi: 10.1111/j.1365-2249.2009.04024.x.

  PMID: 19883421 BACKGROUND

• Herriot R, Sewell WA. Antibody deficiency. J Clin Pathol. 2008 Sep;61(9):994-1000. doi: 10.1136/jcp.2007.051177.

  PMID: 18755724 BACKGROUND

• Hoffmann F, Grimbacher B, Thiel J, Peter HH, Belohradsky BH; Vivaglobin Study Group. Home-based subcutaneous immunoglobulin G replacement therapy under real-life conditions in children and adults with antibody deficiency. Eur J Med Res. 2010 Jun 28;15(6):238-45. doi: 10.1186/2047-783x-15-6-238.

  PMID: 20696632 BACKGROUND

• IDF Guide for Nurses - Immunoglobulin Therapy for Primary Immunodeficiency Diseases. 4th, pp. 59.

  BACKGROUND

• Milito C, Pulvirenti F, Pesce AM, Digiulio MA, Pandolfi F, Visentini M, Quinti I. Adequate patient's outcome achieved with short immunoglobulin replacement intervals in severe antibody deficiencies. J Clin Immunol. 2014 Oct;34(7):813-9. doi: 10.1007/s10875-014-0081-9. Epub 2014 Jul 22.

  PMID: 25047154 BACKGROUND

• Mouthon L, Kaveri SV, Spalter SH, Lacroix-Desmazes S, Lefranc C, Desai R, Kazatchkine MD. Mechanisms of action of intravenous immune globulin in immune-mediated diseases. Clin Exp Immunol. 1996 May;104 Suppl 1:3-9.

  PMID: 8625540 BACKGROUND

• Orange JS, Hossny EM, Weiler CR, Ballow M, Berger M, Bonilla FA, Buckley R, Chinen J, El-Gamal Y, Mazer BD, Nelson RP Jr, Patel DD, Secord E, Sorensen RU, Wasserman RL, Cunningham-Rundles C; Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology. Use of intravenous immunoglobulin in human disease: a review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol. 2006 Apr;117(4 Suppl):S525-53. doi: 10.1016/j.jaci.2006.01.015.

  PMID: 16580469 BACKGROUND

• Pourpak Z, Aghamohammadi A, Sedighipour L, Farhoudi A, Movahedi M, Gharagozlou M, Chavoshzadeh Z, Jadid L, Rezaei N, Moin M. Effect of regular intravenous immunoglobulin therapy on prevention of pneumonia in patients with common variable immunodeficiency. J Microbiol Immunol Infect. 2006 Apr;39(2):114-20.

  PMID: 16604243 BACKGROUND

• Primary immunodeficiency diseases. Report of an IUIS Scientific Committee. International Union of Immunological Societies. Clin Exp Immunol. 1999 Oct;118 Suppl 1(Suppl 1):1-28. doi: 10.1046/j.1365-2249.1999.00109.x. No abstract available.

  PMID: 10540200 BACKGROUND

• Quinti I, Soresina A, Guerra A, Rondelli R, Spadaro G, Agostini C, Milito C, Trombetta AC, Visentini M, Martini H, Plebani A, Fiorilli M; IPINet Investigators. Effectiveness of immunoglobulin replacement therapy on clinical outcome in patients with primary antibody deficiencies: results from a multicenter prospective cohort study. J Clin Immunol. 2011 Jun;31(3):315-22. doi: 10.1007/s10875-011-9511-0. Epub 2011 Mar 2.

  PMID: 21365217 BACKGROUND

• Radosevich M, Burnouf T. Intravenous immunoglobulin G: trends in production methods, quality control and quality assurance. Vox Sang. 2010 Jan;98(1):12-28. doi: 10.1111/j.1423-0410.2009.01226.x. Epub 2009 Jul 29.

  PMID: 19660029 BACKGROUND

• Salehzadeh M, Aghamohammadi A, Rezaei N. Evaluation of immunoglobulin levels and infection rate in patients with common variable immunodeficiency after immunoglobulin replacement therapy. J Microbiol Immunol Infect. 2010 Feb;43(1):11-7. doi: 10.1016/S1684-1182(10)60002-3. Epub 2010 Mar 29.

  PMID: 20434118 BACKGROUND

• Suri D, Rawat A, Singh S. X-linked Agammaglobulinemia. Indian J Pediatr. 2016 Apr;83(4):331-7. doi: 10.1007/s12098-015-2024-8. Epub 2016 Feb 24.

  PMID: 26909497 BACKGROUND

• WHO. WHO RECOMMENDATIONS FOR THE PRODUCTION, CONTROL AND REGULATION OF HUMAN PLASMA FOR FRACTIONATION. pp. 69.

  BACKGROUND

• Yazdani R, Habibi S, Sharifi L, Azizi G, Abolhassani H, Olbrich P, Aghamohammadi A. Common Variable Immunodeficiency: Epidemiology, Pathogenesis, Clinical Manifestations, Diagnosis, Classification, and Management. J Investig Allergol Clin Immunol. 2020;30(1):14-34. doi: 10.18176/jiaci.0388. Epub 2019 Feb 11.

  PMID: 30741636 BACKGROUND

MeSH Terms

Conditions

Primary Immunodeficiency Diseases

Interventions

Immunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Luciana Ferrara

  Azidus Brasil

  STUDY DIRECTOR

Central Study Contacts

Luciana Ferrara

CONTACT

+55 19 981428814; luciana.ferrara@azidusbrasil.com.br

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Masking Details: The trial will be open-label and single-arm. Therefore, there will be no randomization or blinding.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients with primary immunodeficiency will switch to Shu Yang IVIG and optimize the posology in a run-in period of 2 to 6 administrations. In the one-year test period, the patients will receive the test IVIG at 21- or 28-day intervals and be followed. IgG trough levels will be collected at all visits. At Visit 4, at least 20 patients will perform the PK assessment, collecting additional blood samples.

Study Record Dates

• First Submitted: September 19, 2023
• First Posted: October 18, 2023
• Study Start: April 1, 2024
• Primary Completion: January 8, 2025
• Study Completion: June 8, 2025
• Last Updated: March 12, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share