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Immune Globulin, 10% TVR

Phase 3

Alzheimer´s Disease | Monoclonal antibody | Neurology |Takeda Pharmaceutical Company Limited|Last Updated: Mar 22, 2024

Target and mechanism

ModalityMonoclonal antibody

Also known as Immune Globulin Intravenous (Human), 10%, Immune Globulin, 10%, Immune Globulin Intravenous (Human), 10% Solution, Immune Globulin, 10% Triple Virally Reduced, Immune Globulin Subcutaneous (Human), 20%, Immune Globulin, 20%, Immune Globulin Intravenous (IGIV), Immune Globulin

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials1
Total Enrollment390

FDA Designations

No designations recorded

Clinical trial landscape

Immune Globulin, 10% TVR · 9 trials · 7 indications

Phase 3 4Phase 2 5
NCT04346108A Study of Immune Globulin Subcutaneous (Human), 20% Solution (IGSC, 20%) in Japanese Participants With Primary Immunodeficiency Diseases (PID)Primary Immunodeficiency Diseases (PID)
COMPLETED17 Analytics
NCT00818662A Phase 3 Study Evaluating Safety and Effectiveness of Immune Globulin Intravenous (IGIV 10%) for the Treatment of Mild-to-Moderate Alzheimer´s DiseaseAlzheimer´s Disease
COMPLETED390 Analytics
NCT00666263Study of the Effectiveness of Intravenous Immune Globulin (10%) for the Treatment of Multifocal Motor NeuropathyMultifocal Motor Neuropathy
COMPLETED50 Analytics
NCT00157079Safety and Efficacy Study of a 10% Intravenous Immune Globulin Solution in Subjects With Primary Immunodeficiency DisordersPrimary Immunodeficiency Diseases (PID)
COMPLETED61 Analytics
PHASE3COMPLETED
A Study of Immune Globulin Subcutaneous (Human), 20% Solution (IGSC, 20%) in Japanese Participants With Primary Immunodeficiency Diseases (PID)
Primary Immunodeficiency Diseases (PID)Unlock trial analytics
PHASE3COMPLETED
A Phase 3 Study Evaluating Safety and Effectiveness of Immune Globulin Intravenous (IGIV 10%) for the Treatment of Mild-to-Moderate Alzheimer´s Disease
Alzheimer´s DiseaseUnlock trial analytics
PHASE3COMPLETED
Study of the Effectiveness of Intravenous Immune Globulin (10%) for the Treatment of Multifocal Motor Neuropathy
Multifocal Motor NeuropathyUnlock trial analytics
PHASE3COMPLETED
Safety and Efficacy Study of a 10% Intravenous Immune Globulin Solution in Subjects With Primary Immunodeficiency Disorders
Primary Immunodeficiency Diseases (PID)Unlock trial analytics

Study Endpoints

Primary Endpoints

Epoch 2: Total Serum Trough Levels of Immune Globulin G (IgG) Antibodies During Period 2
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
Epoch 3: Up to Week 12

Total serum trough levels of IgG antibodies measured during Epoch 3 were assessed.

Change From Baseline at 18 Months in the Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog)
Baseline & 18 months

The ADAS-Cog is a validated psychometric instrument that evaluates memory (word recall, word recognition), attention, reasoning (following commands), language (naming, comprehension), orientation, ideational praxis (placing letter in envelope) and constructional praxis (copying geometric designs). This test was administered by experienced raters certified by Alzheimer's Disease Cooperative Study (ADCS) at each site. Scores on the ADAS-Cog range from 0-70 with higher scores indicating greater impairment; hence increases from baseline reflect potential cognitive deterioration.

Change From Baseline at 18 Months in Alzheimer´s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)
Baseline & 18 Months

The ADCS-ADL scale is a validated tool to assess instrumental and basic activities of daily living based on a 23 item structured interview of the caregiver or qualified study partner. Scores on the ADCS-ADL range from 0-78 with lower scores indicating greater impairment; hence decreases from baseline reflect potential functional deterioration.

Grip Strength in the More Affected Hand
Week 0, then at Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit

The grip strength was measured using a DynEx digital dynamometer. The result of grip strength was recorded to a resolution of 0.1 kg. Each grip strength test consisted of 3 maximal repeated contractions (trials). Each participant will perform 2 sessions of grip strength testing. After a 10-minute break, the testing session will be repeated for a total of 6 grip repetitions per hand.

