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Clinical phase 3 study to evaluate the efficacy, tolerability and safety of subcutaneous human immunoglobulin (octanorm) in patients with primary immunodeficiency diseases.
Octanorm (cutaquig®) is a 16.5% human normal immunoglobulin solution developed by Octapharma for subcutaneous administration (SCIG). It is supplied as a liquid formulation ready to use. One important therapeutic use of immunoglobulins is to provide antibodies to prevent viral and bacterial diseases (replacement therapy). Children and adults with a Primary Immunodeficiency Disease (PID) have an increased risk of recurrent bacterial and viral infections. These diseases can be severe and can lead to substantial morbidity. Responses to antibacterial therapy are often poor. At present, most primary immune deficiencies are not curable, but SCIGs have been shown to decrease the total number of severe infections and the duration of hospitalization. This study evaluated the efficacy, safety and tolerability of octanorm in adult PID patients in an open-label, multi center, phase 3 study with an 8-week wash-in/wash-out period followed by a 6-month efficacy period
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Octanorm | Experimental | Human Normal Immunoglobulin for Subcutaneous Administration (Octanorm) is a liquid formulation of normal human IgG at a concentration of 16.5% administered as a SC infusion at weekly intervals (either done at the study center [during first training sessions and then for every 4th administration] or at home by the patient or caregiver). The initial weekly dose was determined based on subjects' previous IVIG treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Octanorm | Biological | Octanorm |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Serious Bacterial Infections Per Person-Year on Treatment | Serious Bacterial Infections defined as bacteraemia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess | Primary Treatment Period (24 Weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Other Infections | The number of patients with all infections of any kind or seriousness. | Primary Treatment Period (24 Weeks) |
| Number of Other Infections | For other infections, the Medical Dictionary for Regulatory Activities (MedDRA) preferred term was used to determine the type of infection. They were grouped into the following categories as determined by a medical expert: Ear infections, eye infections, infections of the gastrointestinal tract, infections of the genitourinary tract, upper respiratory tract infections, lower respiratory tract infections, infections of the skin, and infections not elsewhere classified. |
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Inclusion Criteria:
Age of ≥18 years and ≤70 years.
Confirmed diagnosis of PI requiring immunoglobulin replacement therapy due to hypogammaglobulinaemia or agammaglobulinaemia. The type of PI should be recorded.
Patients with at least 4 infusions on regular treatment with any Intravenous Immunoglobulin (IVIG) prior to entering the study. Constant IVIG dose between 200 and 800 mg/kg body weight (the individual doses of the last 4 infusions should not vary by more than ±25% of the mean dose for the last 4 infusions).
Availability of at least 2 IgG trough levels with an IgG level of ≥5.0 g/L from the period of the last 4 IVIG infusions.
Negative result on a pregnancy test (Human Chorionic Gonadotrophin [HCG]-based assay in urine) for women of childbearing potential and use of a reliable method of contraception for the duration of the study. Women of non-childbearing potential must be post-menopausal (amenorrhoeic for at least 12 months) or surgically sterile.
Examples for medically acceptable methods of birth control for this study include:
Patient must freely give written informed consent.
Willingness to comply with all aspects of the protocol, including blood sampling, for the duration of the study.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Wolfgang Toeglhofer, MD | Octapharma | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The State Research Center, Institute of Immunology of the Federal Medical-Biological Agency | Moscow | 115478 | Russia | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32212944 | Derived | Latysheva E, Rodina Y, Sizyakina L, Totolian A, Tuzankina I. Efficacy and safety of octanorm (cutaquig(R)) in adults with primary immunodeficiencies with predominant antibody deficiency: a prospective, open-label study. Immunotherapy. 2020 Apr;12(5):299-309. doi: 10.2217/imt-2020-0012. Epub 2020 Mar 26. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Participants Administered Octanorm | All patients in the study received Octanorm as study drug. Dosage of octanorm was based on the previous dosage of IVIG for each patient: by dividing the previous IVIG dosage by the number of weeks between IVIG administrations. Octanorm was to be administered every week (+/- 2 days) as subcutaneous administration. Administration were either done at the study site (for the first training sessions and then every 4th infusions) or at home (administered by the patient or a caregiver) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Patients | Full analysis set (FAS population) included all patients who received at least one administration of the study drug and for whom any post-baseline data was available |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Serious Bacterial Infections Per Person-Year on Treatment | Serious Bacterial Infections defined as bacteraemia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess | Posted | Number | SBI per patient year | Primary Treatment Period (24 Weeks) |
