Primary Immunodeficiency Diseases (PID)Phase 3NCT04346108
A Study of Immune Globulin Subcutaneous (Human), 20% Solution (IGSC, 20%) in Japanese Participants With Primary Immunodeficiency Diseases (PID)
A Phase 3 study testing Immune Globulin Intravenous (IGIV) and Immune Globulin Subcutaneous, 20% Solution (IGSC, 20%) in people with Primary Immunodeficiency Diseases (PID), run by Baxalta now part of Shire at 8 sites in Japan.
Trial summary
In this study, Japanese participants with primary immunodeficiency diseases were treated with Immune Globulin Subcutaneous (Human), 20% solution, (IGSC, 20%). This study will be in 3 parts: Part 1: Infusions with Immunoglobulin Intravenous (IGIV) every 3 or 4 weeks for 13 weeks. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Primary Immunodeficiency Diseases (PID)
- What is being tested?
- Immune Globulin Intravenous (IGIV) and Immune Globulin Subcutaneous, 20% Solution (IGSC, 20%)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 8 sitesJapan
- Study dates
- 11 Aug 2020to 22 Dec 2021
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Be of Japanese descent, defined as born in Japan and having Japanese parents and Japanese maternal and paternal grandparents.
- Participants must have a documented diagnosis of a form of primary humoral immunodeficiency involving antibody formation and requiring gammaglobulin replacement. The diagnosis must be confirmed by the medical director prior to treatment with IGIV.
- Participant is 2 years or older at the time of screening.
- Written informed consent is obtained from either the participants or the participants legally authorized representative prior to any study-related procedures and study product administration.
- Participant has been receiving a consistent dose of IGIV over a period of at least 3 months prior to screening equivalent to approximately 200-600 mg/kg-body weight (BW) per 3- 4 week period, as according to the product package insert
- Participant has a serum trough level of IgG >= 5 gram per liter (g/L) at screening.
- Participant has not had a serious bacterial infection within the 3 months prior to screening.
- Participant 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/milli cubic meter [mm^3]).
- Participant has presence of renal function impairment defined by estimated glomerular filtration rate (eGFR) is <60 milliliter per minute/ 1.73 square meter (mL/min/1.73m^2).
- Participant has been diagnosed with or has a malignancy (other than adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix), unless the disease-free period prior to screening exceeds 5 years.
Show all 23Show fewer
- Participant is receiving anti-coagulation therapy or has a history of thrombotic episodes (including deep vein thrombosis, myocardial infarction, cerebrovascular accident, pulmonary embolism) within 12 months prior to screening or a history of thrombophilia.
- Participant has abnormal protein loss (protein losing enteropathy, nephrotic syndrome).
- 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 IV immunoglobulin, SC immunoglobulin, and/or Immune Serum Globulin (ISG) infusions.
- Participant has immunoglobulin A (IgA) deficiency (IgA less than 0.07 g/L), known anti IgA antibodies, and a history of hypersensitivity.
- Participant is on preventative (prophylactic) systemic antibacterial antibiotics at doses sufficient to treat or prevent bacterial infections, and cannot stop these antibiotics at the time of screening.
- 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/ microliter (mcL), or, in the opinion of the investigator, would be at significant risk of increased bleeding or bruising as a result of subcutaneous therapy.
- Participant has total protein > 9 gram per deciliter (g/dL) or myeloma, or macroglobulinemia (IgM) or paraproteinemia.
- Women of childbearing potential meeting any one of the following criteria:
- Participant presents with a positive pregnancy test.
- Participant is breast feeding.
- Participant intends to begin nursing during the course of the study.
- Participant does not agree to employ adequate birth-control measures (e.g. intrauterine device, diaphragm or condom [for male partner] with spermicidal jelly or foam, or birth control pills/patches) throughout the course of the study.
- Participant has participated in another clinical study and has been exposed to an IP or device within 30 days prior to study enrollment.
- Participant is scheduled to participate in another non-observational (interventional) clinical study involving an IP or device during the course of the study.
