Agammaglobulinemia, Antibody Deficiency, Hypogammaglobulinemia, Primary Immunodeficiency
Conditions
Keywords
Primary Immunodeficiency, PID, Agammaglobulinemia, Hypogammaglobulinemia, Antibody deficiency
Brief summary
The purpose of this study is to determine whether Kedrion IVIG 10% (an immunoglobulin solution) is effective in treating Primary Immunodeficiency (PID).
Detailed description
People with primary immunodeficiency diseases (PID) have a defective immune system and experience recurrent protozoal, bacterial, fungal and viral infections. Antibody deficiencies make up the largest group of PIDs. The standard care for patients with PID is replacement immunoglobulin (a class of antibodies) solution. Prophylactic treatment with intravenous immunoglobulin (IVIG) solution has been shown to increase the time free from serious infection. Kedrion IVIG 10% is a new preparation of an immunoglobulin G (IgG) solution. Kedrion IVIG 10% will be given by IV infusion to all study participants. The data collected will help determine whether Kedrion IVIG 10% is suitable for treating PID subjects.
Interventions
BIOLOGICALKedrion IVIG 10%
Dosage form - Intravenous (IV) infusion of Kedrion IVIG 10%; Dosage - 300 to 900 mg/kg body weight (bw); Frequency - every 21 to 28 days; Treatment duration - 12 months
Sponsors
Kedrion S.p.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed clinical diagnosis of a Primary Immunodeficiency Disease * Male or female, ages 2 to 70 years * Received 300-900 mg/kg of a licensed IVIG therapy at 21 or 28 day intervals for at least 3 months prior to this study * 2 documented IgG trough levels of ≥ 5 g/L are obtained at two infusion cycles (21 or 28 days) within 12 months (one must be within 6 months) prior to study enrolment * Non-pregnant females of child-bearing potential who agree to use adequate birth control during the study * Subject is willing to comply with the protocol * Authorization to access personal health information. * Signed the informed consent form and a child assent form, if appropriate. * If currently participating in a clinical trial with another experimental IVIG may be enrolled if they have received stable IVIG therapy for at least 3 infusion cycles prior to receiving Kedrion IVIG 10% and all inclusion and
Exclusion criteria
are satisfied * If currently participating in a trial of SCIG can be enrolled if they are switched to IVIG for three infusion cycles (21 or 28 days) prior to enrolment in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Acute, Serious Bacterial Infections in the Total ITT Population. | 13 months | The incidence of acute serious bacterial infections, e.g. bacterial pneumonia, bacteremia/sepsis, bacterial meningitis, visceral abscess, osteomyelitis/septic arthritis, meeting EMA and FDA criteria. |
Secondary
| Measure | Time frame |
|---|---|
| Infections Other Than Acute, Serious Bacterial Infections (ASBIs) in the Total ITT Population. | 13 months |
| Days Unable to Perform Normal Daily Activities Due to Infection in the Total ITT Population. | 13 months |
| Days on Therapeutic Antibiotics in the Total ITT Population. | 13 months |
| Days of Unscheduled Visits to Physicians in the Total ITT Population. | 13 months |
| Number of Hospitalizations Due to Infection in ITT Population. | 13 months |
| Days of Hospitalization Due to Infection in the Total ITT Population. | 13 months |
| Days Out of Work/School/Daycare Due to Infection in the Total ITT Population. | 13 months |
| Yearly Hospitalization Duration Due to Infection in the Total ITT Population. | 13 months |
| Distribution of All-cause Hospitalizations in the Total ITT Population. | 13 months |
| Duration of All-cause Hospitalizations | 13 months |
| Distribution of Fever Episodes in the Total ITT Population. | 13 months |
| Duration of Fever Episodes | 13 months |
| IgG Trough Levels at Steady State in the Total ITT Population. | 13 months |
| Yearly Hospitalization Rate Due to Infection in the Total ITT Population. | 13 months |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Kedrion IVIG 10% 21 and 28 Day Infusion Schedule Kedrion IVIG 10% 21 and 28 Day infusion schedule
Kedrion IVIG 10%: Dosage form - Intravenous (IV) infusion of Kedrion IVIG 10%; Dosage - 300 to 900 mg/kg body weight (bw); Frequency - every 21 or 28 days; Treatment duration - 12 months | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Kedrion IVIG 10% 21 and 28 Day Infusion Schedule |
|---|---|
| Age, Categorical <=18 years | 9 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants |
| Age, Continuous | 39.9 years STANDARD_DEVIATION 20.7 |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 44 / 45 |
| serious Total, serious adverse events | 4 / 45 |
Outcome results
Primary
Incidence of Acute, Serious Bacterial Infections in the Total ITT Population.
The incidence of acute serious bacterial infections, e.g. bacterial pneumonia, bacteremia/sepsis, bacterial meningitis, visceral abscess, osteomyelitis/septic arthritis, meeting EMA and FDA criteria.
Time frame: 13 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Incidence of Acute, Serious Bacterial Infections in the Total ITT Population. | 0.04 ASBI's/person-year |
Secondary
Days of Hospitalization Due to Infection in the Total ITT Population.
Time frame: 13 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Days of Hospitalization Due to Infection in the Total ITT Population. | 0.6 days | Standard Deviation 2.21 |
Secondary
Days of Unscheduled Visits to Physicians in the Total ITT Population.
Time frame: 13 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Days of Unscheduled Visits to Physicians in the Total ITT Population. | 0.9 days | Standard Deviation 1.14 |
Secondary
Days on Therapeutic Antibiotics in the Total ITT Population.