Mean Relative Change in Grip Strength in the More Affected Hand
Baseline and last infusion cycle during the two study cross-over periods, approximately weeks 13 and 24; and weeks 37 and 48 (i.e. baseline and end of Study Parts 2 and 4)

Relative Change is defined as 100 \* (End of the Cross-Over Period - baseline of Cross-Over Period) divided by baseline of Cross-Over Period. The grip strength was measured using a DynEx digital dynamometer. The result of grip strength was recorded to a resolution of 0.1 kg. For statistical analysis, the mean of (usually three) trials for cross-over sessions 1 and 2 was computed and the mean of the sessions was used in the analysis as the result of the grip strength measurement. Only if no grip strength testing could be performed the results were considered as missing.

Co-Primary Endpoint: Guy's Neurologic Disability Scale (GNDS) for Upper Limbs
Week 0, then at Last infusion cycle for each study part (Day 8 of last treatment cycle for 2-week interval or Day 15 of last treatment cycle for 3 or 4 -week interval), then at the end of study visit

GNDS (based on Sharrack and Hughes, 1999) for the upper limbs were integers 0 to 5, with 0 indicating no impairment.

Co-Primary Endpoint: Proportion of Participants With Deterioration in Guy's Neurological Disability Score (GNDS)
Baseline and last infusion cycle during the two study cross-over periods, approximately weeks 13 and 24; and weeks 37 and 48 (i.e. baseline and end of Study Parts 2 and 4)

GNDS (based on Sharrack and Hughes, 1999) for the upper limbs were integers 0 to 5, with 0 indicating no impairment.

Rate of Temporally Associated Adverse Events (AEs) Per Infusion
Within 72 hours of completion of an infusion during the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)

The total number of all AEs which begin during or within 72 hours of completion of an infusion, irrespective of being related or not related to the study product (IGIV, 10% or Placebo), divided by the total number of infusions, and multiplied by 100.

The Percentage of Participants for Whom the Infusion Rate of Any Infusion Was Reduced and/or the Infusion Was Interrupted or Stopped for Any Reason
Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)
The Percentage of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped for Any Reason
Throughout the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)
The Percentage of Participants Reporting One or More Moderate or Severe AEs That Began During Infusion or Within 72 Hours of Completion of an Infusion
Within 72 hours of completion of an infusion during the two study cross-over periods, approximately weeks 13-24 and weeks 37-48 (i.e. Study Parts 2 and 4)
Mean number of acute serious bacterial infections per participant per year
Throughout the study period of 18 months
Rate of Acute Serious Bacterial Infections Per Year (ASBI)
1 year

Annual rate of validated acute serious bacterial infections was calculated using a Poisson model to account for the different lengths of observation per participant. The observation period for each participant starts with the day of the first subcutaneous (SC) infusion in Study Epoch 2 and ends with the day of the End of Study visit.

Acute serious bacterial infection rate defined as the mean number of acute serious bacterial infections per subject per year in the intent-to-treat population
1 year

Acute serious bacterial infections will include bacteremia / sepsis, bacterial meningitis, osteomyelitis / septic arthritis, bacterial pneumonia, and visceral abscess, diagnosed according to the Diagnostic Criteria for Serious Acute Bacterial Infections

Ratio of Area Under the Concentration Curve (AUC 0-τ)/Week Following IV Administration to SC Administration of IGIV, 10% at an Adjusted/Individual Adapted Dose (Part 3b), Expressed as a Percentage
Week 12 (IV) and week 32 or 33 (SC)

Expressed as (AUC\_SC/AUC\_IV) \* 100

Bioavailability (Trough Levels) of IgG After Administration of IGIV, 10%, in Participants Aged 2 to <12 Years.
Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visits 1, and 5 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; and at the end-of-study evaluation

Administration of IGIV, 10%: - Part 1 = IV administration (IV) - Parts 2, 3a, 3b = SC administration (SC)

Percentage of Participants in Full Safety Data Set (FSDS) Who Had Any Infusion for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Throughout study (1 year and 9 months)

Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of participants for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs

Percentage of Participants Naïve to SC Administration of Immunoglobulins (SNSC) Who Had Any Infusion for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped.
Throughout study (1 year and 9 months)

Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of participants for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs

Percentage of Participants With Prior Experience With Subcutaneous Administration of Immunoglobulins (SESC) Who Had Any Infusion for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Throughout study (1 year and 9 months)

Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of participants for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs

Percentage of Infusions in FSDS for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Throughout study (1 year and 9 months)

Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of infusions for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs

Percentage of Infusions in SNSC for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Throughout study (1 year and 9 months)

Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of infusions for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs

Percentage of Infusions in SESC for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped
Throughout study (1 year and 9 months)

Ability to tolerate IGIV, 10% administered IV or SC. Measured as the percentage of infusions for which the infusion rate was reduced at any infusion and/or the infusion was interrupted or stopped for (i) any reason and (ii) for tolerability concerns or AEs

Subjects Who Qualify As Treatment Responders
Baseline thru Day 15 post treatment

Subjects who i) had at least one platelet count of ≥50 x 109/L prior to Day 15 and ii) did not require a booster dose prior to Day 15, where Day 15 refers to the fifteenth day after initiation of treatment (Day 1). Otherwise, the subject is a non-responder.