- Participant has severe dermatitis that would preclude adequate sites for safe product administration.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Japan8 sites
Tokyo Medical Dental University Hospital
Bunkyo-ku, Tokyo, 113-8519
Kyushu University Hospital
Fukuoka, Fukuoka, 812-8582
Gifu University Hospital
Gifu, Gifu, 501-1194
Hiroshima University Hospital
Hiroshima, Hiroshima, 734-8551
Kanazawa University Hospital
Kanazawa, Ishikawa-ken, 920-8641
Kurume University Hospital
Kurume-shi, Fukuoka, 830-0011
Nagoya University Hospital
Nagoya, Aichi-ken, 466-8560
National Defense Medical College Hospital
Tokorozawa-shi, Saitama, 359-8513
About this study
Official title: A Phase 3, Open-label, Non-controlled, Multi-dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability, and Efficacy of Immune Globulin Subcutaneous (Human), 20% Solution (IGSC, 20%) in Japanese Subjects With Primary Immunodeficiency Diseases (PID)
In this study, Japanese participants with primary immunodeficiency diseases were treated with Immune Globulin Subcutaneous (Human), 20% solution, (IGSC, 20%). This study will be in 3 parts:
Part 1: Infusions with Immunoglobulin Intravenous (IGIV) every 3 or 4 weeks for 13 weeks.
Read more
Part 2: Participants will switch to weekly subcutaneous infusions with IGSC, 20% for 24 weeks.
Part 3: A subset will receive biweekly subcutaneous infusions with IGSC, 20% for 12 weeks.
The main aim of the study is to assess base levels of Immunoglobulin globulin G (IgG) levels in the blood of the participants after weekly and biweekly treatment with IGSC, 20% (in Parts 2 and 3 of the study). Their PID will be treated by their doctor according to their doctor's usual clinical practice.
Read the detailed description
This study consists of 3 treatment parts (Epoch 1, 2, 3). The total evaluation period of the study will be 57 weeks in which screening period is for 2-8 weeks and Epoch 1 is from Week 8 to Week 21, Epoch 2 is from Week 21 to Week 45, Epoch 3 is from Week 45 to Week 57.
Each participant will receive IGIV treatment in Epoch 1 for a total of 13 weeks, then switch to weekly subcutaneous (SC) treatment with IGSC, 20% in Epoch 2 for a total of 24 weeks and will continue into Epoch 3 for a total of 12 weeks of biweekly SC treatment with IGSC, 20%. Drug dose in Epoch 2 and Epoch 3 will be adjusted so that it will be an equivalent weekly dose of the dose administered in Epoch 1 and twice the dose administrated in Epoch 2 respectively. Epoch 2 will contain two periods, period 1: dose adjustment period (first 12 weeks) and period 2: evaluation period (second 12 weeks).
- Conditions
- Primary Immunodeficiency Diseases (PID)
- Being tested
- Immune Globulin Intravenous (IGIV), Immune Globulin Subcutaneous, 20% Solution (IGSC, 20%)
- 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.
Immune Globulin Intravenous (IGIV)Biological
Also called Immune Globulin Infusion (Human)
Participants will receive IGIV infusion.
Immune Globulin Subcutaneous, 20% Solution (IGSC, 20%)Biological
Also called Immune Globulin Infusion (Human)
Participants will receive IGSC, 20% SC infusion.
| Study group | Role | What they receive |
|---|---|---|
| Epoch 1: IGIV 200-600 mg/kg | Experimental | Participants received 200 to 600 mg/kg of Immunoglobulin Intravenous (IGIV) infusion for every 3 or 4 weeks for up to 13 weeks. Receives: Biological: Immune Globulin Intravenous (IGIV) |
| Epoch 2: IGSC (20%) 50-200 mg/kg | Experimental | Participants who entered to Epoch 2 from Epoch 1 received 50-200 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion once a week up to approximately 24 weeks after Epoch 1. Receives: Biological: Immune Globulin Subcutaneous, 20% Solution (IGSC, 20%) |
| Epoch 3: IGSC (20%) 100-400 mg/kg | Experimental | Participants who entered to Epoch 3 from Epoch 1 received 100-400 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion biweekly up to approximately 12 weeks after Epoch 2. Receives: Biological: Immune Globulin Subcutaneous, 20% Solution (IGSC, 20%) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Epoch 2: Total Serum Trough Levels of Immune Globulin G (IgG) Antibodies During Period 2
Total serum trough levels of IgG antibodies measured during period 2 of Epoch 2 were assessed.
Measured: Epoch 2 (period 2): Up to 24 weeks
Epoch 3: Total Serum Trough Levels of IgG Antibodies
Total serum trough levels of IgG antibodies measured during Epoch 3 were assessed.
Measured: Epoch 3: Up to Week 12
Secondary outcomes (28)
Epoch 1: Total Serum Trough Levels of IgG Antibodies
Total serum trough levels of IgG antibodies measured during Epoch 1 were assessed.
Measured: Epoch 1: Up to Week 13
Epoch 2: Area Under the Curve From Time 0 to Last Interval (AUC0-last) for Total Serum Levels of IgG
Measured: Epoch 2: Week 21
Epoch 2: AUC0-last for Total Serum Levels of IgG Subclasses
Total serum levels of IgG subclasses IgG 1, IgG 2, IgG 3, and IgG 4 were determined.
Measured: Epoch 2: Week 21
Epoch 2: Apparent Clearance (CL/F) for Total Serum Levels of IgG
Measured: Epoch 2: Week 21
Epoch 2: CL/F for Total Serum Levels of IgG Subclasses
Total serum levels of IgG subclasses IgG 1, IgG 2, IgG 3, and IgG 4 were determined.
Measured: Epoch 2: Week 21
Epoch 2: Maximum Concentration (Cmax) for Total Serum Levels of IgG
Measured: Epoch 2: Week 21
Epoch 2: Cmax for Total Serum Levels of IgG Subclasses
Total serum levels of IgG subclasses IgG 1, IgG 2, IgG 3, and IgG 4 were determined.
Measured: Epoch 2: Week 21
Epoch 2: Minimum Concentration (Cmin) for Total Serum Levels of IgG
Measured: Epoch 2: Week 21
Epoch 2: Cmin for Total Serum Levels of IgG Subclasses
Total serum levels of IgG subclasses IgG 1, IgG 2, IgG 3, and IgG 4 were determined.
Measured: Epoch 2: Week 21
Epoch 2: Time to Maximum Concentration (Tmax) for Total Serum Levels of IgG
Measured: Epoch 2: Week 21
Epoch 2: Tmax for Total Serum Levels of IgG Subclasses
Total serum levels of IgG subclasses IgG 1, IgG 2, IgG 3, and IgG 4 were determined.
Measured: Epoch 2: Week 21
Trough Levels of Specific Antibodies to Clinically Relevant Pathogens: Clostridium Tetani Toxoid and Hepatitis B Virus (HBV)
Trough levels of specific antibodies to clinically relevant pathogen (Clostridium tetani toxoid and HBV) were assessed in Epoch 1, Epoch 2 and Epoch 3. Data was analyzed per interval in each Epoch for this outcome measure.
Measured: Epoch 1 (Week 1); Epoch 2 (Week 1, 24); Epoch 3 (Week 1, 13)
Trough Levels of Specific Antibodies to Clinically Relevant Pathogen: Haemophilus Influenzae (HIB)
Trough levels of specific antibodies to clinically relevant pathogens (HIB) were assessed in Epoch 1, Epoch 2, and Epoch 3. Data was analyzed per interval in each Epoch for this outcome measure.
Measured: Epoch 1 (Week 1); Epoch 2 (Week 1, 24); Epoch 3 (Week 1, 13)
Health Related Quality of Life: Treatment Preference
Treatment preference questionnaire is a self-administered questionnaire developed to assess participants' preference towards the administration of new IGSC therapy. There are 4-items on the questionnaire, which investigate a participant's preference on the clinic/hospital/home setting of receiving the immunoglobulin therapy, the participant's rating on the frequency and method of administration, and the participant's preference to continue receiving the IGSC treatment. The questionnaire included following categories: Where do you prefer to receive your immunoglobulin therapy, The frequency of administration, as pre-specified in protocol, data is reported as per age (2-13 years and >=14 years).
Measured: Up to approximately 1.5 years
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
TEAEs was defined as adverse events (AEs) with onset after date-time of first dose of study drug, or medical conditions present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. Any TEAE that is recorded by the investigator as "possibly related" or "probably related" to IP was considered as IGSC, 20%-related AE, and any AE recorded as "unlikely related" or "not related" was considered as unrelated AE. AEs included vital signs, clinical laboratory measurements.
Measured: From first dose of study drug up to end of study (up to approximately 1.5 years)
Number of Participants With Tolerability Events Related to the Infusion of Study Drug
An infusion is considered tolerable if the infusion rate was not reduced, or the infusion was not interrupted or stopped, due to TEAE related to study drug (IGIV or IGSC) infusion. A tolerability event is considered to have occurred if an infusion was not tolerable in Epoch 1, Epoch 2 and Epoch 3. Number of participants with tolerability events related to infusion of IP were assessed.
Measured: From first dose of study drug up to end of study (up to approximately 1.5 years)
Annual Rate of Validated Acute Serious Bacterial Infections (ASBI)
The ASBI rate was calculated as the mean number of acute serious bacterial infections per participants per year. Annual rate of validated acute serious bacterial infections per participant was assessed.
Measured: From first dose of study drug up to end of study (up to approximately 1.5 years)
Annual Rate of All Infections Per Year
Annual rate is the number of participants reporting any infection per year.
Measured: From first dose of study drug up to end of study (up to approximately 1.5 years)
Number of Days Participants Not Able to Attend School or Work to Perform Normal Daily Activities Due to Illness/Infection
Number of days not able to attend school or work to perform normal daily activities due to illness/infection are standardized per year (365.25 days). The number of days not able to attend school or work to perform normal daily activities due to illness/infection were assessed.
Measured: From first dose of study drug up to end of study (up to approximately 1.5 years)
Number of Days Participants Were on Antibiotics
Number of days on antibiotics is defined as the number of days those antibiotics were taken as concomitant medications and is standardized to per year (365.25 days). Antibiotics are defined as any medication under anatomical therapeutic chemical Level 2 therapeutic class "ANTIBACTERIALS FOR SYSTEMIC USE". If a participant took multiple antibiotics on a single day, that day is counted for only once. Protocol defined prophylactic antibiotics for viral, fungal or protozoal infections (e.g. trimethoprim/sulfamethoxazole twice a week for pneumocystis) which are not treated by immunoglobulin, were excluded from this analysis.
Measured: From first dose of study drug up to end of study (up to approximately 1.5 years)
Number of Participants Hospitalized Due to Illness or Infection
Number of participants with hospitalization are standardized to per year (365.25 days). A hospitalization is counted for a specific epoch only if that hospitalization started during that epoch.
Measured: From first dose of study drug up to end of study (up to approximately 1.5 years)
Length of Hospital Stay
Length of hospital stay per stay is standardized to per year (365.25 days). A hospitalization is counted for a specific epoch only if that hospitalization started during that epoch.
Measured: From first dose of study drug up to end of study (up to approximately 1.5 years)
Number of Acute Physician Visits Due to Illness/Infection
Number of acute physician visits is standardized to per year (365.25 days).
Measured: From first dose of study drug up to end of study (up to approximately 1.5 years)
Health-related Quality of Life (HRQoL): Pediatric Quality of Life Inventory (PedsQL) Total Scale Score
Peds-QL=generic HR QoL instrument designed specifically for pediatrics has domains as:general health/activities,feelings/emotional,social functioning,school functioning.In this study,2-7 years (parent as observer),8-13 years (participant as observer) for Peds-QL health questionnaire was analyzed.Higher scores=better QOL for all domains.This modular instrument used 5-point scale:0(never) to 4(almost always).Items are reversed scored;linearly transformed to 0-100 scale as follows:0=100,1=75,2=50,3=25,4=0.4 dimensions(physical, emotional, social, \& school functioning) are scored.PEDS-QL Total Scale Score has 0-100 scale,higher scores=better HRQoL.
Measured: Baseline up to end of study (approximately 1.5 years)
EuroQoL (Quality of Life)-5 Dimensions 3 Levels (EQ-5D-3L) Total Scale Score
EQ-5D-3L health questionnaire=participant answered questionnaire scoring 5 dimensions -mobility,self-care,usual activities, pain/discomfort and anxiety/depression. n this study, 2-11 years (parent as observer),12 years and older (participant as observer) for EQ-5D-3L health questionnaire was analyzed.Health state index score range from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome.EQ visual analogue scale range from 0 to 100, where higher scores indicate better health status.Data is reported as per age groups (2-11 years and >=12 years).