Time frame: 13 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Days on Therapeutic Antibiotics in the Total ITT Population. | 23.3 days | Standard Deviation 33.77 |
Secondary
Days Out of Work/School/Daycare Due to Infection in the Total ITT Population.
Time frame: 13 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Days Out of Work/School/Daycare Due to Infection in the Total ITT Population. | 2.8 days | Standard Deviation 6.56 |
Secondary
Days Unable to Perform Normal Daily Activities Due to Infection in the Total ITT Population.
Time frame: 13 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Days Unable to Perform Normal Daily Activities Due to Infection in the Total ITT Population. | 3.4 days | Standard Deviation 6.53 |
Secondary
Distribution of All-cause Hospitalizations in the Total ITT Population.
Time frame: 13 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Distribution of All-cause Hospitalizations in the Total ITT Population. | 1 hospitalization | 1 Participants |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Distribution of All-cause Hospitalizations in the Total ITT Population. | 0 hospitalizations | 41 Participants |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Distribution of All-cause Hospitalizations in the Total ITT Population. | 2 hospitalizations | 2 Participants |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Distribution of All-cause Hospitalizations in the Total ITT Population. | 3 hospitalizations | 1 Participants |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Distribution of All-cause Hospitalizations in the Total ITT Population. | ≥ 4 hospitalizations | 0 Participants |
Secondary
Distribution of Fever Episodes in the Total ITT Population.
Time frame: 13 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Distribution of Fever Episodes in the Total ITT Population. | 2 fever episodes | 2 Participants |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Distribution of Fever Episodes in the Total ITT Population. | 0 fever episodes | 34 Participants |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Distribution of Fever Episodes in the Total ITT Population. | 1 fever episode | 6 Participants |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Distribution of Fever Episodes in the Total ITT Population. | 3 fever episodes | 1 Participants |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Distribution of Fever Episodes in the Total ITT Population. | 4 fever episodes | 1 Participants |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Distribution of Fever Episodes in the Total ITT Population. | 5 fever episodes | 1 Participants |
Secondary
Duration of All-cause Hospitalizations
Time frame: 13 months
Population: The duration of the hospitalizations was measured for each of four subjects who were hospitalized and was calculated dividing by the subject's study duration in days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Duration of All-cause Hospitalizations | 17.8 days | Standard Deviation 12.07 |
Secondary
Duration of Fever Episodes
Time frame: 13 months
Population: The duration of fever episodes was measured for each of eleven subjects who experienced this event.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Duration of Fever Episodes | 6.5 days | Standard Deviation 4.87 |
Secondary
IgG Trough Levels at Steady State in the Total ITT Population.
Time frame: 13 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | IgG Trough Levels at Steady State in the Total ITT Population. | 888 mg/dL | Standard Deviation 197 |
Secondary
Infections Other Than Acute, Serious Bacterial Infections (ASBIs) in the Total ITT Population.
Time frame: 13 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Infections Other Than Acute, Serious Bacterial Infections (ASBIs) in the Total ITT Population. | Upper respiratory tract infection | 0.42 infect./subject's study duration (years) |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Infections Other Than Acute, Serious Bacterial Infections (ASBIs) in the Total ITT Population. | Sinusitis | 0.48 infect./subject's study duration (years) |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Infections Other Than Acute, Serious Bacterial Infections (ASBIs) in the Total ITT Population. | Viral upper respiratory tract infection | 0.15 infect./subject's study duration (years) |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Infections Other Than Acute, Serious Bacterial Infections (ASBIs) in the Total ITT Population. | Bronchitis | 0.11 infect./subject's study duration (years) |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Infections Other Than Acute, Serious Bacterial Infections (ASBIs) in the Total ITT Population. | Nasopharyngitis | 0.11 infect./subject's study duration (years) |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Infections Other Than Acute, Serious Bacterial Infections (ASBIs) in the Total ITT Population. | Rhinitis | 0.11 infect./subject's study duration (years) |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Infections Other Than Acute, Serious Bacterial Infections (ASBIs) in the Total ITT Population. | Acute sinusitis | 0.15 infect./subject's study duration (years) |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Infections Other Than Acute, Serious Bacterial Infections (ASBIs) in the Total ITT Population. | Gastroenteritis viral | 0.09 infect./subject's study duration (years) |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Infections Other Than Acute, Serious Bacterial Infections (ASBIs) in the Total ITT Population. | Herpes zoster | 0.11 infect./subject's study duration (years) |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Infections Other Than Acute, Serious Bacterial Infections (ASBIs) in the Total ITT Population. | Urinary tract infection | 0.11 infect./subject's study duration (years) |
Secondary
Number of Hospitalizations Due to Infection in ITT Population.
Time frame: 13 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Number of Hospitalizations Due to Infection in ITT Population. | 0 hospitalizations | 42 Participants |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Number of Hospitalizations Due to Infection in ITT Population. | 1 hospitalization | 2 Participants |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Number of Hospitalizations Due to Infection in ITT Population. | 2 hospitalizations | 1 Participants |
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Number of Hospitalizations Due to Infection in ITT Population. | ≥ 3 hospitalizations | 0 Participants |
Secondary
Yearly Hospitalization Duration Due to Infection in the Total ITT Population.
Time frame: 13 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Yearly Hospitalization Duration Due to Infection in the Total ITT Population. | 0.55 days | Standard Deviation 2.196 |
Secondary
Yearly Hospitalization Rate Due to Infection in the Total ITT Population.
Time frame: 13 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Kedrion IVIG 10% 21 and 28 Days Infusion Schedule | Yearly Hospitalization Rate Due to Infection in the Total ITT Population. | 0.11 hospitalizations per year | Standard Deviation 0.436 |