Clinical trial NCT04346108: A Study of Immune Globulin Subcutaneous (Human), 20% Solution (IGSC, 20%) in Japanese Participants With Primary Immunodeficiency Diseases (PID)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Immunodeficiency Diseases (PID)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2020-04-15
Enrollment: 17
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 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).

Eligibility 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 \>= 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) \> 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.
* 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.

Primary outcomes:
measure: Epoch 2: Total Serum Trough Levels of Immune Globulin G (IgG) Antibodies During Period 2
timeFrame: Epoch 2 (period 2): Up to 24 weeks
measure: Epoch 3: Total Serum Trough Levels of IgG Antibodies
timeFrame: Epoch 3: Up to Week 12
Secondary outcomes:
measure: Epoch 1: Total Serum Trough Levels of IgG Antibodies
timeFrame: Epoch 1: Up to Week 13
measure: Epoch 2: Area Under the Curve From Time 0 to Last Interval (AUC0-last) for Total Serum Levels of IgG
timeFrame: Epoch 2: Week 21
measure: Epoch 2: AUC0-last for Total Serum Levels of IgG Subclasses
timeFrame: Epoch 2: Week 21
measure: Epoch 2: Apparent Clearance (CL/F) for Total Serum Levels of IgG
timeFrame: Epoch 2: Week 21
measure: Epoch 2: CL/F for Total Serum Levels of IgG Subclasses
timeFrame: Epoch 2: Week 21
measure: Epoch 2: Maximum Concentration (Cmax) for Total Serum Levels of IgG
timeFrame: Epoch 2: Week 21
measure: Epoch 2: Cmax for Total Serum Levels of IgG Subclasses
timeFrame: Epoch 2: Week 21
measure: Epoch 2: Minimum Concentration (Cmin) for Total Serum Levels of IgG
timeFrame: Epoch 2: Week 21
measure: Epoch 2: Cmin for Total Serum Levels of IgG Subclasses
timeFrame: Epoch 2: Week 21
measure: Epoch 2: Time to Maximum Concentration (Tmax) for Total Serum Levels of IgG
timeFrame: Epoch 2: Week 21
measure: Epoch 2: Tmax for Total Serum Levels of IgG Subclasses
timeFrame: Epoch 2: Week 21
measure: Trough Levels of Specific Antibodies to Clinically Relevant Pathogens: Clostridium Tetani Toxoid and Hepatitis B Virus (HBV)
timeFrame: Epoch 1 (Week 1); Epoch 2 (Week 1, 24); Epoch 3 (Week 1, 13)
measure: Trough Levels of Specific Antibodies to Clinically Relevant Pathogen: Haemophilus Influenzae (HIB)
timeFrame: Epoch 1 (Week 1); Epoch 2 (Week 1, 24); Epoch 3 (Week 1, 13)
measure: Health Related Quality of Life: Treatment Preference
timeFrame: Up to approximately 1.5 years
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug up to end of study (up to approximately 1.5 years)
measure: Number of Participants With Tolerability Events Related to the Infusion of Study Drug
timeFrame: From first dose of study drug up to end of study (up to approximately 1.5 years)
measure: Annual Rate of Validated Acute Serious Bacterial Infections (ASBI)
timeFrame: From first dose of study drug up to end of study (up to approximately 1.5 years)
measure: Annual Rate of All Infections Per Year
timeFrame: From first dose of study drug up to end of study (up to approximately 1.5 years)
measure: Number of Days Participants Not Able to Attend School or Work to Perform Normal Daily Activities Due to Illness/Infection
timeFrame: From first dose of study drug up to end of study (up to approximately 1.5 years)
measure: Number of Days Participants Were on Antibiotics
timeFrame: From first dose of study drug up to end of study (up to approximately 1.5 years)
measure: Number of Participants Hospitalized Due to Illness or Infection
timeFrame: From first dose of study drug up to end of study (up to approximately 1.5 years)
measure: Length of Hospital Stay
timeFrame: From first dose of study drug up to end of study (up to approximately 1.5 years)
measure: Number of Acute Physician Visits Due to Illness/Infection
timeFrame: From first dose of study drug up to end of study (up to approximately 1.5 years)
measure: Health-related Quality of Life (HRQoL): Pediatric Quality of Life Inventory (PedsQL) Total Scale Score
timeFrame: Baseline up to end of study (approximately 1.5 years)
measure: EuroQoL (Quality of Life)-5 Dimensions 3 Levels (EQ-5D-3L) Total Scale Score
timeFrame: Baseline up to end of the study (approximately 1.5 years)
measure: Health-related Quality of Life (HRQoL): Short Form-36 Health Survey (SF-36) Score
timeFrame: Baseline up to end of the study (approximately 1.5 years)
measure: Health Related Quality of Life: Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) Score
timeFrame: Baseline up to end of the study (approximately 1.5 years)
measure: Health Related Quality of Life: Treatment Satisfaction Questionnaire for Life Quality Index (LQI) Score
timeFrame: Baseline up to end of the study (approximately 1.5 years)
Other outcomes:
Locations:
city: Nagoya-shi
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Fukuoka-shi
country: Japan
facility: Kyushu University Hospital
state: Fukuoka
city: Kurume-shi
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Gifu-shi
country: Japan
facility: Gifu University Hospital
state: Gifu
city: Hiroshima-shi
country: Japan
facility: Hiroshima University Hospital
state: Hiroshima
city: Kanazawa-shi
country: Japan
facility: Kanazawa University Hospital
state: Ishikawa
city: Tokorozawa-shi
country: Japan
facility: National Defense Medical College Hospital
state: Saitama
city: Bunkyo-ku
country: Japan
facility: Tokyo Medical Dental University Hospital
state: Tokyo
Study officials:
affiliation: Shire
name: Study Director
role: STUDY_DIRECTOR
References: