Primary Immunodeficiency Diseases (PID)Phase 4NCT03116347
Post-Authorization Safety, Tolerability and Immunogenicity Evaluation of HyQvia in Pediatric PIDD Subjects
A Phase 4 study testing HYQVIA, KIOVIG and Cuvitru in people with Primary Immunodeficiency Diseases (PID), run by Baxalta now part of Shire at 20 sites in 8 countries.
Trial 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) Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Primary Immunodeficiency Diseases (PID)
- What is being tested?
- HYQVIA, KIOVIG and Cuvitru
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 20 sitesin 8 countries
- Study dates
- 30 May 2017to 15 Jan 2021
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
20 sites in 8 countries.
20 sites in 8 countries
United Kingdom5 sites
Royal Victoria Hospital
Belfast, BT1 6DW
Bristol Royal Hospital for Children
Bristol, Avon, BS2 8BJ
University Hospital of Wales Heath Park Clinical Research Facility
Cardiff, CF14 4XW
Leeds Children's Hospital
Leeds, West Yorkshire, LS1 3EX
The Great North Children's Hospital Royal Victoria Infirmary
Newcastle upon Tyne, NE7 7DN
Czechia3 sites
Fakultni nemocnice Brno Odd. Detska klinika
Brno, 61300
Fakultní nemocnice Hradec Králové
Nový Hradec Králové, 500 05
FN v Motole Interni klinika
Prague, 15006
France3 sites
CHU Angers - Hôpital Hôtel Dieu
Angers, 49033
Groupe Hospitalier Pellegrin - Hôpital des Enfants
Bordeaux, Gironde, 33076
Hospices Civils de Lyon - Hôpitaux Est - IHOP
Lyon, 69008
Greece3 sites
Agia Sophia Children's Hospital
Athens, 115 27
General Hospital of Thessaloniki Ippokrateio
Thessaloniki, 546 42
General Hospital of Thessaloniki Papageorgiou
Thessaloniki, 564 03
Slovakia2 sites
1.Detská klinika
Bratislava, 83340
Univerzitna Nemocnica Klinika detí a dorastu
Martin, 03659
Sweden2 sites
Queen Silvia Children's Hospital
Gothenburg, 416 85
Dept. of Pediatric Oncology/Hematology/Immunology-Skånes Universitetssjukhus
Lund, 221 85
About this study
Official title: Post-Authorization Safety, Tolerability and Immunogenicity Evaluation of HyQvia in Pediatric Subjects With Primary Immunodeficiency Diseases
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)
- Being tested
- HYQVIA, KIOVIG, Cuvitru
- Medical subject headings
- Primary Immunodeficiency Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HYQVIABiological
Also called IGI 10% with rHuPH20
Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase (IGI, 10% with rHuPH20)
KIOVIGBiological
Also called IGIV 10%, IGI 10%
100 mg/ml solution for Immune Globulin Intravenous Infusion
CuvitruBiological
Also called IGSC 20%, IGI 20%
200 mg/ml solution for Immune Globulin Subcutaneous Injection
| Study group | Role | What they receive |
|---|---|---|
| EPOCH 1 | Experimental | Ramp up period for participants who were not treated with HyQvia prior to this study Receives: 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. Receives: 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) Receives: Biological: KIOVIG; Biological: Cuvitru |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Change from baseline in total serum trough levels of IgG in Epoch 1 and 2 was reported. Baseline was defined as the last non-missing value before the initial dose of HYQVIA.
Measured: Baseline, Month 12
Efficacy: Change From Baseline in Serum Trough Levels of IgG Subclasses at Month 12
Change from baseline in Serum trough levels of IgG subclasses 1, 2, 3, and 4 in Epoch 1 and 2 was reported. Baseline was defined as the last non-missing value before the initial dose of HYQVIA.
Measured: Baseline, Month 12
Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Clostridium Tetani Toxoid IgG at Month 12
Change from baseline in trough levels of specific antibodies in clostridium tetani toxoid IgG at Month 12 was reported. Baseline was defined as the last non-missing value before the initial dose of HYQVIA. Here, IU/ml was defined as "International units per milliliter".
Measured: Baseline, Month 12
Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Hepatitis B Virus (HBV) at Month 12
Change from baseline in trough levels of specific antibodies in HBV at Month 12 was reported. Baseline was defined as the last non-missing value before the initial dose of HYQVIA.
Measured: Baseline, Month 12
Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Haemophilus Influenzae B IgG at Month 12
Change from baseline in trough levels of specific antibodies in Haemophilus influenzae B IgG at Month 12 was reported. Baseline was defined as the last non-missing value before the initial dose of HYQVIA.
Measured: Baseline, Month 12
Safety: Percentage of Participants Who Achieved a Treatment Interval of Three or Four Weeks in Epoch 2
Percentage of participants who achieved a treatment interval of three or four weeks in Epoch 2 was reported.
Measured: Up to 20 months
Safety: Percentage of Participants Who Maintained a Treatment Interval of Three or Four Weeks in Epoch 2 up to 12 Months
Percentage of participants who maintained a treatment interval of three or four weeks in Epoch 2 up to 12 months was reported.
Measured: Up to 12 months
Safety: Number of Participants With Local TEAEs (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. Number of Participants with local TEAEs (excluding infections) was reported.
Measured: From start of study drug administration up to 20 months
Safety: Rate of Local TEAEs Per Infusion (Excluding Infections)
Rate of local TEAEs per infusion was calculated as number of local adverse events/total number of infusions administered to participants in the analysis set. Only events are included which start prior to participants start date of non-response. Rate of local TEAEs per infusion (excluding infections) was reported.
Measured: From start of study drug administration up to 20 months
Safety: Number of Participants With Local Adverse Reaction (Excluding Infections)
Adverse reaction was defined as any TEAE that meets any of the following criteria: 1) A TEAE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or; 2) A TEAE that begins during infusion of IP or within 72 hours following the end of IP infusion, or; 3) A TEAE for which causality assessment is missing or indeterminate. Number of participants with local adverse reactions (excluding infections) was reported.
Measured: From start of study drug administration up to 20 months
Safety: Rate of Local Adverse Reaction Per Infusion (Excluding Infections)
Rate of local adverse reaction per infusion was calculated as number of local adverse reaction events/total number of infusions administered to participants in the analysis set. Rate of local adverse reactions per infusion (excluding infections) was reported.
Measured: From start of study drug administration up to 20 months
Safety: Number of Participants With Systemic TEAEs (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. Number of participants with systemic TEAEs (excluding infections) was reported..
Measured: From start of study drug administration up to 20 months
Safety: Rate of Systemic TEAEs Per Infusion (Excluding Infections)
Rate of systemic TEAEs per infusion was calculated as number of systemic adverse events/total number of infusions administered to participants in the analysis set. Rate of systemic TEAEs per infusion was assessed based on events per infusion.
Measured: From start of study drug administration up to 20 months
Safety: Number of Participants With Systemic Adverse Reaction (Excluding Infections)
Adverse reaction was defined as any TEAE that meets any of the following criteria: 1) A TEAE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or; 2) A TEAE that begins during infusion of IP or within 72 hours following the end of IP infusion, or; 3) A TEAE for which causality assessment is missing or indeterminate. Number of participants with systemic adverse reaction (excluding infections) was reported.
Measured: From start of study drug administration up to 20 months
Safety: Rate of Systemic Adverse Reaction Per Infusion (Excluding Infections)
Rate of Systemic adverse reactions per infusion was calculated as number of systemic adverse reaction events/total number of infusions administered to participants in the analysis set. Rate of systemic adverse reactions per infusion (excluding infections) was reported.
Measured: From start of study drug administration up to 20 months
Safety: Number of Participants With Any TEAEs (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. Number of participants with any TEAEs (excluding infections) was reported.
Measured: From start of study drug administration up to 20 months
Safety: Rate of TEAEs Per Infusion (Excluding Infections)
Rate of TEAEs per infusion was calculated as number of adverse events/total number of infusions administered to participants in the analysis set. Rate of TEAEs per infusion (excluding infections) was reported.
Measured: From start of study drug administration up to 20 months
Safety: Number of Participants With Any Adverse Reactions (Excluding Infections)
Adverse reaction was defined as any TEAE that meets any of the following criteria: 1) A TEAE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or; 2) A TEAE that begins during infusion of IP or within 72 hours following the end of IP infusion, or; 3) A TEAE for which causality assessment is missing or indeterminate. Number of participants with any adverse reactions (excluding infections) was reported.
Measured: From start of study drug administration up to 20 months
Safety: Rate of Any Adverse Reaction Per Infusion (Excluding Infections)
Rate of all adverse reactions per infusion was calculated as number of adverse reaction events/total number of infusions administered to participants in the analysis set. Rate of any adverse reactions per infusion (excluding infections) was reported.
