Primary Immune Deficiency Disorder
Conditions
Keywords
PID
Brief summary
This is an open-label phase III study with a 12-week wash-in/wash-out period followed by a 12-month efficacy period. The main goals of the study are to assess the efficacy of octanorm in preventing serious bacterial infections (SBI) compared with historical control data and to evaluate the pharmacokinetic (PK) characteristics of octanorm.
Interventions
BIOLOGICALoctanorm 16.5%
octanorm 16.5%, human normal immunoglobulin for subcutaneous (SC) administration.
Sponsors
Octapharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age of at least 2 years up to and including 75 years. 2. Confirmed diagnosis of PI as defined by the ESID and PAGID and requiring immunoglobulin replacement therapy due to hypogammaglobulinaemia or agammaglobulinaemia. The exact type of PI should be recorded. 3. Patients with at least 6 infusions on regular treatment with any IVIG, there of a minimum of the last 2 months on the same product prior to entering the study. Constant IVIG dose between 200 and 800 mg/kg body weight (±20% of the mean dose for the last 6 infusions). 4. Availability of the IgG trough levels of 2 previous IVIG infusions before enrollment, and maintenance of greater than or equal to 5.0 g/L in the trough levels of these 2 previous infusions. 5. Negative result on a pregnancy test (HCG-based assay in urine) for women of childbearing potential and use of a reliable method of contraception for the duration of the study. 6. For adult patients: freely given written informed consent. For minor patients: freely given written informed consent from parents/legal guardians and written informed assent from the child/adolescent in accordance with the applicable regulatory requirements. 7. Willingness to comply with all aspects of the protocol, including blood sampling, for the duration of the study.
Exclusion criteria
1. Acute infection requiring intravenous antibiotic treatment within 2 weeks prior to and during the screening period. 2. Known history of adverse reactions to IgA in other products. 3. Patients with body mass index ≥40 kg/m2. 4. Exposure to blood or any blood product or plasma derivatives, other than IVIG treatment for PID, within the past 3 months prior to the first infusion of octanorm. 5. Ongoing history of hypersensitivity or persistent reactions to blood or plasma derived products, or any component of the investigational product (such as Polysorbate 80). 6. Requirement of any routine premedication for IgG administration. 7. History of malignancies of lymphoid cells and immunodeficiency with lymphoma. 8. Severe liver function impairment (ALAT 3 times above upper limit of normal). 9. Known protein-losing enteropathies or proteinuria. 10. Presence of renal function impairment (creatinine greater than 120 uM/L), or creatinine greater than 1.35 mg/dL), or predisposition for acute renal failure (e.g., any degree of pre-existing renal insufficiency or routine treatment with known nephritic drugs). 11. Treatment with oral or parenteral steroids for greater than or equal to 30 days or when given intermittently or as bolus at daily doses greater than or equal to 0.15 mg/kg. 12. Treatment with immunosuppressive or immunomodulatory drugs. 13. Live viral vaccination (such as measles, rubella, mumps and varicella) within the last 2 months prior to first infusion of octanorm. 14. Treatment with any investigational medicinal product within 3 months prior to first infusion of octanorm. 15. Presence of any condition, that is likely to interfere with the evaluation of study medication or satisfactory conduct of the trial. 16. Known or suspected to abuse alcohol, drugs, psychotropic agents or other chemicals within the past 12 months prior to first infusion of octanorm. 17. Known or suspected HIV, HCV, or HBV infection. 18. Pregnant or nursing women. 19. Planned pregnancy during the course of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of SBI Per Person-year | Every 4 weeks until the final evaluation at week 65. | The primary efficacy outcome is the rate of SBI (Serious bacterial infections - defined as bacteremia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess) per person-year on treatment. |
| AUC(t) at Steady-State Conditions | Measured at Week 28 before the start of the SC infusion, 10 minutes before the end of the infusion, and at 2 h, 1, 2, 3, 4 and 7 days after the end of the infusion. Calculated and averaged. | The primary endpoint with respect to the PK investigations is the area under the curve AUC(t) (i.e., AUC from time 0 (start of the infusion) to the end of the nominal dosing period, standardised to 1 week) at PKSC2 at steady-state conditions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Total IgG and IgG Subclasses | Measured at week 28 | Cmax (Maximum Plasma Concentration) of total IgG and IgG Subclasses, where the mean value was calculated and reported |
| Tmax of Total IgG and IgG Subclasses | Measured at Week 28 for all patients, median value was calculated | Tmax (Time to Maximum Plasma Concentration) of total IgG and IgG Subclasses |
