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

Lead sponsor

Baxalta now part of Shire is the lead sponsor of 110 studies on the registry; none are open to participants now.

Of its 18 completed or terminated interventional studies of FDA-regulated products, 16 (89%) have results posted.

Study population

Groups and cohorts

• 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

• 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]

Interventions

• BiologicalA licensed human normal immunoglobulin other than HYQVIA for IV or SC infusion or an alternative treatment

  To be determined by the physician

• BiologicalHYQVIA [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase]

  Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase

  Also known as: Hyqvia

Primary outcomes

1. 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.

   Time frame: From start of study drug administration up to end of study (up to 48.4 months)

Secondary outcomes

1. 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.

   Time frame: From start of study drug administration up to end of study (up to 48.4 months)

2. 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.

   Time frame: From start of first mother enrollment up to last mother's completion/discontinuation of study (up to 29.1 months)

3. 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.

   Time frame: From start of first mother enrollment up to last mother's completion/discontinuation of study (up to 29.1 months)

4. 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.

   Time frame: Throughout the expectant mother pregnancy duration (up to 40 weeks)

5. Number of Participants Who Experienced General Pregnancy Outcomes

   Pregnancy outcomes included live birth, fetal death, termination or unknown.

   Time frame: Throughout the expectant mother pregnancy duration (up to 40 weeks)

6. 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.

   Time frame: At or after delivery/end of pregnancy (up to 40 weeks)

7. 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.

   Time frame: At or after delivery/end of pregnancy (up to 40 weeks)

8. 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.

   Time frame: At 6, 12, 18 and 24 months follow-up

9. 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.

   Time frame: At 6, 12, 18 and 24 months follow-up

Baseline characteristics

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. PubMed 35443783 ↗

Study documents

• Study protocol · Oct 22, 2015
• Statistical analysis plan · Apr 2, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — 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.

Supporting information: Study protocol, Sap, Icf, Csr