V-IMMUNE: A Novel Immunoglobulin Therapy for Immunodeficiency

NCT06954441 | Recruiting Phase 3 DMC

• 1 other identifier: VIP study
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase III, non-randomized clinical trial (VIP Study) designed to assess the safety and efficacy of V-IMMUNE®, a 5% human normal immunoglobulin preparation, in approximately 50 patients with primary immunodeficiency (PID). Participants, all aged ≥2 years and already receiving IVIG therapy, will be switched to V-IMMUNE® at a dose of 600 mg/kg every three weeks via intravenous infusion. The study will use historical data as a control and extend over 12 months, with scheduled visits at each infusion (an estimated 17 infusions per participant). Objectives and Outcomes Primary Efficacy Endpoint: Rate of serious bacterial infections over 12 months. Primary Safety Endpoint: Proportion of infusions with one or more temporally associated adverse events (AEs). Secondary Endpoints: Additional safety outcomes (e.g., average number of AEs within 72 hours per infusion), efficacy measures (non-serious bacterial infections, time to resolution, antibiotic use, hospitalizations), and quality of life (SF-36) at 6 and 12 months. A pharmacokinetic (PK) sub-study will be conducted in 20 participants aged ≥16 years to evaluate total IgG levels, half-life, AUC, Cmax, and other PK parameters. Study Design and Intervention V-IMMUNE® is given at an initial infusion rate of 0.01 mL/kg/min for 30 minutes, increasing stepwise up to 0.06 mL/kg/min if well tolerated. Pre-medication, including rapid IV saline, diphenhydramine, and hydrocortisone, will be administered for the first three months to reduce the risk of infusion-related AEs. Patients at elevated thromboembolic risk will receive the lowest feasible infusion rate. Sample Size and Analysis Fifty patients total will be enrolled to ensure adequate power to demonstrate a severe infection rate below one event per person-year (with a one-sided 1% significance level). Safety endpoints will be met if the upper bound of the 95% confidence interval for the proportion of temporally associated infusion-related AEs remains below 40%, assuming a true rate under 20%. An interim analysis is planned at six months or upon reaching 50% enrollment. 20 patients at total including adults and \<16 years old, 6 children from 2 to 12 years old and 6 children from 12 to 16 years old.

Conditions

Immunodeficiencies; Primary Immunodeficiencies (PID); Agammaglobulinemia

Keywords

immunodeficiency; intravenous immunoglobulin; pharmacokinetics; safety; efficacy; serious bacterial infection; temporally related adverse event

Outcome Measures

Primary Outcomes (2)

• Efficacy primary outcome

  The primary efficacy endpoint is the rate of serious bacterial infections per person-year. These serious bacterial infection are: bacteremia/sepsis, bacterial meningitis, osteomielitis/septic arthritis, bacterial pneumonia, visceral abscess Definition of each serious bacterial infection are stated accordinly in the protocol.

  12 months

• Safety outcome

  Proportion of infusions with one or more temporally associated adverse events (AEs)

  72 hours

Secondary Outcomes (21)

• Severe and non-severe bacterial infections

  12 months

• Number of patients with 0, 1, 2, etc., severe infections

  12 months

• Number of adverse events by body systems

  12 months

• Time to first infection

  12 months

• Nadir of pre-infusion total IgG level

  3 weeks

Other Outcomes (6)

• Cmax

  12 months

• ASC0-t

  12 months

• Tmax

  12 months

Study Arms (1)

Intervention arm

EXPERIMENTAL

Human normal immunoglobulin I.P. 5% (5 g/100 mL) V-IMMUNE® will be administered at a dose of 600 mg/kg every 3 weeks (±3 days) via intravenous (IV) infusion according to the rate below, over a duration of 3 to 6 hours (4): 0.01 mL/kg/min from 0 to 30 minutes, followed by the following infusion rates: 0.02 mL/kg/min from 31 to 45 minutes 0.04 mL/kg/min from 46 to 60 minutes 0.06 mL/kg/min from 61 minutes until the end of the infusion The dose increases gradually unless adverse events (AEs) occur. The infusion rate is only increased if the patient tolerates it well, with no AEs. If an AE occurs, the infusion must be interrupted for 20 to 30 minutes. Pre-medication: 30 to 60 min before Ig Rapid administration of 500 mL of 0.9% NaCl IV Diphenhydramine\* 50 mg IV (adult). Pediatrics: 1.25 mg/kg IV Hydrocortisone\*\* 200 mg IV (adult). Pediatrics: 3 mg/kg IV After infusion: 0.9% NaCl at 1 mL/kg/hour for one hour After three months, diphenhydramine and hydrocortisone may no loger be needed

Biological: Intravenous immunoglobulin (IVIG)

Interventions

Intravenous immunoglobulin (IVIG) BIOLOGICAL

The investigational product is V-IMMUNE®, a 5% human normal immunoglobulin I.P. (5 g/100 mL) manufactured from qualified human plasma for intravenous use. Each vial contains human immunoglobulin at 50 g/L, maltose at 100 g/L, and water for injection. The 5% Human Immunoglobulin Solution for Intravenous Administration (I.P.) is a sterile and pyrogen-free preparation of human normal immunoglobulin in a single-dose form for intravenous administration. Each 10 mL, 50 mL, or 100 mL vial contains 0.5 g, 2.5 g, or 5 g of human normal immunoglobulin, respectively, and is produced from qualified human plasma using membrane filtration and a combination of chromatographic steps and viral inactivation procedures. The IgA content does not exceed 2 mg/mL. This manufacturing process uses plasma collected from donors who undergo screening according to guidelines set by regulatory authorities. In case of thromboembolic risk: use the lowest feasible dose