Measured: From start of study drug administration up to 20 months
Safety: Number of Participants With Any Temporally Associated TEAEs (Excluding Infections)
Temporally-associated TEAEs were defined as TEAEs which begin during infusion of IP or within 72 hours following the end of IP infusion. Number of participants with any temporally associated TEAEs (excluding infections) was reported.
Measured: From start of study drug administration up to 20 months
Safety: Rate of Any Temporally Associated TEAEs Per Infusion (Excluding Infections)
Rate of any temporally associated TEAEs per infusion was calculated as number of temporally associated adverse events/total number of infusions administered to participants in the analysis set. Temporally-associated TEAEs were defined as TEAEs which begin during infusion of IP or within 72 hours following the end of IP infusion. Rate of any temporally associated TEAEs per infusion (excluding infections) was reported.
Measured: From start of study drug administration up to 20 months
Safety: Number of Participants With Any Related (Causally) and/or Temporally Associated TEAEs (Excluding Infections)
Number of participants with any related (causally) and/or temporally associated TEAEs (excluding infections) was reported. Temporally-associated TEAEs were defined as TEAEs which begin during infusion of IP or within 72 hours following the end of IP infusion.
Measured: From start of study drug administration up to 20 months
Safety: Rate of Any Related (Causally) and/or Temporally Associated TEAEs Per Infusion (Excluding Infections)
Rate of any related (causally) and/or temporally associated TEAEs per infusion was calculated as number of related and/or temporally associated adverse events/ total number of infusions administered to participants in the analysis set. TEAEs recorded in the study database as "possibly related" or "probably related" to HYQVIA are considered HYQVIA-related adverse events. Temporally-associated TEAEs were defined as TEAEs which begin during infusion of IP or within 72 hours following the end of IP infusion. Rate of any related (causally) and/or temporally associated TEAEs per infusion (excluding infections) was reported.
Measured: From start of study drug administration up to 20 months
Safety: Number of Participants With Any Serious TEAEs (Excluding Infections)
Serious TEAE were the AEs 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. Number of participants with any serious TEAEs (excluding infections) was reported.
Measured: From start of study drug administration up to 20 months
Safety: Rate of Serious TEAEs Per Infusion (Excluding Infections)
Rate of serious TEAEs per infusion was calculated as number of serious adverse events/total number of infusions administered to participants in the analysis set. Rate of serious TEAEs per infusion (excluding infections) was reported.
Measured: From start of study drug administration up to 20 months
Safety: Number of Participants Who Developed Positive Titer (>=160) of Binding or Neutralizing Antibodies to rHuPH20
Number of participants who developed positive titer (>=160) of binding or neutralizing antibodies to rHuPH20 was reported.
Measured: From start of study drug administration up to 20 months
Other Analysis: Number of Infusions Per Month
Number of infusions per month was calculated as total number of infusions per duration of treatment (days) * 30.4 days per month.
Measured: Up to 20 months
Other Analysis: Number of Infusion Sites (Needle-Sticks) Per Infusion
Number of infusion sites (needle-sticks) per infusion was calculated as total number of infusion sites / total number of infusions. Only infusions with complete data available were included.
Measured: Up to 20 months
Other Analysis: Number of Infusion Sites (Needle-Sticks) Per Month
Number of infusion sites per month was calculated as total number of infusion sites / duration of treatment (days) * 30.4 days. Only infusions with complete data available were included.
Measured: Up to 20 months
Other Analysis: Duration of Infusion
The duration of infusion was defined as the difference between the end time and the start time of the HyQvia infusion.
Measured: From start of study drug administration up to 20 months.
Other Analysis: Maximum Infusion Rate Per Site
Maximum infusion rate per site was reported.
Measured: Up to 20 months
Other Analysis: Infusion Volume Per Site
Infusion volume per site was calculated as actual IgG volume (milliliter [mL]) / total number of infusion sites (hour) used.
Measured: Up to 20 months
Other Analysis: Number of Infusions That Were Interrupted or Stopped Due to an AE
Number of infusions that were interrupted or Stopped due to an AE was reported.
Measured: Up to 20 months
Other Analysis: Number of Weeks to Reach Final 3 or 4-week Dose Interval in Epoch 1
Final dose interval, defined as three or four weeks infusion interval in Epoch 1 of treatment period, was reported.
