Study to Investigate Efficacy, Safety and Pharmacokinetics of BT595 in Subjects With PID

An Open-label, Prospective, Multicenter Study Investigating Clinical Efficacy, Safety, and Pharmacokinetic Properties of the Human Normal Immunoglobulin for Intravenous Administration BT595 as Replacement Therapy in Patients With Primary Immunodeficiency Disease (PID)

This Phase III clinical study is to test efficacy, safety and pharmacokinetics of BT595 in treating patients with Primary Immunodeficiency (PID)

Study Overview

• Status: Completed
• Conditions: Primary Immunodeficiency Disease
• Intervention / Treatment: Biological: IgG Next Generation (BT595)

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Frankfurt am Main, Germany, 60528
    • Investigational site # 4902
  • Freiburg, Germany, 79106
    • Investigational site # 4904
  • Leipzig, Germany, 04129
    • Investigational site #4905
• Hungary
  • Budapest, Hungary, 1097
    • Investigational site # 3602
  • Miskolc, Hungary
    • Investigational Site # 3605
  • Nyíregyháza, Hungary, 4400
    • Investigational SIte #3603
• Russian Federation
  • Moscow, Russian Federation, 117198
    • Investigational site # 0702
  • Yekaterinburg, Russian Federation, 620102
    • Investigational site # 0704
• Spain
  • Barcelona, Spain, 08035
    • Investigational site # 3403
  • Madrid, Spain, 28007
    • Investigational Site # 3405
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Investigational site # 0104
  • California
    • Los Angeles, California, United States, 90027
      • Investigational site # 0116
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Investigational site # 0103
    • Thornton, Colorado, United States, 80233
      • Investigational site # 0114
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Investigational site # 0111
  • Indiana
    • South Bend, Indiana, United States, 46617
      • Investigational site # 0106
  • Ohio
    • Toledo, Ohio, United States, 43617
      • Investigational site # 0105
  • Tennessee
    • Memphis, Tennessee, United States, 38103-2800
      • Investigational site #0115
  • Texas
    • Dallas, Texas, United States, 75231
      • Investigational Site # 0102

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Criteria for inclusion:

1. Written informed consent/assent obtained from subjects/subjects' parent(s) or legally acceptable representative indicating that they understood the purpose of, and procedures required for the study and are willing to participate in it.
2. Male or female, aged 2 through 75 years, inclusive.

3. Diagnosis of PID with impaired antibody production, ie:

   - Diagnosis of common variable immunodeficiency (CVID) as defined by the European Society for Immunodeficiencies (ESID)/Pan American Group for Immunodeficiency (PAGID) diagnostic criteria.

   Or

   - X-linked agammaglobulinaemia (XLA) as defined by ESID/PAGID diagnostic criteria.

4. Established replacement therapy with any immunoglobulin for intravenous administration (IVIg) reference preparation during the previous 6 months, including documentation of IgG trough levels.
5. Established replacement therapy with a single IVIg reference preparation for ≥3 months prior to treatment start with BT595 at a 3 week (Q3W) or 4 week (Q4W) schedule with a constant IVIg dose that did not change by ±20% of the mean dose, regular dosage intervals, and at least 1 IgG trough level of ≥5 g/L during the previous 3 months.

Criteria for exclusion:

