Clinical trial NCT02810444: Study to Investigate Efficacy, Safety and Pharmacokinetics of BT595 in Subjects With PID
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Immunodeficiency Disease
Lead sponsor: Biotest
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
First posted: 2016-06-23
Enrollment: 81
Sex: ALL
Minimum age (years): 2
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Rate of Acute Serious Bacterial Infections
timeFrame: approx. 12 month treatment period
Secondary outcomes:
measure: IgG Trough Levels (Total IgG) Before Each Infusion
timeFrame: approx. 12 month treatment period
measure: Rate of Any Infections
timeFrame: approx. 12 month treatment period
measure: Rate of Nonserious Infections
timeFrame: approx. 12 month treatment period
measure: Time to Resolution of Infections
timeFrame: approx. 12 month treatment period
measure: Antibiotic Treatment Information
timeFrame: approx. 12 month treatment period
measure: Rate of Time Lost From School/Work Due to Infections
timeFrame: approx. 12 month treatment period
measure: Hospitalization / Hospitalization Due to Infection
timeFrame: approx. 12 month treatment period
measure: Fever Episodes
timeFrame: approx. 12 month treatment period
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Investigational site # 0104
state: Alabama
city: Los Angeles
country: United States
facility: Investigational site # 0116
state: California
city: Centennial
country: United States
facility: Investigational site # 0103
state: Colorado
city: Thornton
country: United States
facility: Investigational site # 0114
state: Colorado
city: Chicago
country: United States
facility: Investigational site # 0111
state: Illinois
city: South Bend
country: United States
facility: Investigational site # 0106
state: Indiana
city: Toledo
country: United States
facility: Investigational site # 0105
state: Ohio
city: Memphis
country: United States
facility: Investigational site #0115
state: Tennessee
city: Dallas
country: United States
facility: Investigational Site # 0102
state: Texas
city: Frankfurt am Main
country: Germany
facility: Investigational site # 4902
city: Freiburg
country: Germany
facility: Investigational site # 4904
city: Leipzig
country: Germany
facility: Investigational site #4905
city: Budapest
country: Hungary
facility: Investigational site # 3602
city: Miskolc
country: Hungary
facility: Investigational Site # 3605
city: Nyíregyháza
country: Hungary
facility: Investigational site #3603
city: Moscow
country: Russian Federation
facility: Investigational site # 0702
city: Yekaterinburg
country: Russian Federation
facility: Investigational site # 0704
city: Barcelona
country: Spain
facility: Investigational site # 3403
city: Madrid
country: Spain
facility: Investigational site # 3405
Study officials:
affiliation: Egyesitett Szent Istvan es Szent Laszlo Korhaz, Budapest, Hungary
name: Gergely Krivan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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 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.