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

Primary Immunodeficiency Disease Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02810444
• Other study ID #: 991
• Secondary ID: 2015-003652-52
• Status: Completed
• Phase: Phase 3
• Start date: October 4, 2016
• Est. completion date: April 1, 2020

Study information

• Verified date: July 2023
• Source: Biotest
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: April 1, 2020
• Est. primary completion date: April 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Immunologic Deficiency Syndromes
• Primary Immunodeficiency Disease
• Primary Immunodeficiency Diseases

Intervention

Biological:
• IgG Next Generation (BT595)

Locations

Country	Name	City	State
Germany	Investigational site # 4902	Frankfurt am Main
Germany	Investigational site # 4904	Freiburg
Germany	Investigational site #4905	Leipzig
Hungary	Investigational site # 3602	Budapest
Hungary	Investigational Site # 3605	Miskolc
Hungary	Investigational site #3603	Nyíregyháza
Russian Federation	Investigational site # 0702	Moscow
Russian Federation	Investigational site # 0704	Yekaterinburg
Spain	Investigational site # 3403	Barcelona
Spain	Investigational site # 3405	Madrid
United States	Investigational site # 0104	Birmingham	Alabama
United States	Investigational site # 0103	Centennial	Colorado
United States	Investigational site # 0111	Chicago	Illinois
United States	Investigational Site # 0102	Dallas	Texas
United States	Investigational site # 0116	Los Angeles	California
United States	Investigational site #0115	Memphis	Tennessee
United States	Investigational site # 0106	South Bend	Indiana
United States	Investigational site # 0114	Thornton	Colorado
United States	Investigational site # 0105	Toledo	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Biotest	Syneos Health

Countries where clinical trial is conducted

United States,  Germany,  Hungary,  Russian Federation,  Spain, 

References & Publications (2)

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. — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	IgG Trough Levels (Total IgG) Before Each Infusion	Total IgG levels [g/L] before each infusion, mean (SD)	approx. 12 month treatment period
Secondary	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
Secondary	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
Secondary	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
Secondary	Antibiotic Treatment Information	Median (min-max) number of days on antibiotics treatment per subject	approx. 12 month treatment period
Secondary	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
Secondary	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
Secondary	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