1. Pregnancy or unreliable contraceptive measures or lactation period (females only).
2. Known intolerance to immunoglobulins or comparable substances (eg, vaccination reaction).
3. Known intolerance to proteins of human origin or known allergic reactions to components of the study product.
4. Participation in another clinical study within 30 days before entering the study or during the study and/or previous participation in this study.
5. Employee or direct relative of an employee of the contract research organization, the study site, or Biotest.
6. Acquired medical conditions known to cause secondary immune deficiency, such as chronic lymphatic leukemia, lymphoma, multiple myeloma, as well as protein losing enteropathies and hypoalbuminemia.
7. Other medical condition, laboratory finding, or physical examination finding that precludes participation.
8. Recent febrile illness that precludes or delays participation.
9. Active infection and receiving antibiotic therapy for the treatment of this infection at the time of screening. Note: if the subject was deemed to be a screen failure due to a nonserious active infection requiring antibiotic therapy, the subject may have been rescreened after the initial screening.
10. Therapy with systemic steroids or other immunosuppressant drugs at the time of enrollment (current daily use of corticosteroids, ie, >10 mg prednisone equivalent/day for >30 days. Intermittent corticosteroid use during the study was allowable, if medically necessary).
11. History of thrombotic events (including myocardial infarction, cerebral vascular accident [including stroke], pulmonary embolism, and deep vein thrombosis) within the 6 months before treatment start with BT595 or the presence of significant risk factors for thrombotic events.
12. Therapy with live-attenuated virus vaccines within 3 months before start of the study.
13. Selective, absolute immunoglobulin A (IgA) deficiency or known antibodies to IgA.
14. Positive diagnosis of hepatitis B or hepatitis C.
15. Positive human immunodeficiency virus (HIV) test.
16. History of drug or alcohol abuse within the 12 months before treatment start with BT595.
17. Inability or lacking motivation to participate in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BT595; Subjects received BT595 (100 mg/mL human normal immunoglobulin) at doses between 0.2 and 0.8 g per kg body weight (bw) (2 to 8 mL/kg bw), either at a Q3W or Q4W schedule, The initial doses and dosage interval had to be consistent with the subject's prestudy IVIg treatment.	Biological: IgG Next Generation (BT595); Other Names: Immune Globulin Intravenous (Human), 10% Liquid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Acute Serious Bacterial Infections	The primary efficacy endpoint was the rate of acute serious bacterial infections, ie, the mean number of acute serious bacterial infections [SBIs as defined by EMA and FDA] per subject-year.	approx. 12 month treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IgG Trough Levels (Total IgG) Before Each Infusion	Total IgG levels [g/L] before each infusion, mean (SD)	approx. 12 month treatment period
Rate of Any Infections	The annual rate of infections was calculated as the number of all infections (serious plus nonserious) per subject-year	approx. 12 month treatment period
Rate of Nonserious Infections	The annual rate of nonserious infections was calculated as the number of nonserious infections per subject-year	approx. 12 month treatment period
Time to Resolution of Infections	Time to resolution of infections (days) was calculated as infection stop date - infection start date +1.	approx. 12 month treatment period
Antibiotic Treatment Information	Median (min-max) number of days on antibiotics treatment per subject	approx. 12 month treatment period
Rate of Time Lost From School/Work Due to Infections	Annual rates of the number of days subjects are not able to attend school/work due to infections and their treatment will be calculated per subject-year.	approx. 12 month treatment period
Hospitalization / Hospitalization Due to Infection	Annual rates of the number of days of hospitalization (any hospitalization/ hospitalization due to infection) will be calculated per subject-year.	approx. 12 month treatment period
Fever Episodes	The number of days with episodes of fever will be calculated as the number of fever episodes per subject-year. Fever is defined as a body temperature ≥38°C (≥100.4°F).	approx. 12 month treatment period

Collaborators and Investigators

• Sponsor: Biotest
• Collaborators: Syneos Health
• Investigators: Principal Investigator: Gergely Krivan, MD, Egyesitett Szent Istvan es Szent Laszlo Korhaz, Budapest, Hungary

Publications and helpful links

General Publications

• Krivan G, Borte M, Harris JB, Lumry WR, Aigner S, Lentze S, Staiger C. Efficacy, safety and pharmacokinetics of a new 10% normal human immunoglobulin for intravenous infusion, BT595, in children and adults with primary immunodeficiency disease. Vox Sang. 2022 Oct;117(10):1153-1162. doi: 10.1111/vox.13337. Epub 2022 Aug 9.
• Krivan G, Borte M, Soler-Palacin P, Church JA, Csurke I, Harris JB, Lieberman JA, Melamed IR, Moy JN, Simon R, Aigner S, Lentze S, Staiger C. BT595, a 10% Human Normal Immunoglobulin, for Replacement Therapy of Primary Immunodeficiency Disease: Results of a Subcohort Analysis in Children. J Clin Immunol. 2023 Apr;43(3):557-567. doi: 10.1007/s10875-022-01397-0. Epub 2022 Nov 16.

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2016
• Primary Completion (Actual): April 1, 2020
• Study Completion (Actual): April 1, 2020

Study Registration Dates

• First Submitted: June 15, 2016
• First Submitted That Met QC Criteria: June 20, 2016
• First Posted (Estimated): June 23, 2016

Study Record Updates

• Last Update Posted (Actual): July 20, 2023
• Last Update Submitted That Met QC Criteria: July 12, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Genetic Diseases, Inborn; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases; Physiological Effects of Drugs; Immunologic Factors; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: 991; 2015-003652-52 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO