Efficacy and Safety and Pharmacokinetics of Boya IVIG (Boya)

November 21, 2023 updated by: Azidus Brasil

Efficacy, Safety and Pharmacokinetics of Boya Intravenous Immunoglobulin (IVIG) in Participants With Primary Immunodeficiency

To evaluate the safety, efficacy and pharmacokinetic properties of Boya's IVIG preparation in participants with PID aged less than 60 years and more than 6 years.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a phase 3, open-label, prospective, single-group, multicenter study to evaluate the efficacy of IVIG in keeping the average number of serious bacterial infections to less than one per year. The safety and pharmacokinetics (PK) of the investigational product will also be assessed. Fifty male or female participants aged up to 60 years will be selected, with at least 20 participants aged between 06 and 17 years. During the study, at least 20 adult participants will be invited to make up the subgroups evaluating the pharmacokinetic parameters.

The main benefit of IVIG is to help the immune system respond to a wide range of infections, which are often correlated with high morbidity and mortality rates in individuals with PID, particularly in cases of CVID and XLA. In addition, a reduction in the use of medication and hospitalizations is expected, promoting an improvement in the quality of life of these patients.

IVIG therapy is generally safe, although unwanted effects are reported in a proportion ranging from 1% to 81% of patients or infusions, with an average incidence of 30% to 40% among patients and 5% to 15% among infusions. These effects can manifest themselves in varying degrees of intensity, ranging from mild to severe. They can occur immediately, during or shortly after the infusion, as well as late, appearing hours or even days after the procedure. Most adverse events are mild and immediate, occurring in the first few infusions, related to the infusion rate and quickly reversible.

Headache, fever, general malaise, flu-like symptoms, nausea, chills, fatigue, myalgia, low back pain, tachycardia, changes in blood pressure and erythroderma are the most common events. Serious reactions occur in less than 1% of applications and usually with the use of higher doses, indicated in autoimmune and inflammatory diseases.

Special care is needed in patients with comorbidities such as heart disease, nephropathy, liver disease, coagulation disorders (thrombophilia) and diabetes mellitus. In these patients, certain characteristics of IVIG should be assessed, such as the presence of sugars, osmolality, sodium, among others.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Signature of written informed consent.
  2. Men or women.
  3. Age ≤ 60 years.

  4. Diagnosis of PID disease (PID) with a reduction in antibody production due to:

    1. Common variable immunodeficiency (CVID) as defined ESID/PAGID, OR
    2. X-linked agammaglobulinemia (XLA) as defined by ESID/PAGID.
  5. Receiving intravenous immunoglobulin replacement therapy at 21- or 28-day intervals at 300 to 600 mg/kg/month for a minimum of 2 months prior to study entry.
  6. Absence of episodes of serious bacterial infections with prior use of IV immunoglobulin for at least 3 months prior to screening.
  7. Negative pregnancy test (in female participants of childbearing potential); readiness to use reliable contraceptive methods throughout the study period.
  8. Patients who have participated in a clinical study with another investigational IVIG may be included if they have a potential benefit in accordance with CNS Res. 251/1997.
  9. Participants undergoing treatment with any subcutaneous or intramuscular immunoglobulin may be included by switching to IVIG therapy at the discretion of the investigator, considering the possible benefit to the participant.

Exclusion Criteria:

  1. Known intolerance or hypersensitivity to immunoglobulins or components of the test article;
  2. Any contraindications to the use of immunoglobulins;
  3. Secondary immunodeficiency or conditions potentially causing secondary immunodeficiency such as chronic lymphoid leukemia, lymphoma, multiple myeloma, protein-losing enteropathies or nephropathies, and hypoalbuminemia;

  4. Clinically relevant changes in the safety exams are defined as:

    • Blood count

      • Hb < 10.5 g/dL
      • Leukocytes < 3,000 / mm3 or >10,000 cells / mm3
      • Absolute neutrophil count < 1,000 cells/mm3;

    • Coagulation

      • TP and aPTT > 2.5 x ULN

    • Biochemistry

      • 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;
  6. Receiving any blood products (except intravenous immunoglobulins) during the last 3 months before screening;
  7. Any febrile illness within 14 days before enrollment; Note: The patient may be rescreened after recovery.
  8. History of thrombotic events (including myocardial infarction, stroke, pulmonary embolism, and deep vein thrombosis) within 6 months before enrollment;
  9. Previous use of live attenuated virus vaccines;
  10. Selective deficiency of immunoglobulin A (IgA) or known antibodies to IgA;
  11. Known drug or alcohol abuse;
  12. The need to use other investigational drugs, systemic immunosuppressants, and any other immunoglobulins;
  13. Pregnancy or lactation;
  14. Inability to comply with the protocol activities;
  15. PIDs other than CVID or X-linked agammaglobulinemia
  16. Patients infected with HIV, HBV or HCV
  17. Patients with AIDS, cystic fibrosis, or active hepatitis B or C.
  18. Any other condition that, in the Investigator's opinion may increase the risk of participation in this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Boya IVIG
Patients with primary immunodeficiency will switch to Boya 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. The minimum IgG concentration will be measured in all participants at all visits. The other pharmacokinetic parameters will be measured between visits 4 and 5 in 20 adult participants by taking additional blood samples. An independent Safety Data Monitoring Committee (SDMC) will periodically monitor adverse events.
Biological: Boya IVIG

The initial dose and other dose changes will be determined by the investigator on a case-by-case basis aiming to prevent infection and minimum serum IgG levels of 5 g/L. The total number of doses administered will depend on the treatment regimen and run-in period:

  • Between 16 and 20 intravenous injections for participants receiving infusions every 28 days, or;
  • Between 21 and 25 intravenous injections for participants receiving infusions every 21 days
Other Names:
  • IVIG
  • BOYA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Efficacy Objective (average of acute serious bacterial infections)
Time Frame: Between Visit 0 and Final Visit (through study completion, an average of 1 year)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of the rate of non-serious infections within one year
Time Frame: 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).
The incidence of all acute infections except the serious acute bacterial infections within the 1-year follow-up (simple descriptive statistics).
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).
Length of infections
Time Frame: 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)
Assessment of the duration of treatment for infections per year
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)
Missing time from school/work
Time Frame: 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)
Assessment of time lost at school/work due to infections per month
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)
Hospitalization episodes
Time Frame: 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)
Assessment of hospitalization episodes and length
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Secondary Pharmacokinetic (PK) Objectives
Time Frame: 9 months
To assess the total IgG serum concentration before each infusion (IgG trough levels), between Visit 4 and Final Visit (through study completion).
9 months
Secondary Pharmacokinetic (PK) Objectives
Time Frame: 28 days
To assess total serum IgG profile (concentration vs time) at specific times between the 5th and 6th infusion
28 days
IgG half-life
Time Frame: 28 days
Determine IgG half-life from concentration vs time curve
28 days
Area under the IgG curve
Time Frame: 28 days
Determine IgG AUC from concentration vs time curve
28 days
IgG distribution volume
Time Frame: 28 days
Determine IgG Vd from concentration vs time curve
28 days
IgG elimination constant
Time Frame: 28 days
Determine IgG Kel from concentration vs time curve
28 days
Incidence, severity, and causality of adverse events
Time Frame: 1, 24, and 72 hours after each infusion (through study completion, an average of 1 year)
Assessment of infusion-related adverse events
1, 24, and 72 hours after each infusion (through study completion, an average of 1 year)
Secondary Safety Objective
Time Frame: Incidence, severity, and causality of all treatment-emergent adverse events, except those infusion-related (through study completion, an average of 1 year).
Assessment of treatment emergent adverse events (TEAEs)
Incidence, severity, and causality of all treatment-emergent adverse events, except those infusion-related (through study completion, an average of 1 year).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azidus Brasil

Collaborators

Boya Bio Pharmaceutical Group Co Ltd

Investigators

  • Study Director: Luciana Ferrara, Azidus Brasil

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2024

Primary Completion (Estimated)

April 30, 2025

Study Completion (Estimated)

September 30, 2025

Study Registration Dates

First Submitted

November 21, 2023

First Submitted That Met QC Criteria

November 21, 2023

First Posted (Actual)

November 29, 2023

Study Record Updates

Last Update Posted (Actual)

November 29, 2023

Last Update Submitted That Met QC Criteria

November 21, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BoyaIVIG

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

It is believed that after the data analysis and presentation to the National Commission on Research Ethics, all data of the study will become public.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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