Also known as: V-IMMUNE

Intervention arm

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 2 years or older;
• Primary immunoglobulin G deficiency, already receiving another intravenous immunoglobulin (IVIG). Primary IgG deficiency may be secondary (non-exhaustive list) to one of the following diagnoses:
• Agammaglobulinemia due to absence of B cells
• Hypogammaglobulinemia with reduced antibody function - variable common immunodeficiency complex
• Quantitative and functional deficiencies of immunoglobulin G
• Normal immunoglobulin with reduced capacity for antibody production after immunization (e.g., Wiskott-Aldrich syndrome, IgG subclass deficiency, antipolysaccharide antibody deficiency against Haemophilus or pneumococcus)
• Severe combined immunodeficiencies: DiGeorge syndrome presenting with immunoglobulin G deficiency
• Isotype-switching defects: hyperimmunoglobulinemia M syndromes
• Two trough IgG measurements ≥500 mg/dL within the past 90 days.
• Participants with through IgG measurements ≥700 mg/dL within the last 30 days before the first visit

You may not qualify if:

• Acute infection under treatment within 2 weeks prior to screening
• Pregnancy
• History of hypersensitivity reaction to blood or blood products
• Previous anaphylactic reaction to IgG
• Intolerance to any component of V-Immune
• IgA deficiency, history of reactions to products containing IgA, or history of anti-IgA antibodies
• Selective Deficiency of IgA, IgM, IgD, or IgE
• Participation in any other study involving an investigational product
• Exposure to blood or any blood-derived products in the last 3 months
• Known HIV, HCV, or HBV infection
• ALT \>3× the upper limit of normal or 3x baseline value
• Serum creatinine \>2× the upper limit of normal or 2x baselline value
• BUN \>2.5× the upper limit of normal or 2.5x baseline value
• History of NYHA class III/IV heart failure
• Uncontrolled hypertension with systolic BP \>160 mmHg or diastolic BP \>100 mmHg

Sponsors & Collaborators

• Hospital do Coracao: collaborator
• On Pharma Importadora, Exportadora e Distribuidora de Medicamentos LTDA.: lead

Study Sites (1)

IMIP Centro de Pesquisa

Recife, Pernanbuco, 50070-902, Brazil

RECRUITING

Related Publications (3)

• FDA. 2008. Guidance for Industry: Safety, Efficacy, and Pharmacokinetic Studies to Support Marketing of Immune Globulin Intravenous (Human) as Replacement Therapy for Primary Humoral Immunodeficiency

  BACKGROUND

• Goudouris ES, Silva AMDR, Ouricuri AL, Grumach AS, Condino-Neto A, Costa-Carvalho BT, Prando CCM, Kokron CM, Vasconcelos DM, Tavares FS, Segundo GRS, Barreto ICDP, Dorna MB, Barros MAMT, Forte WCN. Comment to: II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies. einstein (Sao Paulo). 2017;15(1):1-16. Einstein (Sao Paulo). 2017 Oct-Dec;15(4):522. doi: 10.1590/S1679-45082017CE4250. No abstract available.

  PMID: 29364371 BACKGROUND

• Buckley RH, Schiff RI. The use of intravenous immune globulin in immunodeficiency diseases. N Engl J Med. 1991 Jul 11;325(2):110-7. doi: 10.1056/NEJM199107113250207. No abstract available.

  PMID: 2052044 BACKGROUND

Related Links

• Sponsor´s website

MeSH Terms

Conditions

Immunologic Deficiency Syndromes; Agammaglobulinemia

Interventions

Immunoglobulins, Intravenous; V-Set Domain-Containing T-Cell Activation Inhibitor 1

Condition Hierarchy (Ancestors)

Immune System Diseases; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; B7 Antigens; Intercellular Signaling Peptides and Proteins; Membrane Proteins; Antigens, Surface; Antigens; Biological Factors

Study Officials

• Israel Silva Maia, PhD

  Hospital do Coracao

  STUDY CHAIR

• Dewton Moraes Vasconcelos, PhD

  Hospital do Coracao

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Israel Silva Maia, PhD

CONTACT

+55 48 9 84131510; ismaia@hcor.com.br

Dewton Moraes Vasconcelos, PhD

CONTACT

dewton.vasconcelos@hc.fm.usp.br

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Masking Details: no masking
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All participants will get the same intervention: IV immunoglobulin each 3 weeks. Participants meeting the inclusion criteria will receive V-IMMUNE® at a dose of 600 mg/kg, with infusion rates progressively increased to a maximum of 0.06 mL/kg/min, provided no adverse events occur. Pre-medication with intravenous normal saline, hydrocortisone and diphenhydramine is administered to mitigate infusion-related risks.

Study Record Dates

• First Submitted: April 15, 2025
• First Posted: May 1, 2025
• Study Start: August 15, 2025
• Primary Completion (Estimated): September 27, 2026
• Study Completion (Estimated): February 27, 2027
• Last Updated: January 20, 2026

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)