|
|
Up to 36 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Octanorm | Octanorm: Octanorm | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mikaela Raymond | CRMG | 866-337-1868 | ctgov@clinicalresearchmgt.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 30, 2016 | Jul 17, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 23, 2018 | Jul 17, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000081207 | Primary Immunodeficiency Diseases |
| ID | Term |
|---|---|
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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| Primary Treatment Period (24 Weeks) |
| Time to Resolution of Infections | Since infections were reported as adverse events, the time to resolution of an infection was the time from the start date of the infection adverse event to the end date of the infection adverse event. | Primary Treatment Period (24 Weeks) and Whole Treatment Period (up to 36 Weeks) |
| Number of Participants Using Antibiotics From 0 to > 20 Days | Number of patients using antibiotics during the whole treatment period (36 weeks) grouped per number of days with antibiotic usage. | Primary Treatment Period (24 Weeks) |
| Annual Rate of Antibiotic Use | The number of antibiotic treatment episodes per person-year of treatment was calculated by the following formula: Total number of antibiotic treatment episodes / patient-years of Octanorm treatment | Primary Treatment Period (24 Weeks) |
| Hospitalizations Due to Infection | Number of days spent in hospital due to infection | Primary Treatment Period (24 Weeks) |
| Rate of Hospitalizations Due to Infection | Annual Rate of Hospitalizations due to Infection | Primary Treatment Period (24 Weeks) |
| Episodes of Fever | Number of episodes of fever | Primary Treatment Period (24 Weeks) and Whole Treatment Period (up to 36 Weeks) |
| Rate of Episodes of Fever | The number of episodes of fever per person-year of treatment was calculated by the following formula: Total number of episodes of fever / patient-years of Octanorm treatment | Primary Treatment Period (24 Weeks) |
| Patients With Days Missed From Work/Study Due to Infections and Treatment | Total number of patients who missed days from work or study due to infections or treatment thereof. | Primary Treatment Period (24 Weeks) |
| Changes in the Subscales of the Form-36 Health Survey Scores From Baseline to the End of the Study | The SF-36-HS consists of 36 items organized into 8 subscales. The 8 subscales could be combined into 2 summary scores, physical and mental. The calculated summary scores were transformed to a range of 0-100, where a higher score indicates better health. A positive change score indicates improvement. | Baseline to the end of study (up to 36 weeks) |
| Trough Levels of Serum Total IgG | Total IgG trough concentrations were measured in serum samples taken before each infusion given at the study site. | At baseline and at last infusion (week 33) |
| Number of Participants Experiencing Treatment-Emergent AEs | TEAEs were classified as temporally associated if the onset was during the infusion or within 72 hours after the end of the infusion. | Up to 36 weeks |
| Proportion of Infusions With at Least 1 Temporally Associated AE | The proportion of infusions with at least 1 temporally associated AE (TAAE) was calculated by dividing the total number of TAAE by the total number of infusions. | Up to 36 weeks |
| Total Number of Adverse Events Regardless of Causality | An AE is any untoward medical occurrence in a study patient receiving an IMP and which does not necessarily have a causal relationship with this treatment. | Up to 36 weeks |
| Number of Related Adverse Events | A related adverse event is an AE for which a causal relationship between the IMP and the AE cannot be ruled out. | Up to 36 weeks |
| Number of Infusions With Infusion Site Reaction | Total number of infusions that triggered an infusion site reaction and number of infusions that triggered mild, moderate, severe or no infusion site reactions. | Up to 36 weeks |
| Annual Rate of Infections | The annual rate of all infections of any kind of seriousness | Up to 36 weeks |
| Federal Research Center of Pediatric Hematology, Oncology and Immunology of the Ministry of Health and Social Development of the Russian Federation |
| Moscow |
| 117997 |
| Russia |
| State Medical University | Rostov-on-Don | 344022 | Russia |
| Pasteur Institute | Saint Petersburg | 197101 | Russia |
| Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of sciences | Yekaterinburg | 620219 | Russia |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Height | Mean | Standard Deviation | centimeters |
|
| Weight | Mean | Standard Deviation | kilograms |
|
| BMI (Body Mass Index) | Mean | Standard Deviation | kg/m^2 |
|
|