Measured: Baseline up to end of the study (approximately 1.5 years)
Health-related Quality of Life (HRQoL): Short Form-36 Health Survey (SF-36) Score
SF-36=generic quality-of-life instrument that has been widely used to assess HRQL of participants.In this study, 14 years and older (participant as observer) for SF-36 health questionnaire was analyzed. Generic instruments are used in general populations to assess a wide range of domains applicable to a variety of health states, conditions, and diseases.SF-36=36 items aggregated into 8 multi-item scales (physical functioning, role - physical, bodily pain, general health, vitality, social functioning, role - emotional, and mental health), with scores ranging from 0 to 100.Higher scores=better HRQL. As pre-specified in protocol data is reported for participants with age group of 14 years or older.
Measured: Baseline up to end of the study (approximately 1.5 years)
Health Related Quality of Life: Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) Score
TSQM=is a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. In this study, 2-12 years (parent as observer), 13 years and older (participant as observer) for TSQM health questionnaire will be analyzed. TSQM-9 is a 9-item, validated, self-administered instrument used to assess participant's satisfaction with medication. The three domains assessed are effectiveness, convenience, and global satisfaction. The score of each of the 3 domains is based on an algorithm to create a score of 0 to 100. Higher score indicated greater satisfaction in that domain. As pre-specified in protocol, data is reported as per age group (2-12 years and >=13 years).
Measured: Baseline up to end of the study (approximately 1.5 years)
Health Related Quality of Life: Treatment Satisfaction Questionnaire for Life Quality Index (LQI) Score
LQI=self-administered questionnaire developed specifically for participants/legal guardians involved in IGIV treatments.2-13 years (parent as observer),14 years and older (participant as observer) for LQI health questionnaire was analyzed.LQI=15-items, divided into 4 domains: treatment interferences(TI)[6 items],therapy-related problems(TRP)[4 items],therapy setting(TS)[3 items];treatment costs(TC)[2 items].Items are rated on a 7-point Likert-type scale ranging from 1:"Extremely bad" to 7:"Extremely good".Total scores=0 to 100,higher scores=highest possible satisfaction with factors such as independence,therapy convenience,social/school/work activities;health and travel costs.As pre-specified in protocol, data is reported as per age (2-13 years and >=14 years).All-Treated Set included all enrolled participants of age group '2-13 years' and '>=14 years' who received at least 1 dose of study drug (IGIV or IGSC).'n'=Number analysed are participants with data available for analysis.
Measured: Baseline up to end of the study (approximately 1.5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2020
- Study start11 Aug 2020
- Primary completion22 Dec 2021
- Study completion22 Dec 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.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baxalta now part of Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Shire
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04346108
- Sponsor's protocol ID
- TAK-664-3001
- Other IDs
- JapicCTI-205162
- Status last verified
- Sep 2023
- First submitted
- 10 Apr 2020
- Last updated
- 22 Mar 2024
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Open-label, Non-controlled, Multi-dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability, and Efficacy of Immune Globulin Subcutaneous (Human), 20% Solution (IGSC, 20%) in Japanese Subjects With Primary Immunodeficiency Diseases (PID)
- ClinicalTrials.gov ID
- NCT04346108
- Acronym / sponsor ID
- TAK-664-3001
- Conditions
- Primary Immunodeficiency Diseases (PID)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Baxalta now part of ShireIndustry (pharma, biotech, devices)
- Study start
- 11 Aug 2020 (actual)
- Primary completion
- 22 Dec 2021 (actual)
- Study completion
- 22 Dec 2021 (actual)
- First posted
- 15 Apr 2020 (actual)
- Results
- Posted 22 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this study, Japanese participants with primary immunodeficiency diseases were treated with Immune Globulin Subcutaneous (Human), 20% solution, (IGSC, 20%). This study will be in 3 parts:
Part 1: Infusions with Immunoglobulin Intravenous (IGIV) every 3 or 4 weeks for 13 weeks.
Part 2: Participants will switch to weekly subcutaneous infusions with IGSC, 20% for 24 weeks.
Part 3: A subset will receive biweekly subcutaneous infusions with IGSC, 20% for 12 weeks.
The main aim of the study is to assess base levels of Immunoglobulin globulin G (IgG) levels in the blood of the participants after weekly and biweekly treatment with IGSC, 20% (in Parts 2 and 3 of the study). Their PID will be treated by their doctor according to their doctor's usual clinical practice.