Measured: Up to 20 months
Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL)
PedsQL Generic Core Scale (GCS) was used for QOL assessment. It encompasses 4 dimensions (physical functioning [PF], emotional functioning [EF], social functioning [SF], school functioning [ScF]). Age groups are: Toddler (2-4 years), Young child (5-7 years), Child (8-12 years), and Teens (13-<18 years). Depending on the participants age, the questionnaire may be completed by either the participant or the parent/caregiver as appropriate. For the Toddler group, the PedsQL GCS consisted of 21 items, using a 5-point Likert scale (0 to 4); for all other groups, the PedsQL consisted of 23 items, with a 3-point Likert scale (0, 2, 4) for the young child, and a 5-point Likert scale for the child and teens groups. All Scores were transformed on a scale from 0 to 100 where 0=100, 1=75, 2=50, 3=25, and 4=0. Higher scores indicate better quality of life. A negative change from baseline indicates worse quality of life. Baseline: last non-missing value before the initial dose of HYQVIA.
Measured: Baseline up to 20 months
HRQoL: Change From Baseline in EuroQoL (Quality of Life)-5 Dimensions (EQ-5D)
EQ-5D considered five attributes of quality of life evaluation, that is, mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. Each dimension had five possible levels: 1 (no problems); 2 (slight problems); 3 (moderate problems); 4 (severe problems), and; 5 (extreme problems). The participants rating of their current HRQoL state was recorded using a standard vertical 20-cm visual analog scale (EQ-VAS), which ranged from 0 to 100, where 0 indicated worst imaginable health state and 100 was best imaginable health state. Baseline was defined as the last non-missing value before the initial dose of HYQVIA. A negative change from baseline indicates worse health state.
Measured: Baseline up to 20 months
HR QoL: Change From Baseline in Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9)
TSQM-9 is a 9-item, validated, self-administered instrument to assess participants satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. The scores were computed by adding items for each domain, i.e. 1 to 3 for effectiveness, 4 - 6 for convenience and 7 to 9 for global satisfaction. The lowest possible score (1 for each item and 3 for all 3 subscales) was subtracted from the composite score and divided by the greatest possible score range. The greatest range was (7-1)*3 items = 18 for the effectiveness and convenience, and (5-1)*3 items = 12 for global satisfaction . The item scores of each of the 3 domains are summed and transformed to create a score of 0 (extremely dissatisfied) to 100 (extremely satisfied). Higher score indicated greater satisfaction in that domain. A negative change from baseline indicates less satisfaction in that domain. Baseline was defined as the last non-missing value before the initial dose of HYQVIA.
Measured: Baseline up to 20 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2017
- Study start30 May 2017
- Primary completion15 Jan 2021
- Study completion15 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary Immunodeficiency Diseases (PID)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baxalta now part of Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Baxalta Innovations GmbH, now part of Shire
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Shire
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03116347
- Sponsor's protocol ID
- 161504
- Other IDs
- 2016-003438-26, 2016
- Status last verified
- Apr 2022
- First submitted
- 12 Apr 2017
- Last updated
- 11 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
Publications
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.
PubMed 39289739
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Post-Authorization Safety, Tolerability and Immunogenicity Evaluation of HyQvia in Pediatric Subjects With Primary Immunodeficiency Diseases
- ClinicalTrials.gov ID
- NCT03116347
- Acronym / sponsor ID
- 161504
- Conditions
- Primary Immunodeficiency Diseases (PID)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Baxalta now part of ShireIndustry (pharma, biotech, devices)
- Collaborators
- Baxalta Innovations GmbH, now part of Shire
- Study start
- 30 May 2017 (actual)
- Primary completion
- 15 Jan 2021 (actual)
- Study completion
- 15 Jan 2021 (actual)
- First posted
- 17 Apr 2017 (actual)
- Results
- Posted 11 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| EPOCH 1 | Experimental | Biological: HYQVIARamp up period for participants who were not treated with HyQvia prior to this study |
| EPOCH 2 | Experimental | Biological: HYQVIAParticipants 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. |
| Epoch 3 | Experimental | Biological: KIOVIG, Biological: CuvitruSafety 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) |
Who may qualify
- Ages
- 2 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (14 listed)
- 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):
- 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. .
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HYQVIAAlso: IGI 10% with rHuPH20Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase (IGI, 10% with rHuPH20) | Biological | EPOCH 1, EPOCH 2 |
| KIOVIGAlso: IGIV 10%, IGI 10%100 mg/ml solution for Immune Globulin Intravenous Infusion | Biological | Epoch 3 |
| CuvitruAlso: IGSC 20%, IGI 20%200 mg/ml solution for Immune Globulin Subcutaneous Injection | Biological | Epoch 3 |
Primary outcome
Safety: Number of Participants With Any Severe Related Treatment-emergent Adverse Events (TEAEs) Per Infusion (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
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.
