Pregnancy Registry to Collect Long-Term Safety Data From Women Treated With HyQvia

The purpose of this registry is to acquire safety data (including assessment of anti-rHuPH20 antibodies), regarding the course and outcome of pregnancy in women ever treated with HYQVIA. Development of the fetus/infant at birth and for the first 2 years will also be followed.

Study Overview

• Status: Completed
• Conditions: Exposure During Pregnancy
• Intervention / Treatment: Biological: A licensed human normal immunoglobulin other than HYQVIA for IV or SC infusion or an alternative treatment; Biological: HYQVIA [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase]

• Study Type: Observational
• Enrollment (Actual): 16

Contacts and Locations

Study Locations

• Czechia
  • Praha 10, Czechia, 10034
    • Fakultní Nemocnice Královské Vinohrady
• Germany
  • Baden-Württemberg
    • Freiburg, Baden-Württemberg, Germany, 79108
      • Freiburg University Hospital/ Prof. Dr. med. Bodo Grimbacher
  • Bayern
    • Würzburg, Bayern, Germany, 97080
      • Universitaetsklinikum Wuerzburg
  • Sachsen
    • Leipzig, Sachsen, Germany, 04129
      • Klinikum St. Georg GmbH
• Poland
  • Warszawa, Poland, 04-141
    • Wojskowy Instytut Medyczny
• Slovakia
  • Bratislava, Slovakia, 81250
    • Onkologicky ustav svatej Alzbety s.r.o.
  • Kosice, Slovakia, 04001
    • RAFMED s.r.o
• United States
  • North Carolina
    • Durham, North Carolina, United States, 27703
      • QuintilesIMS Plaza Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Women who became pregnant after ever treated with HYQVIA, and their infant children

Description

Inclusion Criteria:

• For the expectant mother only: Participant became pregnant during or after treatment with HYQVIA
• Participant/Participant's legally authorized representative is willing to sign an informed consent form (ICF)

Exclusion Criteria:

• There are no applicable Exclusion Criteria

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Alternative Product Arm; Participant stops HYQVIA treatment (if the participant is still treated) and a licensed human normal immunoglobulin other than HYQVIA for intravenous (IV) or subcutaneous (SC) infusion or an alternative treatment will be administered, as determined by the physician.	Biological: A licensed human normal immunoglobulin other than HYQVIA for IV or SC infusion or an alternative treatment; To be determined by the physician
HYQVIA Arm; Participant continues to receive HYQVIA (Immune Globulin (Human) 10% with recombinant human hyaluronidase (rHuPH20)), according to her treatment regimen.	Biological: HYQVIA [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase]; Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase; Other Names: Hyqvia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Serious Adverse Events (SAEs)	An Adverse Event (AE) was defined as any untoward medical occurrence in a participant administered a medicinal product that did not necessarily had a causal relationship with the treatment. A SAE was defined as an untoward medical occurrence that at any dose met one or more of the following criteria: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect, is an important medical event. Number of participants with SAEs in expectant mothers and infants were reported.	From start of study drug administration up to end of study (up to 48.4 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Non-serious Adverse Events (Non-SAEs), Related and Not Related to HyQvia/Human Normal Immunoglobulin (IG) or Alternative Treatment	An AE was defined as any untoward medical occurrence in a participant administered a medicinal product that did not necessarily have a causal relationship with the treatment. Number of participants with Non-SAEs, related and not related to HyQvia/Human Normal IG or alternative treatment in expectant mothers and infants were reported.	From start of study drug administration up to end of study (up to 48.4 months)
Number of Participants With Adverse Event of Special Interests (AESIs) in Expectant Mothers	AESI were AEs that were considered by the sponsor to be relevant for the monitoring of the safety profile. AESI's included in this study were local/immunologic AEs including skin changes (Such as, local erythema, local pruritus, induration, nodules). Number of participants with AESIs in expectant mother were reported.	From start of first mother enrollment up to last mother's completion/discontinuation of study (up to 29.1 months)
Number of Participants Who Developed Anti-rHuPH20 Antibodies in Expectant Mothers	Number of participants who developed positive [titer ≥160] of anti-rHuPH20 binding in expectant mothers were reported. Neutralizing antibodies were assessed if the binding antibody assay has a result of 160 or above.	From start of first mother enrollment up to last mother's completion/discontinuation of study (up to 29.1 months)
Number of Participants With Antenatal Diagnostic Procedures	Antenatal diagnostic procedures included ultrasound, serology and nuchal translucency screen which are used to assess the Fetal growth/development. Number of participants reported fetal growth/development were recorded.	Throughout the expectant mother pregnancy duration (up to 40 weeks)
Number of Participants Who Experienced General Pregnancy Outcomes	Pregnancy outcomes included live birth, fetal death, termination or unknown.	Throughout the expectant mother pregnancy duration (up to 40 weeks)
Number of Participants With Neonatal Assessment	Neonatal assessment included parameters like weight, length, head circumference, Apgar scores, pulse rate, blood pressure, respiratory rate, body temperature with normal, abnormal and missing status. The Apgar scores was determined by evaluating the newborn baby on five simple criteria: Appearance, Pulse, Grimace, Activity, Respiration: on a scale from zero to two, then summing up the five values thus obtained. The resulting Apgar score ranges from zero to 10. Zero is the worst possible score and 10 is the highest possible score.	At or after delivery/end of pregnancy (up to 40 weeks)
Number of Participants With Status of the Infant at Birth	Status of the infant at birth included the following as: Any need for resuscitation of the infant, Admission in intensive care unit, Presence of congenital malformations/anomaly, Any other conditions noted at or around birth with status yes, no and unknown.	At or after delivery/end of pregnancy (up to 40 weeks)
Number of Participants With Growth Measurement and Charts for the Infant	Growth measurement and charts for the infant was assessed based on following parameters: Any congenital malformations diagnosed that were not reported at birth, any conditions that were noted since birth, weight assessment, length assessment, head circumference assessment. Number of participants with growth measurement and charts for the infant at 6, 12, 18 and 24 months follow-up was reported.	At 6, 12, 18 and 24 months follow-up
Number of Participants With Development Milestones	Developmental milestones evaluation included rolled over, attended to and reached for objects, sat up without support, turned to locate a voice, said his/her first words, and stand without support/help. Number of participants with development milestones at 6, 12, 18 and 24 months follow-up was reported.	At 6, 12, 18 and 24 months follow-up

Collaborators and Investigators

• Sponsor: Baxalta now part of Shire
• Collaborators: Baxalta Innovations GmbH, now part of Shire

Publications and helpful links

General Publications

• Borte M, Raffac S, Hrubisko M, Jahnz-Rozyk K, Garcia E, McCoy B, Chavan S, Nagy A, Yel L. Long-term safety of facilitated subcutaneous immunoglobulin treatment in pregnant women with primary immunodeficiency diseases: results from a registry study. Immunotherapy. 2022 Jun;14(8):609-616. doi: 10.2217/imt-2021-0336. Epub 2022 Apr 20.

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2015
• Primary Completion (Actual): December 17, 2019
• Study Completion (Actual): December 17, 2019

Study Registration Dates

• First Submitted: June 26, 2015
• First Submitted That Met QC Criteria: September 21, 2015
• First Posted (Estimate): September 22, 2015

Study Record Updates

• Last Update Posted (Actual): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 2, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: 161301; EUPAS5798 (Registry Identifier: EU PAS Register)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR