Efficacy, Safety, Tolerability, Immunogenicity and Pharmacokinetic Evaluation of HYQVIA in Pediatric PIDD Subjects

NCT03277313 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 161503
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 19

Brief Summary

The purpose of the study is to acquire additional data on efficacy, safety, tolerability, immunogenicity, pharmacokinetic (PK) and other parameters of HYQVIA in pediatric (age ≥ 2 to \<16 years) participants with primary immunodeficiency disease (PIDD).

Conditions

Primary Immunodeficiency Diseases (PID)

Outcome Measures

Primary Outcomes (1)

• Rate Represented as Mean Number of Acute Serious Bacterial Infections (ASBI) Per Participant-year

  The rate of ASBI was defined as the mean number of ASBI per participant-year based on the United States (U.S.) Food and drugs Administration (FDA) guidance for industry to support marketing of human immune globulin intravenous (IGIV) as replacement therapy for primary humoral immunodeficiency and the European Medicines Agency (EMA) guideline on the clinical investigation of human normal immunoglobulin for SC and /or intramuscular administration. ASBI included bacteremia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess, diagnosed according to the Diagnostic Criteria for Acute Serious Bacterial Infections.

  From first dose of study drug up to end of Study Epoch 2 (up to approximately 37.2 months)

Secondary Outcomes (46)

• Rate Represented as Mean Number of All Infections Per Participant-year

  From first dose of study drug up to end of Study Epoch 2 (up to approximately 37.2 months)

• Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses

  Study Epoch 2, Year 1: Months 0, 6, and 12; Year 2: Months 18, 24 and 36

• Epoch 2: Trough Levels of Specific Antibodies to Clinically Relevant Pathogens Categorized as Clostridium Tetani Toxoid and Hepatitis B Virus

  Study Epoch 2, Year 2: Months 6, 24, and 36

• Epoch 2: Trough Levels of Specific Antibodies to Clinically Relevant Pathogen Haemophilus Influenzae B

  Study Epoch 2, Year 2: Months 6, 24, and 36

• Epoch 2: Area Under the Curve Normalized for Week (AUCweek)

  Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion

Study Arms (2)

Epoch 1

EXPERIMENTAL

Pediatric participants with PIDD who were on IV or non-HYQVIA SC treatment with immunoglobulin were enrolled and treated with HYQVIA SC with a dose or interval ramp-up period of up to six weeks. HYQVIA dose was planned to be equivalent to 100% (± 5%) of pre-study treatment. Dose frequency was one treatment interval of one week, then one treatment interval of two weeks for participants who were planned to be treated every three weeks, and one more treatment interval of three weeks for participants who were planned to be treated every four weeks.

Biological: HYQVIA

Epoch 2

EXPERIMENTAL

Epoch 1 was followed by Epoch 2 with HYQVIA treatment infusions given once every 3 or 4 weeks, depending on the participant's previous IV dosing schedule (for IV pretreated participants) and at the discretion of the investigator and participant (for SC-pretreated participants) up to approximately 36 months.

Biological: HYQVIA

Interventions

HYQVIA BIOLOGICAL

Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase (IGI, 10% with rHuPH20)

Also known as: IGI 10% with rHuPH20

Epoch 1; Epoch 2

Eligibility Criteria

• Age: 2 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participant must have a documented diagnosis of a form of primary immunodeficiency (PI) involving a defect in antibody formation and requiring gammaglobulin replacement, as defined according to the International Union of Immunological Societies (IUIS) Scientific Committee 2015 (Picard et al., 2015) prior to enrollment. The diagnosis must be confirmed by the sponsor´s Medical Director prior to first treatment with IP in the study.
• Participant is at least two and below 16 years of age at the time of screening.
• Participant has been receiving a consistent dose of Immunoglobulin G (IgG), administered in compliance with the respective product information for a period of at least three months prior to screening. The average minimum pre-study dose over that interval was equivalent to 300 mg/kg BW / 4 weeks and a maximum dose equivalent to 1000 mg/kg body weight (BW) / 4 weeks.
• Participant has a serum trough level of IgG \> 5 g/L at screening.
• If female of childbearing potential, participant presents with a negative pregnancy test and agrees to employ adequate birth control measures for the duration of the study.
• Participant /legally authorized representative is willing and able to comply with the requirements of the protocol.

