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)

• Register: EUCTR
• Last refreshed on: 16 December 2019
• Main ID: EUCTR2015-003652-52-DE
• Date of registration: 18/05/2016
• Prospective Registration: Yes
• Primary sponsor: Biotest AG
• Public 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)
• Scientific 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)
• Date of first enrolment: 29/09/2016
• Target sample size: 70
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003652-52
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Russian Federation, Spain, United Kingdom, United States

Contacts

• Name: Clinical Trial Information
• Affiliation: Biotest AG

• Name: Clinical Trial Information
• Affiliation: Biotest AG

Key inclusion & exclusion criteria

Inclusion criteria:
a) Written informed consent/assent obtained from subjects/subjects’ parent(s) or legally acceptable representative indicating that they understand the purpose of and procedures required for the study and are willing to participate in it.
b) Male or female, aged 2 through 75 years.
c) Diagnosis of PID with impaired antibody production, i.e.:
- 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 agammaglobulinemia (XLA) as defined by ESID/PAGID diagnostic criteria.
d) Established replacement therapy with any intravenous immunoglobulin (IVIg) reference preparation during the previous 6 months, including documentation of immunoglobulin G (IgG) trough levels.
e) Established replacement therapy with a single IVIg reference preparation for at least 3 months prior to treatment start with BT595 at a 3 or 4 week 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.

Are the trial subjects under 18? yes
Number of subjects for this age range: 20
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 44
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
a) Pregnancy or unreliable contraceptive measures or lactation period (females only).
b) Known intolerance to immunoglobulins or comparable substances (e.g., vaccination reaction).
c) Known intolerance to proteins of human origin or known allergic reactions to components of the study product.
d) Participation in another clinical study within 30 days before entering the study or during the study and/or previous participation in this study.
e) Employee or direct relative of an employee of the Contract Research Organization, the study site, or Biotest.
f) 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.
g) Other medical condition, laboratory finding, or physical examination finding that precludes participation.
h) Recent febrile illness that precludes or delays participation.
i) Active infection and receiving antibiotic therapy for the treatment of this infection at the time of screening. Note: if the subject is deemed to be a screen failure due to a nonserious active infection requiring antibiotic therapy, the subject may be rescreened after the initial screening.
j) Therapy with systemic steroids or other immunosuppressant drugs at the time of enrollment (current daily use of corticosteroids, i.e., >10 mg prednisone equivalent/day for >30 days. Intermittent corticosteroid use during the study is allowable, if medically necessary).
k) 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.
l) Therapy with live attenuated virus vaccines within 3 months before start of the study.
m) Selective, absolute immunoglobulin A (IgA) deficiency or known antibodies to IgA.
n) Positive diagnosis of hepatitis B or hepatitis C.
o) Positive HIV test.
p) History of drug or alcohol abuse within the 12 months before treatment start with BT595.
q) Inability or lacking motivation to participate in the study.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Replacement therapy in patients with primary immunodeficiency disease (PID)
MedDRA version: 20.0 Level: PT Classification code 10064859 Term: Primary immunodeficiency syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: IgG Next Generation
Product Code: BT595
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: HUMAN NORMAL IMMUNOGLOBULIN (IV)
Current Sponsor code: BT595
Other descriptive name: HUMAN NORMAL IMMUNOGLOBULIN (IV)
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Primary end point(s): Rate of acute serious bacterial infections
(i.e., the mean number of acute serious bacterial infections per subject year).
Acute serious bacterial infections include:
• Bacteremia or sepsis
• Bacterial meningitis
• Osteomyelitis/septic arthritis
• Bacterial pneumonia
• Visceral abscess

Secondary Objective: The secondary objectives of this study, in addition to further efficacy assessments, are to evaluate the safety and pharmacokinetic characteristics of BT595.

Timepoint(s) of evaluation of this end point: after 12 months/per subject

Main Objective: The primary objective of this study is to demonstrate that the rate of acute serious bacterial infections (i.e., the mean number of acute serious bacterial infections per subject year) is less than 1.0 to provide substantial evidence of efficacy.

Secondary Outcome(s)

Secondary end point(s): • IgG trough levels (total IgG) before each infusion
• Rate of any infections (number per year)
• Rate of nonserious infections (number per year)
• Time to resolution of infections
• Antibiotic treatment (number of days antibiotic treatment received per month)
• Rate of time lost from school/work due to infections (number of days per month) and their treatment (number of days treatment per month)
• Hospitalization (number of days per month overall and due to infection)
• Fever episodes (number of days per year)
• Changes in health-related quality of life: Pediatric subjects (2 17 years, inclusive) will complete the Pediatric Quality of Life (Peds QL™) Measurement Model (child self report and/or parent proxy report). Additionally, all adult subjects will complete the EuroQol Five Dimension (EQ 5D 3L™) Health Questionnaire and pediatric subjects (4 17 years, inclusive) will complete the youth version of the EQ 5D™ (EQ 5D Y™) Health Questionnaire (child self report or proxy report).

Timepoint(s) of evaluation of this end point: after 12 months/per subject

Secondary ID(s)

017046

991

NCT02810444

Source(s) of Monetary Support

Biotest AG

Ethics review

Status: Approved
Approval date:
Contact: