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

NCT02810444 | Completed Phase 3 Results DMC

• 2 other identifiers: 9912015-003652-52
• Study Type: interventional
• Target: 81
• Locations: 5 countries
• Sites: 19

Brief Summary

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

Conditions

Primary Immunodeficiency Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• IgG Trough Levels (Total IgG) Before Each Infusion

  approx. 12 month treatment period

• Rate of Any Infections

  approx. 12 month treatment period

• Rate of Nonserious Infections

  approx. 12 month treatment period

• Time to Resolution of Infections

  approx. 12 month treatment period

• Antibiotic Treatment Information

  approx. 12 month treatment period

Study Arms (1)

BT595

EXPERIMENTAL

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)

Interventions

IgG Next Generation (BT595) BIOLOGICAL

Also known as: Immune Globulin Intravenous (Human), 10% Liquid

BT595

Eligibility Criteria

• Age: 2 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Male or female, aged 2 through 75 years, inclusive.
• 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.
• \- X-linked agammaglobulinaemia (XLA) as defined by ESID/PAGID diagnostic criteria.
• Established replacement therapy with any immunoglobulin for intravenous administration (IVIg) reference preparation during the previous 6 months, including documentation of IgG trough levels.
• 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.

You may not qualify if:

• Pregnancy or unreliable contraceptive measures or lactation period (females only).
• Known intolerance to immunoglobulins or comparable substances (eg, vaccination reaction).
• Known intolerance to proteins of human origin or known allergic reactions to components of the study product.
• Participation in another clinical study within 30 days before entering the study or during the study and/or previous participation in this study.
• Employee or direct relative of an employee of the contract research organization, the study site, or Biotest.
• 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.
• Other medical condition, laboratory finding, or physical examination finding that precludes participation.
• Recent febrile illness that precludes or delays participation.
• 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.
• 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).
• 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.
• Therapy with live-attenuated virus vaccines within 3 months before start of the study.
• Selective, absolute immunoglobulin A (IgA) deficiency or known antibodies to IgA.
• Positive diagnosis of hepatitis B or hepatitis C.
• Positive human immunodeficiency virus (HIV) test.

Sponsors & Collaborators

• Biotest: lead
• Syneos Health: collaborator

Study Sites (19)

Investigational site # 0104

Birmingham, Alabama, 35294, United States

Location

Investigational site # 0116

Los Angeles, California, 90027, United States

Location

Investigational site # 0103

Centennial, Colorado, 80112, United States

Location

Investigational site # 0114

Thornton, Colorado, 80233, United States

Location

Investigational site # 0111

Chicago, Illinois, 60612, United States

Location

Investigational site # 0106

South Bend, Indiana, 46617, United States

Location

Investigational site # 0105

Toledo, Ohio, 43617, United States

Location

Investigational site #0115

Memphis, Tennessee, 38103-2800, United States

Location

Investigational Site # 0102

Dallas, Texas, 75231, United States

Location

Investigational site # 4902

Frankfurt am Main, 60528, Germany

Location

Investigational site # 4904

Freiburg im Breisgau, 79106, Germany

Location

Investigational site #4905

Leipzig, 04129, Germany

Location

Investigational site # 3602

Budapest, 1097, Hungary

Location

Investigational Site # 3605

Miskolc, Hungary

Location

Investigational site #3603

Nyíregyháza, 4400, Hungary

Location

Investigational site # 0702

Moscow, 117198, Russia

Location

Investigational site # 0704

Yekaterinburg, 620102, Russia

Location

Investigational site # 3403

Barcelona, 08035, Spain

Location

Investigational site # 3405

Madrid, 28007, Spain

Location

Related 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. 2022 Oct;117(10):1153-1162. doi: 10.1111/vox.13337. Epub 2022 Aug 9.

  PMID: 35944615 RESULT

• 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.

  PMID: 36383294 RESULT

MeSH Terms

Conditions

Primary Immunodeficiency Diseases

Interventions

gamma-Globulins; Fluid Therapy

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Dr. med. Andrea Wartenbrg-Demand
• Organization: Biotest AG

andrea.wartenberg-demand@biotest.com

+49 6103 801

Study Officials

• Gergely Krivan, MD

  Egyesitett Szent Istvan es Szent Laszlo Korhaz, Budapest, Hungary

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2016
• First Posted: June 23, 2016
• Study Start: October 4, 2016
• Primary Completion: April 1, 2020
• Study Completion: April 1, 2020
• Last Updated: July 20, 2023
• Results First Posted: July 12, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (9); RU (2); DE (3); HU (3); ES (2)