You may not qualify if:

• Participant has a known history of or is positive at screening for one or more of the following: hepatitis B surface antigen (HBsAg), polymerase chain reaction (PCR) for hepatitis C virus (HCV), PCR for human immunodeficiency virus (HIV) Type 1/2.
• Abnormal laboratory values at screening meeting any one of the following criteria (abnormal tests may be repeated once to determine if they are persistent):
• Persistent alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \> 2.5 times the upper limit of normal (ULN) for the testing laboratory
• Persistent severe neutropenia (defined as an absolute neutrophil count \[ANC\] ≤ 500/mm\^3)
• Participant has anemia that would preclude phlebotomy for laboratory studies, according to standard practice at the site.
• Participant has an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following intravenous (IV) immunoglobulin, subcutaneous (SC) immunoglobulin, and/or Immune Serum Globulin (ISG) infusions.
• Participant has severe Immunoglobulin A (IgA) deficiency (less than 7.0 mg/dL) with known anti-IgA antibodies and a history of hypersensitivity.
• Participant has a known allergy to hyaluronidase.
• Participant has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening.
• Participant has a bleeding disorder or a platelet count less than 20,000/μL, or who, in the opinion of the investigator, would be at significant risk of increased bleeding or bruising as a result of SC therapy.
• Participant has severe dermatitis that would preclude adequate sites for safe product administration in the opinion of the investigator.
• Participant has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
• Participant is a family member or employee of the investigator.
• If female, participant is pregnant or lactating at the time of enrollment.

Sponsors & Collaborators

• Baxalta now part of Shire: lead
• Baxalta Innovations GmbH, now part of Shire: collaborator

Study Sites (19)

University of Alabama Medical Center

Birmingham, Alabama, 35294, United States

Location

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

Location

University of Miami Pediatric Allergy and Immunology

Miami, Florida, 33136, United States

Location

University of South Florida Physician Group

St. Petersburg, Florida, 33701, United States

Location

Georgia Pollens Clinical Research Centers, Inc.

Albany, Georgia, 31707, United States

Location

Emory Healthcare

Atlanta, Georgia, 30322, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Women & Children's Hospital of Buffalo

Buffalo, New York, 14203, United States

Location

Northwell Health, Inc. PRIME

Great Neck, New York, 11021, United States

Location

Stony Brook Children's Hospital

Stony Brook, New York, 11794, United States

Location

Carolinas Healthcare System

Charlotte, North Carolina, 28203, United States

Location

Allergy Asthma & Immunology Relief of Charlotte

Charlotte, North Carolina, 28277, United States

Location

OK Institute of Allergy & Asthma Clinical Research, LLC

Oklahoma City, Oklahoma, 73131, United States

Location

Vital Prospects Clinical Research Institute, P.C.

Tulsa, Oklahoma, 74136, United States

Location

Allergy Partners of North Texas Research

Dallas, Texas, 75230, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Section on Immunopathogenesis and Clinical Immunology

Fairfax, Virginia, 22030, United States

Location

Marshall University Joan C. Edwards School of Medicine

Charleston, West Virginia, 25701, United States

Location

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Conditions

Primary Immunodeficiency Diseases

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Takeda

ClinicalTransparency@takeda.com

+1 866 842 5335

Study Officials

• Study Director

  Shire

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: September 7, 2017
• First Posted: September 11, 2017
• Study Start: September 25, 2017
• Primary Completion: July 20, 2022
• Study Completion: July 20, 2022
• Last Updated: October 23, 2023
• Results First Posted: October 23, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (19)