We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Immune Globulin Subcutaneous (Human), 20% Solution (IGSC, 20%) in Japanese Participants With Primary Immunodeficiency Diseases (PID)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04346108
Recruitment Status : Completed
First Posted : April 15, 2020
Last Update Posted : February 24, 2022
Sponsor:
Information provided by (Responsible Party):
Takeda ( Baxalta now part of Shire )

Brief 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 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.


Condition or disease Intervention/treatment Phase
Primary Immunodeficiency Diseases (PID) Biological: Immune Globulin Intravenous (IGIV) Biological: Immune Globulin Subcutaneous, 20% Solution (IGSC, 20%) Phase 3

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).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : August 11, 2020
Actual Primary Completion Date : December 22, 2021
Actual Study Completion Date : December 22, 2021


Arm Intervention/treatment
Experimental: Epoch 1: Immune Globulin Intravenous (IGIV)
Participants will receive approximately 200 to 600 milligrams per kilogram (mg/kg) of Immunoglobulin Globulin Intravenous (IGIV) infusion for every 3 or 4 weeks for a total of 13 weeks.
Biological: Immune Globulin Intravenous (IGIV)
Participants will receive IGIV infusion.
Other Name: Immune Globulin Infusion (Human)

Experimental: Epoch 2: Immune Globulin Subcutaneous 20% Solution (IGSC)
Participants will receive approximately 50 to 200 mg/kg of IGSC infusion, 20 percent (%) once a week for a total of 24 weeks.
Biological: Immune Globulin Subcutaneous, 20% Solution (IGSC, 20%)
Participants will receive IGSC, 20% SC infusion.
Other Name: Immune Globulin Infusion (Human)

Experimental: Epoch 3: Immune Globulin Subcutaneous 20% Solution (IGSC)
Participants will receive approximately 100 to 400 mg/kg of IGSC infusion, 20% once every two weeks in a sub-set of 7 participants for a total of 12 weeks.
Biological: Immune Globulin Subcutaneous, 20% Solution (IGSC, 20%)
Participants will receive IGSC, 20% SC infusion.
Other Name: Immune Globulin Infusion (Human)




Primary Outcome Measures :
  1. Epoch 2: Total Serum Trough Levels of Immune Globulin G (IgG) Antibodies During Period 2 [ Time Frame: Epoch 2 (period 2): Up to 21 weeks ]
    Total serum trough levels of IgG antibodies measured during period 2 of Epoch 2 will be assessed.

  2. Epoch 3: Total Serum Trough Levels of Immune Globulin G (IgG) Antibodies [ Time Frame: Epoch 3: Up to Week 13 ]
    Total serum trough levels of IgG antibodies measured during Epoch 3 will be assessed.


Secondary Outcome Measures :
  1. Epoch 1: Total Serum Trough Levels of Immune Globulin G (IgG) Antibodies [ Time Frame: Epoch 1: Up to Week 13 ]
    Total serum trough levels of IgG antibodies measured during Epoch 1 will be assessed.

  2. Epoch 2: Area Under the Curve (AUC) for Total Serum Levels of IgG and IgG Subclasses [ Time Frame: Epoch 2: Week 21: Pre-infusion (Day 0), Day 1, 3, 5, and 7 ]
    AUC for total serum levels for IgG and IgG Subclasses will be assessed. All Pharmacokinetic (PK) serial sampling will start at Epoch 2 SC infusion at Week 21.

  3. Epoch 2: Apparent Clearance (CL/F) for Total Serum Levels of IgG and IgG Subclasses [ Time Frame: Epoch 2: Week 21: Pre-infusion (Day 0), Day 1, 3, 5, and 7 ]
    Cl/F for total serum levels of IgG and IgG Subclasses will be assessed. All PK serial sampling will start at Epoch 2 SC infusion at Week 21.

  4. Epoch 2: Maximum Concentration (Cmax) for Total Serum Levels of IgG and IgG Subclasses [ Time Frame: Epoch 2: Week 21: Pre-infusion (Day 0), Day 1, 3, 5, and 7 ]
    Cmax for total serum levels of IgG and IgG Subclasses will be assessed.All PK serial sampling will start at Epoch 2 SC infusion at Week 21.

  5. Epoch 2: Minimum Concentration (Cmin) for Total Serum Levels of IgG and IgG Subclasses [ Time Frame: Epoch 2: Week 21: Pre-infusion (Day 0), Day 1, 3, 5, and 7 ]
    Cmin for total serum levels of IgG and IgG Subclasses will be assessed. All PK serial sampling will start at Epoch 2 SC infusion at Week 21.

  6. Epoch 2: Time to Maximum Concentration (Tmax) for Total Serum Levels of IgG and IgG Subclasses [ Time Frame: Epoch 2: Week 21: Pre-infusion (Day 0), Day 1, 3, 5, and 7 ]
    Tmax for total serum levels of IgG and IgG Subclasses will be assessed. All PK serial sampling will start at Epoch 2 SC infusion at Week 21.

  7. Trough Levels of Specific Antibodies to Clinically Relevant Pathogens [ Time Frame: Epoch 1 (Week 1); Epoch 2 (Week 1); Epoch 3 (Week 1, 13) ]
    Trough levels of specific antibodies to clinically relevant pathogens (Clostridium tetani toxoid, HIB, HBV) will be assessed in Epoch 1, Epoch 2 and Epoch 3.

  8. Number of Participants with Treatment Emergent Adverse Events (TEAEs) [ Time Frame: From start of study up to Week 57 ]
    TEAEs is defined as Adverse events (AEs) with onset after date-time of first dose of IP, 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 will be considered as IGSC, 20%-related AE, and any AE recorded as "unlikely related" or "not related" will be considered as unrelated AE. AEs will includes vital signs, clinical laboratory measurements. Number of participants with TEAEs will be assessed.

  9. Number of Participants with Tolerability Events Related to the Infusion of Investigational Product (IP) [ Time Frame: From start of study up to Week 57 ]
    An infusion is considered tolerable if the infusion rate was not reduced, or the infusion was not interrupted or stopped, due to IP TEAE related to study drug (IGIV or IGSC) infusion. A tolerability event is considered to have occurred if an infusion was tolerable in Epoch 1, Epoch 2 and Epoch 3. Number of participants with tolerability events related to infusion of IP will be assessed.

  10. Annual Rate of Validated Acute Serious Bacterial Infections (ASBI) [ Time Frame: From start of study up to Week 57 ]
    The ASBI rate will be calculated as the mean number of acute serious bacterial infections per participants per year. Annual rate of validated acute serious bacterial infections per subject will be assessed.

  11. Annual Rate of All Infections [ Time Frame: From start of study up to Week 57 ]
    Annual rate is the number of participants reporting any infection per year.

  12. Number of Days Participants not Able to Attend School or Work to Perform Normal Daily Activities due to Illness/Infection [ Time Frame: From start of study up to Week 57 ]
    Number of days not able to attend school or work to perform normal daily activities due to illness/infection will be assessed.

  13. Number of Days Participants on Antibiotics [ Time Frame: From start of study up to Week 57 ]
    Number of days participants on antibiotics will be assessed.

  14. Number of Participants Hospitalized due to Illness or Infection [ Time Frame: From start of study up to Week 57 ]
    Number of participants will report hospitalizations due to illness or infection will be assessed.

  15. Length of Hospital Stay [ Time Frame: From start of study up to Week 57 ]
    Number of days participants stay in hospital.

  16. Number of Participants will Report Acute Physician Visits due to Illness/Infection [ Time Frame: From start of study up to Week 57 ]
    Number of participants will report acute (urgent or unscheduled) physician visits due to illness or infection will be reported.

  17. Health-related Quality of Life (HRQoL): Pediatric Quality of Life Inventory (PedsQL) [ Time Frame: Epoch 1 (Week 1); Epoch 2 (Week 1); Epoch 3 (Week 1, 13) ]
    The Peds-QL is a generic Health-Related Quality of Life (HR QoL) instrument designed specifically for a pediatric population. It captures the following domains: 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 will be analyzed. Higher scores indicate better quality of life (QOL) for all domains of the Peds-QL. This modular instrument uses a 5-point scale: from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Four dimensions (physical, emotional, social, & school functioning) are scored.

  18. EuroQoL (Quality of Life)-5 Dimensions 3 Levels (EQ-5D-3L) [ Time Frame: Epoch 1 (Week 1); Epoch 2 (Week 1); Epoch 3 (Week 1, 13) ]
    EQ-5D-3L health questionnaire is a participant answered questionnaire scoring 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression. In this study, 2-11 years (parent as observer),12 years and older (participant as observer) for EQ-5D-3L health questionnaire will be analyzed. The EQ-5D-3L total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome.

  19. Health-related Quality of Life (HRQoL): Short Form-36 Health Survey (SF-36) [ Time Frame: Epoch 1 (Week 1); Epoch 2 (Week 1); Epoch 3 (Week 1, 13) ]
    The SF-36 is a generic quality-of-life instrument that has been widely used to assess health-related quality of life (HRQL) of participants. In this study, 14 years and older (participant as observer) for SF-36 health questionnaire will be 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. The SF-36 consists of 36 items that are 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 indicate better HRQL.

  20. Health Related Quality of Life: Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) [ Time Frame: Epoch 1 (Week 1); Epoch 2 (Week 1); Epoch 3 (Week 1, 13) ]
    Treatment Satisfaction Questionnaire for Medication (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.

  21. Health Related Quality of Life: Treatment Satisfaction Questionnaire for Life Quality Index (LQI) [ Time Frame: Epoch 1 (Week 1); Epoch 2 (Week 1); Epoch 3 (Week 1, 13) ]
    The LQI is a self-administered questionnaire developed specifically for participants/legal guardians involved in IGIV treatments. In this study, 2-13 years (parent as observer), 14 years and older (participant as observer) for LQI health questionnaire will be analyzed. LQI consists of 15-items, divided into four domains: treatment interferences (6 items), therapy-related problems (4 items), therapy setting (3 items), and treatment costs (2 items). Items are rated on a 7-point Likert-type scale ranging from 1: "Extremely bad" to 7: "Extremely good". Total scores range from 15 to 105, with higher scores indicating the highest possible satisfaction with factors such as independence, therapy convenience, social/school/work activities, and health and travel costs.

  22. Health Related Quality of Life: Treatment Preference [ Time Frame: Up to Week 57 ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 greater than or equal to (>=) 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.

Exclusion Criteria:

  • 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) greater than (>) 2.5 times the upper limit of normal (ULN) for the testing laboratory
    • Persistent severe neutropenia (defined as an absolute neutrophil count [ANC] lesser than or equal to (<=) 500/milli cubic meter [mm^3]).
  • Participant has presence of renal function impairment defined by estimated glomerular filtration rate (eGFR) is less than (<) 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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04346108


Locations
Layout table for location information
Japan
Nagoya University Hospital
Nagoya-shi, Aichi, Japan, 466-8560
Kyushu University Hospital
Fukuoka-shi, Fukuoka, Japan, 812-8582
Kurume University Hospital
Kurume-shi, Fukuoka, Japan, 830-0011
Gifu University Hospital
Gifu-shi, Gifu, Japan, 501-1194
Hiroshima University Hospital
Hiroshima-shi, Hiroshima, Japan, 734-8551
Kanazawa University Hospital
Kanazawa-shi, Ishikawa, Japan, 920-8641
National Defense Medical College Hospital
Tokorozawa-shi, Saitama, Japan, 359-8513
Tokyo Medical Dental University Hospital
Bunkyo-ku, Tokyo, Japan, 113-8519
Sponsors and Collaborators
Baxalta now part of Shire
Investigators
Layout table for investigator information
Study Director: Study Director Shire
Layout table for additonal information
Responsible Party: Baxalta now part of Shire
ClinicalTrials.gov Identifier: NCT04346108    
Other Study ID Numbers: TAK-664-3001
JapicCTI-205162 ( Registry Identifier: JapicCTI )
First Posted: April 15, 2020    Key Record Dates
Last Update Posted: February 24, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
URL: https://vivli.org/ourmember/takeda/

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Primary Immunodeficiency Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Genetic Diseases, Inborn
Immunoglobulins
Antibodies
gamma-Globulins
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunoglobulin G
Immunologic Factors
Physiological Effects of Drugs