Pharmacokinetics: Trough levels of total immunoglobulin G (IgG) after treatment with Immune Globulin Intravenous (Human), 10% Triple Virally Reduced Solution (IGIV, 10% TVR Solution)
21 days after each infusion (i.e., before the next infusion) of the study drug and at the last visit

Secondary Endpoints

Epoch 1: Total Serum Trough Levels of IgG Antibodies
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
Epoch 2: Week 21
Epoch 2: AUC0-last for Total Serum Levels of IgG Subclasses
Epoch 2: Week 21
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Study Design & Arms

AllocationNON_RANDOMIZED
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Epoch 1: IGIV 200-600 mg/kgEXPERIMENTALParticipants 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/kgEXPERIMENTALParticipants 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/kgEXPERIMENTALParticipants 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.
IGIV, 10% 400mg/kgEXPERIMENTALImmune Globulin Intravenous (Human), 10% (IGIV, 10%)
IGIV, 10% 200mg/kgEXPERIMENTALImmune Globulin Intravenous (Human), 10% (IGIV, 10%)
Human Albumin 0.25% Solution - 4 mL/kgPLACEBO_COMPARATOR0.25% human albumin solution infused at 4 mL/kg/2weeks
Human Albumin 0.25% Solution - 2 mL/kgPLACEBO_COMPARATOR0.25% human albumin solution infused at 2 mL/kg/2weeks
IGIV, 10% Then PlaceboEXPERIMENTALSTUDY PART 1: Open-label stabilization on IGIV, 10% (Stabilization Phase 1) all participants. STUDY PART 2: IGIV, 10% (double-blind treatment Cross-Over Period 1). STUDY PART 3: Between the two double-blind treatment cross-over periods, participants received open-label treatment/stabilization with IGIV, 10% (Stabilization Phase 2). STUDY PART 4: Placebo (0.25% human albumin: BUMINATE 25% Albumin (Human)(Baxter Healthcare Corporation) used where licensed; otherwise Human Albumin 200 g/L Baxter Solution for Infusion was used) (double-blind treatment cross-over period 2). STUDY PART 5: Participants received open-label treatment/stabilization with IGIV, 10% (Stabilization Phase 3). Each study part was 12 weeks in length. Participants received IGIV, 10% at the same equivalent dose per week administered prior to the study (0.4 to 2.0 g per kg body weight (BW) per infusion cycle).
Placebo Then IGIV, 10%EXPERIMENTALSTUDY PART 1: Open-label stabilization on IGIV, 10% (Stabilization Phase 1) all participants. STUDY PART 2: Placebo (0.25% human albumin: BUMINATE 25% Albumin (Human) (Baxter Healthcare Corporation) used where licensed; otherwise Human Albumin 200 g/L Baxter Solution for Infusion was used) (double-blind treatment Cross-Over Period 1). STUDY PART 3: Between the two double-blind treatment cross-over periods, participants received open-label treatment/stabilization with IGIV, 10% (Stabilization Phase 2). STUDY PART 4: IGIV, 10% (double-blind treatment cross-over period 2). STUDY PART 5: Participants received open-label treatment/stabilization with IGIV, 10% (Stabilization Phase 3). Each study part was 12 weeks in length. Participants received IGIV, 10% at the same equivalent dose per week administered prior to the study (0.4 to 2.0 g per kg BW per infusion cycle)
Study Epochs 1-4EXPERIMENTALEpoch 1 (13 weeks): Pharmacokinetic (PK) assessment at 2nd to last infusion (in all participants ≥12 years of age). Participants will be treated intravenously once every 3 or 4 weeks at same monthly equivalent dose as prior to the study. Epoch 2 (12-16 weeks): PK assessment (in first 15 participants ≥12 years of age) at 9th infusion to determine adjusted dose for Epoch 3 and individually adapted dose for Epoch 4. Participants will be treated subcutaneously every 7 days at a dose of IGSC, 20% that is 145% of the weekly equivalent of the IV dose in Epoch 1. Epoch 3 (12 weeks): Participants will be treated subcutaneously every 7 days using the adjusted dose determined in Epoch 2. The individually adapted dose for use in Epoch 4 will also be determined. Epoch 4 (40 weeks): Participants will be treated subcutaneously once every week at the individually adapted dose determined in Epoch 3. PK assessment at 17th infusion.
Epoch 1 (intravenous pre-study treatment) + Epoch 2EXPERIMENTALStudy Epoch 1 (13 weeks): treatment with KIOVIG (once every 3 or 4 weeks, dose as during pre-study period) + Study Epoch 2 (same for all subjects, 51 weeks): treatment with IGSC, 20% (every week, dose to be calculated on the basis of weekly equivalents)
Epoch 1 (subcutaneous pre-study treatment) + Epoch 2EXPERIMENTALStudy Epoch 1 (12 weeks): treatment with SUBCUVIA (once every week or once every two weeks, dose as during pre-study period) + Study Epoch 2 (same for all subjects, 51 weeks): treatment with IGSC, 20% (every week, dose to be calculated on the basis of weekly equivalents)

Interventions

NameTypeDescription
Immune Globulin Intravenous (IGIV)BIOLOGICALParticipants will receive IGIV infusion.
Immune Globulin Subcutaneous, 20% Solution (IGSC, 20%)BIOLOGICALParticipants will receive IGSC, 20% SC infusion.
Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 400 mg/kgBIOLOGICAL400 mg/kg bodyweight every 2 weeks for 70 weeks
Immune Globulin Intravenous (Human), 10% (IGIV, 10%) 200 mg/kgBIOLOGICAL200 mg/kg bodyweight every 2 weeks for 70 weeks
Placebo solution: Human Albumin 0.25% - 4 mL/kgBIOLOGICALPlacebo solution: 0.25% human albumin solution infused at 4 mL/kg/2weeks for 70 weeks
Placebo solution: Human Albumin 0.25% - 2 mL/kgBIOLOGICALPlacebo solution: 0.25% human albumin solution infused at 2 mL/kg/2weeks for 70 weeks
Immune Globulin Intravenous (human), 10%BIOLOGICALDose: Previous dose with 3, 4, or 6 cycles depending on previous schedule (patient specific)
0.25% human albumin solution (Placebo)BIOLOGICALCross-over Period 1 (Randomized) / Cross-over Period 2 (opposite of the treatment received in Cross-over Period 1); Dose: Same volume/frequency as Stabilization Phase 1
Immune Globulin Intravenous (Human), 10% SolutionBIOLOGICALIntravenous infusion with IGIV, 10%
Immune Globulin Subcutaneous (Human), 20% SolutionDRUGSubcutaneous infusion with IGSC, 20%
Immune Globulin Subcutaneous (Human), 20%BIOLOGICALSubcutaneous infusion (regulated via a pump), Epoch 2 only (all subjects)
Human Normal Immunoglobulin (Subcutaneous - Intramuscular Immunoglobulin)BIOLOGICALSubcutaneous infusion (regulated via a pump)
Immune Globulin Intravenous (Human), 10% Triple Virally Reduced SolutionDRUG -
Immune Globulin Intravenous (Human), 10% TVR (Triple Virally Reduced) SolutionDRUG -
Gammagard S/D (Solvent/Detergent)DRUG -
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Eligibility Criteria

Age Range2 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites8

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 ...

Countries:JapanUnited StatesCanadaDenmarkAustriaGermanyHungarySwedenUnited KingdomCzechiaPolandFinland
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Frequently asked questions about Immune Globulin, 10% TVR

What is Immune Globulin, 10% used for?

Immune Globulin, 10% is an investigational therapy being studied for the treatment of Multifocal Motor Neuropathy and Primary Immunodeficiency Diseases (PID). It is currently in Phase 3 clinical development for these indications, though no active trials are ongoing as all five studies have been completed.

Who makes Immune Globulin, 10%?

Immune Globulin, 10% is being developed by Takeda Pharmaceutical Company Limited, which trades under the ticker TAK. The company has conducted clinical trials for this product in the United States, Canada, Denmark, and several European countries.

What phase is Immune Globulin, 10% in?

Immune Globulin, 10% is in Phase 3 clinical development. The development program includes completed Phase 2 and Phase 3 trials, with a total of five studies completed and no active trials currently enrolling. It remains an investigational product and is not yet approved.

What clinical trials has Immune Globulin, 10% been in?

Immune Globulin, 10% has been studied in five completed trials. Key studies include NCT00666263, a Phase 3 trial for Multifocal Motor Neuropathy, and NCT00546871, a Phase 2 trial in Primary Immunodeficiency Diseases. Other trials include NCT01218438 and NCT01412385, which evaluated related formulations.

Is Immune Globulin, 10% the same as IGSC, 20%?

No, Immune Globulin, 10% is distinct from IGSC, 20%, which is a separate formulation studied in the Phase 2/3 trial NCT01218438 for Primary Immunodeficiency Diseases. The 10% and 20% products differ in concentration and are evaluated in different clinical trials within the same development program.