| The Annual Rate of All Infections of Any Kind or Seriousness. | Up to 65 weeks | The annual rate of all infections of any kind or seriousness. |
| Trough Levels of Serum IgG | Measured once at Week 28, seven days after 28th infusion of octanorm | Trough levels of serum IgG, IgG1, IgG2, IgG3, IgG4 at PK 7 days after 28th infusion of octanorm measured for all patients and median value was calculated and reported |
| IVIG to Octanorm DCF (Based on the Area Under the Concentration-time Curve [AUCτ]) | AUC Measured at Week 28 | IVIG to Octanorm Dose Conversion Factor (based on the area under the concentration-time curve \[AUCτ\]) -- determined by least-squares regression Model which was without restriction of the intercept. |
| AUC of Total IgG and IgG Subclasses | Measured at Week 28 | AUC (Area Under the Concentration-Time Curve) of total IgG and IgG Subclasses calculated for all patients and mean value was calculated and reported |
| Non-serious Infections | Up to 65 weeks | Non-serious infections (total and by category). |
Countries
Canada, Czechia, Hungary, Poland, Russia, Slovakia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Patients All patients.
The data are reported as the overall population as it was not the intent of the protocol to report analysis by age group | 75 |
| Total | 75 |
Baseline characteristics
| Characteristic | All Patients |
|---|---|
| Age, Continuous | 27.81 years STANDARD_DEVIATION 21.911 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 75 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 74 Participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 75 |
| other Total, other adverse events | 61 / 75 |
| serious Total, serious adverse events | 9 / 75 |
Outcome results
Primary
AUC(t) at Steady-State Conditions
The primary endpoint with respect to the PK investigations is the area under the curve AUC(t) (i.e., AUC from time 0 (start of the infusion) to the end of the nominal dosing period, standardised to 1 week) at PKSC2 at steady-state conditions.
Time frame: Measured at Week 28 before the start of the SC infusion, 10 minutes before the end of the infusion, and at 2 h, 1, 2, 3, 4 and 7 days after the end of the infusion. Calculated and averaged.
Population: In several cases, AUCτ could not be calculated due to very flat time-concentration profiles.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Patients | AUC(t) at Steady-State Conditions | 2232.61 h*g/L | Standard Deviation 585.842 |
Primary
Rate of SBI Per Person-year
The primary efficacy outcome is the rate of SBI (Serious bacterial infections - defined as bacteremia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess) per person-year on treatment.
Time frame: Every 4 weeks until the final evaluation at week 65.
Population: The data are reported as the overall population as it was not the intent of the protocol to report analysis by age group
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients | Rate of SBI Per Person-year | 0 SBIs per person year |
Secondary
AUC of Total IgG and IgG Subclasses
AUC (Area Under the Concentration-Time Curve) of total IgG and IgG Subclasses calculated for all patients and mean value was calculated and reported
Time frame: Measured at Week 28
Population: The data are reported as the overall population as it was not the intent of the protocol to report analysis by age group. Data not available for all patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients | AUC of Total IgG and IgG Subclasses | IgG3 AUC | 48.65 hr*g/L | Standard Deviation 18.455 |
| All Patients | AUC of Total IgG and IgG Subclasses | IgG4 AUC | 71.40 hr*g/L | Standard Deviation 102.578 |
| All Patients | AUC of Total IgG and IgG Subclasses | IgG Total AUC | 2232.61 hr*g/L | Standard Deviation 585.842 |
| All Patients | AUC of Total IgG and IgG Subclasses | IgG1 AUC | 1424.69 hr*g/L | Standard Deviation 298.776 |
| All Patients | AUC of Total IgG and IgG Subclasses | IgG2 AUC | 659.57 hr*g/L | Standard Deviation 262.295 |
Secondary
Cmax of Total IgG and IgG Subclasses
Cmax (Maximum Plasma Concentration) of total IgG and IgG Subclasses, where the mean value was calculated and reported
Time frame: Measured at week 28
Population: The data are reported as the overall population as it was not the intent of the protocol to report analysis by age group. Data not available for all patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Patients | Cmax of Total IgG and IgG Subclasses | IgG Total Cmax | 13.47 g/L | Standard Deviation 3.655 |
| All Patients | Cmax of Total IgG and IgG Subclasses | IgG1 Cmax | 8.56 g/L | Standard Deviation 1.858 |
| All Patients | Cmax of Total IgG and IgG Subclasses | IgG2 Cmax | 3.88 g/L | Standard Deviation 1.532 |
| All Patients | Cmax of Total IgG and IgG Subclasses | IgG3 Cmax | 0.32 g/L | Standard Deviation 0.127 |
| All Patients | Cmax of Total IgG and IgG Subclasses | IgG4 Cmax | 0.40 g/L | Standard Deviation 0.567 |
Secondary
IVIG to Octanorm DCF (Based on the Area Under the Concentration-time Curve [AUCτ])
IVIG to Octanorm Dose Conversion Factor (based on the area under the concentration-time curve \[AUCτ\]) -- determined by least-squares regression Model which was without restriction of the intercept.
Time frame: AUC Measured at Week 28
Population: The data are reported as the overall population as it was not the intent of the protocol to report analysis by age group. Data not available for all patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Patients | IVIG to Octanorm DCF (Based on the Area Under the Concentration-time Curve [AUCτ]) | 1.278 unitless | Standard Deviation 0.9401 |
Secondary
Non-serious Infections
Non-serious infections (total and by category).
Time frame: Up to 65 weeks
Population: The data are reported as the overall population as it was not the intent of the protocol to report analysis by age group
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Patients | Non-serious Infections | Eye infections | 3 infections |
| All Patients | Non-serious Infections | Infections of the GI tract | 25 infections |
| All Patients | Non-serious Infections | Infections of the genitourinary tract | 24 infections |
| All Patients | Non-serious Infections | Upper respiratory tract infections | 179 infections |
| All Patients | Non-serious Infections | Lower respiratory tract infections | 32 infections |
| All Patients | Non-serious Infections | Infections of the skin | 6 infections |
| All Patients | Non-serious Infections | Ear infections | 8 infections |
| All Patients | Non-serious Infections | Infections not (elsewhere) classified | 16 infections |
Secondary
The Annual Rate of All Infections of Any Kind or Seriousness.
The annual rate of all infections of any kind or seriousness.
Time frame: Up to 65 weeks
Population: The data are reported as the overall population as it was not the intent of the protocol to report analysis by age group
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients | The Annual Rate of All Infections of Any Kind or Seriousness. | 3.414 infections per person-year |
Secondary
Tmax of Total IgG and IgG Subclasses
Tmax (Time to Maximum Plasma Concentration) of total IgG and IgG Subclasses
Time frame: Measured at Week 28 for all patients, median value was calculated
Population: The data are reported as the overall population as it was not the intent of the protocol to report analysis by age group. Data not available for all patients.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| All Patients | Tmax of Total IgG and IgG Subclasses | Tmax Total IgG | 49.62 hours |
| All Patients | Tmax of Total IgG and IgG Subclasses | Tmax IgG1 | 50.50 hours |
| All Patients | Tmax of Total IgG and IgG Subclasses | Tmax IgG2 | 72.20 hours |
| All Patients | Tmax of Total IgG and IgG Subclasses | Tmax IgG3 | 49.62 hours |
| All Patients | Tmax of Total IgG and IgG Subclasses | Tmax IgG4 | 47.50 hours |
Secondary
Trough Levels of Serum IgG
Trough levels of serum IgG, IgG1, IgG2, IgG3, IgG4 at PK 7 days after 28th infusion of octanorm measured for all patients and median value was calculated and reported
Time frame: Measured once at Week 28, seven days after 28th infusion of octanorm
Population: The data are reported as the overall population as it was not the intent of the protocol to report analysis by age group. Data not available for all patients.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| All Patients | Trough Levels of Serum IgG | Total IgG | 11.85 g/L |
| All Patients | Trough Levels of Serum IgG | IgG1 | 7.51 g/L |
| All Patients | Trough Levels of Serum IgG | IgG2 | 3.12 g/L |
| All Patients | Trough Levels of Serum IgG | IgG3 | 0.27 g/L |
| All Patients | Trough Levels of Serum IgG | IgG4 | 0.15 g/L |