Post-Authorization Safety, Tolerability and Immunogenicity Evaluation of HyQvia in Pediatric PIDD Subjects

NCT03116347 | Completed Phase 4 Results

• 2 other identifiers: 1615042016-003438-26
• Study Type: interventional
• Target: 42
• Locations: 8 countries
• Sites: 20

Brief Summary

The purpose of the study is to acquire additional data on safety, tolerability and immunogenicity of HyQvia in pediatric (age two to \<18 years) patients with Primary Immunodeficiency Diseases (PIDD)

Conditions

Primary Immunodeficiency Diseases (PID)

Outcome Measures

Primary Outcomes (4)

• Safety: Number of Participants With Any Severe Related Treatment-emergent Adverse Events (TEAEs) Per Infusion (Excluding Infections)

  An Adverse Event (AE) was defined as any untoward medical occurrence in a participant administered an investigational product (IP) that does not necessarily have a causal relationship with the treatment. TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. TEAEs that were recorded as "possibly related" or "probably related" to HYQVIA were considered HYQVIA-related adverse events. Number of participants with any severe related TEAEs (excluding infections) was reported.

  From start of study drug administration up to 20 months

• Safety: Rate of Any Severe Related TEAEs Per Infusion (Excluding Infections)

  An AE was defined as any untoward medical occurrence in a participant administered an IP that does not necessarily have a causal relationship with the treatment. TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. TEAEs that were recorded as "possibly related" or "probably related" to HYQVIA were considered HYQVIA-related adverse events. Severe related TEAEs rate per infusion was calculated as number of severe related TEAEs/total number of infusions administered to participants in the analysis set. Rate of any severe related TEAEs per infusion (excluding infections) was reported.

  From start of study drug administration up to 20 months

• Safety: Number of Participants With Any Related Serious TEAEs Per Infusion (Excluding Infections)

  TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs that were recorded as "possibly related" or "probably related" to HYQVIA were considered HYQVIA-related adverse events. Number of participants with any related serious TEAEs per infusion (excluding infections) was reported.

  From start of study drug administration up to 20 months

• Safety: Rate of Any Related Serious TEAEs Per Infusion (Excluding Infections)

  TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in-patient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs that were recorded as "possibly related" or "probably related" to HYQVIA were considered HYQVIA-related adverse events. Rate of related serious TEAEs per infusion was calculated as number of related serious TEAEs/total number of infusions administered to participants in the analysis set. Rate of any related serious TEAEs per Infusion (excluding infections) was reported.

  From start of study drug administration up to 20 months

Secondary Outcomes (37)

• Efficacy: Change From Baseline in Total Serum Trough Levels of Immunoglobulin G (IgG) at Month 12

  Baseline, Month 12

• Efficacy: Change From Baseline in Serum Trough Levels of IgG Subclasses at Month 12

  Baseline, Month 12

• Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Clostridium Tetani Toxoid IgG at Month 12

  Baseline, Month 12

• Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Hepatitis B Virus (HBV) at Month 12

  Baseline, Month 12

• Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Haemophilus Influenzae B IgG at Month 12

  Baseline, Month 12

Study Arms (3)

EPOCH 1

EXPERIMENTAL

Ramp up period for participants who were not treated with HyQvia prior to this study

Biological: HYQVIA

EPOCH 2

EXPERIMENTAL

Participants who were treated with HyQvia prior to this study, and those who completed the ramp up period (Epoch 1). After one year in Epoch 2, participants with anti-rHuPH20 antibody titer \<160 at all time-points during the study will complete the study termination/completion visit at the next possible occasion. Participants with anti-rHuPH20 antibody titer \>=160 during the study and/or at the last measurement will continue for an additional two years of HyQvia treatment and observation.