Detailed description
This study consists of 3 treatment parts (Epoch 1, 2, 3). The total evaluation period of the study will be 57 weeks in which screening period is for 2-8 weeks and Epoch 1 is from Week 8 to Week 21, Epoch 2 is from Week 21 to Week 45, Epoch 3 is from Week 45 to Week 57.
Each participant will receive IGIV treatment in Epoch 1 for a total of 13 weeks, then switch to weekly subcutaneous (SC) treatment with IGSC, 20% in Epoch 2 for a total of 24 weeks and will continue into Epoch 3 for a total of 12 weeks of biweekly SC treatment with IGSC, 20%. Drug dose in Epoch 2 and Epoch 3 will be adjusted so that it will be an equivalent weekly dose of the dose administered in Epoch 1 and twice the dose administrated in Epoch 2 respectively. Epoch 2 will contain two periods, period 1: dose adjustment period (first 12 weeks) and period 2: evaluation period (second 12 weeks).
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: IGIV 200-600 mg/kg | Experimental | Biological: Immune Globulin Intravenous (IGIV)Participants received 200 to 600 mg/kg of Immunoglobulin Intravenous (IGIV) infusion for every 3 or 4 weeks for up to 13 weeks. |
| Epoch 2: IGSC (20%) 50-200 mg/kg | Experimental | Biological: Immune Globulin Subcutaneous, 20% Solution (IGSC, 20%)Participants who entered to Epoch 2 from Epoch 1 received 50-200 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion once a week up to approximately 24 weeks after Epoch 1. |
| Epoch 3: IGSC (20%) 100-400 mg/kg | Experimental | Biological: Immune Globulin Subcutaneous, 20% Solution (IGSC, 20%)Participants who entered to Epoch 3 from Epoch 1 received 100-400 mg/kg of Immune Globulin Subcutaneous (Human) 20% infusion biweekly up to approximately 12 weeks after Epoch 2. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Be of Japanese descent, defined as born in Japan and having Japanese parents and Japanese maternal and paternal grandparents.
- Participants must have a documented diagnosis of a form of primary humoral immunodeficiency involving antibody formation and requiring gammaglobulin replacement. The diagnosis must be confirmed by the medical director prior to treatment with IGIV.
- Participant is 2 years or older at the time of screening.
- Written informed consent is obtained from either the participants or the participants legally authorized representative prior to any study-related procedures and study product administration.
- Participant has been receiving a consistent dose of IGIV over a period of at least 3 months prior to screening equivalent to approximately 200-600 mg/kg-body weight (BW) per 3- 4 week period, as according to the product package insert
Key exclusion criteria (23 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 presence of renal function impairment defined by estimated glomerular filtration rate (eGFR) is <60 milliliter per minute/ 1.73 square meter (mL/min/1.73m^2).
- Participant has been diagnosed with or has a malignancy (other than adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix), unless the disease-free period prior to screening exceeds 5 years.
- Participant is receiving anti-coagulation therapy or has a history of thrombotic episodes (including deep vein thrombosis, myocardial infarction, cerebrovascular accident, pulmonary embolism) within 12 months prior to screening or a history of thrombophilia.
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 |
|---|---|---|
| Immune Globulin Intravenous (IGIV)Also: Immune Globulin Infusion (Human)Participants will receive IGIV infusion. | Biological | Epoch 1: IGIV 200-600 mg/kg |
| Immune Globulin Subcutaneous, 20% Solution (IGSC, 20%)Also: Immune Globulin Infusion (Human)Participants will receive IGSC, 20% SC infusion. | Biological | Epoch 2: IGSC (20%) 50-200 mg/kg, Epoch 3: IGSC (20%) 100-400 mg/kg |
Primary outcome
Epoch 2: Total Serum Trough Levels of Immune Globulin G (IgG) Antibodies During Period 2
Time frame: Epoch 2 (period 2): Up to 24 weeks
Total serum trough levels of IgG antibodies measured during period 2 of Epoch 2 were assessed.
Epoch 3: Total Serum Trough Levels of IgG Antibodies
Time frame: Epoch 3: Up to Week 12
Total serum trough levels of IgG antibodies measured during Epoch 3 were assessed.