Safety: Rate of Any Severe Related TEAEs Per Infusion (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
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.
Safety: Number of Participants With Any Related Serious TEAEs Per Infusion (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
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.
Safety: Rate of Any Related Serious TEAEs Per Infusion (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
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.
37 secondary outcomes
Efficacy: Change From Baseline in Total Serum Trough Levels of Immunoglobulin G (IgG) at Month 12
Time frame: Baseline, Month 12
Efficacy: Change From Baseline in Serum Trough Levels of IgG Subclasses at Month 12
Time frame: Baseline, Month 12
Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Clostridium Tetani Toxoid IgG at Month 12
Time frame: Baseline, Month 12
Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Hepatitis B Virus (HBV) at Month 12
Time frame: Baseline, Month 12
Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Haemophilus Influenzae B IgG at Month 12
Time frame: Baseline, Month 12
Safety: Percentage of Participants Who Achieved a Treatment Interval of Three or Four Weeks in Epoch 2
Time frame: Up to 20 months
Safety: Percentage of Participants Who Maintained a Treatment Interval of Three or Four Weeks in Epoch 2 up to 12 Months
Time frame: Up to 12 months
Safety: Number of Participants With Local TEAEs (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
Safety: Rate of Local TEAEs Per Infusion (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
Safety: Number of Participants With Local Adverse Reaction (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
Safety: Rate of Local Adverse Reaction Per Infusion (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
Safety: Number of Participants With Systemic TEAEs (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
Safety: Rate of Systemic TEAEs Per Infusion (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
Safety: Number of Participants With Systemic Adverse Reaction (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
Safety: Rate of Systemic Adverse Reaction Per Infusion (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
Safety: Number of Participants With Any TEAEs (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
Safety: Rate of TEAEs Per Infusion (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
Safety: Number of Participants With Any Adverse Reactions (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
Safety: Rate of Any Adverse Reaction Per Infusion (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
Safety: Number of Participants With Any Temporally Associated TEAEs (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
Safety: Rate of Any Temporally Associated TEAEs Per Infusion (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
Safety: Number of Participants With Any Related (Causally) and/or Temporally Associated TEAEs (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
Safety: Rate of Any Related (Causally) and/or Temporally Associated TEAEs Per Infusion (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
Safety: Number of Participants With Any Serious TEAEs (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
Safety: Rate of Serious TEAEs Per Infusion (Excluding Infections)
Time frame: From start of study drug administration up to 20 months
Safety: Number of Participants Who Developed Positive Titer (>=160) of Binding or Neutralizing Antibodies to rHuPH20
Time frame: From start of study drug administration up to 20 months
Other Analysis: Number of Infusions Per Month
Time frame: Up to 20 months
Other Analysis: Number of Infusion Sites (Needle-Sticks) Per Infusion
Time frame: Up to 20 months
Other Analysis: Number of Infusion Sites (Needle-Sticks) Per Month
Time frame: Up to 20 months
Other Analysis: Duration of Infusion
Time frame: From start of study drug administration up to 20 months.
Other Analysis: Maximum Infusion Rate Per Site
Time frame: Up to 20 months
Other Analysis: Infusion Volume Per Site
Time frame: Up to 20 months
Other Analysis: Number of Infusions That Were Interrupted or Stopped Due to an AE
Time frame: Up to 20 months
Other Analysis: Number of Weeks to Reach Final 3 or 4-week Dose Interval in Epoch 1
Time frame: Up to 20 months
Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL)
Time frame: Baseline up to 20 months
HRQoL: Change From Baseline in EuroQoL (Quality of Life)-5 Dimensions (EQ-5D)
Time frame: Baseline up to 20 months
HR QoL: Change From Baseline in Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9)
Time frame: Baseline up to 20 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39289739Ciznar 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.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Shire
20 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing HYQVIA, KIOVIG and Cuvitru in people with Primary Immunodeficiency Diseases (PID), run by Baxalta now part of Shire at 20 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United Kingdom, Czechia, France, Greece, Slovakia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety: Number of Participants With Any Severe Related Treatment-emergent Adverse Events (TEAEs) Per Infusion (Excluding Infections) (time frame: From start of study drug administration up to 20 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03116347, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2023.