Biological: HYQVIA

Epoch 3

EXPERIMENTAL

Safety follow-up for participants whose anti-rHuPH20 antibody titer was \>= 160 during Epoch 1 or Epoch 2 and who experience either a related serious adverse event (SAE) or a related severe adverse event (AE)

Biological: KIOVIG; Biological: Cuvitru

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

KIOVIG BIOLOGICAL

100 mg/ml solution for Immune Globulin Intravenous Infusion

Also known as: IGIV 10%, IGI 10%

Epoch 3

Cuvitru BIOLOGICAL

200 mg/ml solution for Immune Globulin Subcutaneous Injection

Also known as: IGSC 20%, IGI 20%

Epoch 3

Eligibility Criteria

• Age: 2 Years - 17 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 humoral immunodeficiency involving a defect in antibody formation and requiring gammaglobulin replacement, as defined according to the International Union of Immunological Societies (IUIS) Scientific Committee 2015 prior to enrollment. The diagnosis must be confirmed by the sponsor´s Medical Director prior to first treatment with investigational product (IP) in the study.
• Participant is at least two and below 18 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 body weight (BW)/four weeks and a maximum dose equivalent to 1000 mg/kg 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 amino transferase (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 (\< 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 \< 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 (20)

Fakultni nemocnice Brno Odd. Detska klinika

Brno, 61300, Czechia

Location

Fakultní nemocnice Hradec Králové

Nový Hradec Králové, 500 05, Czechia

Location

FN v Motole Interni klinika

Prague, 15006, Czechia

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Groupe Hospitalier Pellegrin - Hôpital des Enfants

Bordeaux, Gironde, 33076, France

Location

CHU Angers - Hôpital Hôtel Dieu

Angers, 49033, France

Location

Hospices Civils de Lyon - Hôpitaux Est - IHOP

Lyon, 69008, France

Location

Agia Sophia Children's Hospital

Athens, 115 27, Greece

Location

General Hospital of Thessaloniki Ippokrateio

Thessaloniki, 546 42, Greece

Location

General Hospital of Thessaloniki Papageorgiou

Thessaloniki, 564 03, Greece

Location

United St. Istvan and St. Laszlo Hospital

Budapest, H-1097, Hungary

Location

1.Detská klinika

Bratislava, 83340, Slovakia

Location

Univerzitna Nemocnica Klinika detí a dorastu

Martin, 03659, Slovakia

Location

Queen Silvia Children's Hospital

Gothenburg, 416 85, Sweden

Location

Dept. of Pediatric Oncology/Hematology/Immunology-Skånes Universitetssjukhus

Lund, 221 85, Sweden

Location

Bristol Royal Hospital for Children

Bristol, Avon, BS2 8BJ, United Kingdom

Location

Leeds Children's Hospital

Leeds, West Yorkshire, LS1 3EX, United Kingdom

Location

Royal Victoria Hospital

Belfast, BT1 6DW, United Kingdom

Location

University Hospital of Wales Heath Park Clinical Research Facility

Cardiff, CF14 4XW, United Kingdom

Location

The Great North Children's Hospital Royal Victoria Infirmary

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Related Publications (1)

• Ciznar P, Roderick M, Schneiderova H, Jesenak M, Krivan G, Brodszki N, Jolles S, Atisso C, Fielhauer K, Saeed-Khawaja S, McCoy B, Yel L. fSCIG 10% in pediatric primary immunodeficiency diseases: a European post-authorization safety study. Allergy Asthma Clin Immunol. 2024 Sep 17;20(1):47. doi: 10.1186/s13223-024-00904-9.

  PMID: 39289739 DERIVED

MeSH Terms

Conditions

Primary Immunodeficiency Diseases

Interventions

Hizentra

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: Shire

ClinicalTransparency@shire.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 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2017
• First Posted: April 17, 2017
• Study Start: May 30, 2017
• Primary Completion: January 15, 2021
• Study Completion: January 15, 2021
• Last Updated: January 11, 2023
• Results First Posted: January 11, 2023

Record last verified: 2022-04

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

CZ (3); GB (5); HU (1); GR (3); FR (3); SL (2); DK (1); SE (2)