28 secondary outcomes
Epoch 1: Total Serum Trough Levels of IgG Antibodies
Time frame: Epoch 1: Up to Week 13
Epoch 2: Area Under the Curve From Time 0 to Last Interval (AUC0-last) for Total Serum Levels of IgG
Time frame: Epoch 2: Week 21
Epoch 2: AUC0-last for Total Serum Levels of IgG Subclasses
Time frame: Epoch 2: Week 21
Epoch 2: Apparent Clearance (CL/F) for Total Serum Levels of IgG
Time frame: Epoch 2: Week 21
Epoch 2: CL/F for Total Serum Levels of IgG Subclasses
Time frame: Epoch 2: Week 21
Epoch 2: Maximum Concentration (Cmax) for Total Serum Levels of IgG
Time frame: Epoch 2: Week 21
Epoch 2: Cmax for Total Serum Levels of IgG Subclasses
Time frame: Epoch 2: Week 21
Epoch 2: Minimum Concentration (Cmin) for Total Serum Levels of IgG
Time frame: Epoch 2: Week 21
Epoch 2: Cmin for Total Serum Levels of IgG Subclasses
Time frame: Epoch 2: Week 21
Epoch 2: Time to Maximum Concentration (Tmax) for Total Serum Levels of IgG
Time frame: Epoch 2: Week 21
Epoch 2: Tmax for Total Serum Levels of IgG Subclasses
Time frame: Epoch 2: Week 21
Trough Levels of Specific Antibodies to Clinically Relevant Pathogens: Clostridium Tetani Toxoid and Hepatitis B Virus (HBV)
Time frame: Epoch 1 (Week 1); Epoch 2 (Week 1, 24); Epoch 3 (Week 1, 13)
Trough Levels of Specific Antibodies to Clinically Relevant Pathogen: Haemophilus Influenzae (HIB)
Time frame: Epoch 1 (Week 1); Epoch 2 (Week 1, 24); Epoch 3 (Week 1, 13)
Health Related Quality of Life: Treatment Preference
Time frame: Up to approximately 1.5 years
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: From first dose of study drug up to end of study (up to approximately 1.5 years)
Number of Participants With Tolerability Events Related to the Infusion of Study Drug
Time frame: From first dose of study drug up to end of study (up to approximately 1.5 years)
Annual Rate of Validated Acute Serious Bacterial Infections (ASBI)
Time frame: From first dose of study drug up to end of study (up to approximately 1.5 years)
Annual Rate of All Infections Per Year
Time frame: From first dose of study drug up to end of study (up to approximately 1.5 years)
Number of Days Participants Not Able to Attend School or Work to Perform Normal Daily Activities Due to Illness/Infection
Time frame: From first dose of study drug up to end of study (up to approximately 1.5 years)
Number of Days Participants Were on Antibiotics
Time frame: From first dose of study drug up to end of study (up to approximately 1.5 years)
Number of Participants Hospitalized Due to Illness or Infection
Time frame: From first dose of study drug up to end of study (up to approximately 1.5 years)
Length of Hospital Stay
Time frame: From first dose of study drug up to end of study (up to approximately 1.5 years)
Number of Acute Physician Visits Due to Illness/Infection
Time frame: From first dose of study drug up to end of study (up to approximately 1.5 years)
Health-related Quality of Life (HRQoL): Pediatric Quality of Life Inventory (PedsQL) Total Scale Score
Time frame: Baseline up to end of study (approximately 1.5 years)
EuroQoL (Quality of Life)-5 Dimensions 3 Levels (EQ-5D-3L) Total Scale Score
Time frame: Baseline up to end of the study (approximately 1.5 years)
Health-related Quality of Life (HRQoL): Short Form-36 Health Survey (SF-36) Score
Time frame: Baseline up to end of the study (approximately 1.5 years)
Health Related Quality of Life: Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) Score
Time frame: Baseline up to end of the study (approximately 1.5 years)
Health Related Quality of Life: Treatment Satisfaction Questionnaire for Life Quality Index (LQI) Score
Time frame: Baseline up to end of the study (approximately 1.5 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Immune Globulin Intravenous (IGIV) and Immune Globulin Subcutaneous, 20% Solution (IGSC, 20%) in people with Primary Immunodeficiency Diseases (PID), run by Baxalta now part of Shire at 8 sites in Japan.
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 8 inclusion and 23 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 22 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Japan. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 22 Mar 2024). 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?
Epoch 2: Total Serum Trough Levels of Immune Globulin G (IgG) Antibodies During Period 2 (time frame: Epoch 2 (period 2): Up to 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Mar 2024.