| Secondary | Number of Patients With Other Infections | The number of patients with all infections of any kind or seriousness. | Posted | Count of Participants | Participants | Primary Treatment Period (24 Weeks) |
|
|
|
| Secondary | Number of Other Infections | For other infections, the Medical Dictionary for Regulatory Activities (MedDRA) preferred term was used to determine the type of infection. They were grouped into the following categories as determined by a medical expert: Ear infections, eye infections, infections of the gastrointestinal tract, infections of the genitourinary tract, upper respiratory tract infections, lower respiratory tract infections, infections of the skin, and infections not elsewhere classified. | Posted | Number | Infections | Primary Treatment Period (24 Weeks) |
|
|
|
| Secondary | Time to Resolution of Infections | Since infections were reported as adverse events, the time to resolution of an infection was the time from the start date of the infection adverse event to the end date of the infection adverse event. | Posted | Number | days | Primary Treatment Period (24 Weeks) and Whole Treatment Period (up to 36 Weeks) |
|
|
|
| Secondary | Number of Participants Using Antibiotics From 0 to > 20 Days | Number of patients using antibiotics during the whole treatment period (36 weeks) grouped per number of days with antibiotic usage. | Posted | Count of Participants | Participants | Primary Treatment Period (24 Weeks) |
|
|
|
| Secondary | Annual Rate of Antibiotic Use | The number of antibiotic treatment episodes per person-year of treatment was calculated by the following formula: Total number of antibiotic treatment episodes / patient-years of Octanorm treatment | Posted | Number | treatment episodes per person-year | Primary Treatment Period (24 Weeks) |
|
|
|
| Secondary | Hospitalizations Due to Infection | Number of days spent in hospital due to infection | Posted | Mean | Standard Deviation | days | Primary Treatment Period (24 Weeks) |
|
|
|
| Secondary | Rate of Hospitalizations Due to Infection | Annual Rate of Hospitalizations due to Infection | Posted | Number | hospitalizations/person-year | Primary Treatment Period (24 Weeks) |
|
|
|
| Secondary | Episodes of Fever | Number of episodes of fever | Posted | Number | episodes of fever | Primary Treatment Period (24 Weeks) and Whole Treatment Period (up to 36 Weeks) |
|
|
|
| Secondary | Rate of Episodes of Fever | The number of episodes of fever per person-year of treatment was calculated by the following formula: Total number of episodes of fever / patient-years of Octanorm treatment | Posted | Number | episodes of fever per person-year | Primary Treatment Period (24 Weeks) |
|
|
|
| Secondary | Patients With Days Missed From Work/Study Due to Infections and Treatment | Total number of patients who missed days from work or study due to infections or treatment thereof. | Posted | Count of Participants | Participants | Primary Treatment Period (24 Weeks) |
|
|
|
| Secondary | Changes in the Subscales of the Form-36 Health Survey Scores From Baseline to the End of the Study | The SF-36-HS consists of 36 items organized into 8 subscales. The 8 subscales could be combined into 2 summary scores, physical and mental. The calculated summary scores were transformed to a range of 0-100, where a higher score indicates better health. A positive change score indicates improvement. | Posted | Mean | Standard Deviation | score on a scale | Baseline to the end of study (up to 36 weeks) |
|
|
|
| Secondary | Trough Levels of Serum Total IgG | Total IgG trough concentrations were measured in serum samples taken before each infusion given at the study site. | Posted | Mean | Standard Deviation | g/L | At baseline and at last infusion (week 33) |
|
|
|
| Secondary | Number of Participants Experiencing Treatment-Emergent AEs | TEAEs were classified as temporally associated if the onset was during the infusion or within 72 hours after the end of the infusion. | Posted | Number | patients | Up to 36 weeks |
|
|
|
| Secondary | Proportion of Infusions With at Least 1 Temporally Associated AE | The proportion of infusions with at least 1 temporally associated AE (TAAE) was calculated by dividing the total number of TAAE by the total number of infusions. | Posted | Number | proportion of infusions | Up to 36 weeks |
|
|
|
| Secondary | Total Number of Adverse Events Regardless of Causality | An AE is any untoward medical occurrence in a study patient receiving an IMP and which does not necessarily have a causal relationship with this treatment. | Posted | Number | adverse events | Up to 36 weeks |
|
|
|
| Secondary | Number of Related Adverse Events | A related adverse event is an AE for which a causal relationship between the IMP and the AE cannot be ruled out. | Posted | Number | related adverse events | Up to 36 weeks |
|
|
|
| Secondary | Number of Infusions With Infusion Site Reaction | Total number of infusions that triggered an infusion site reaction and number of infusions that triggered mild, moderate, severe or no infusion site reactions. | Posted | Number | infusions | Up to 36 weeks |
|
|
|
| Secondary | Annual Rate of Infections | The annual rate of all infections of any kind of seriousness | Posted | Number | infections/person-year | Up to 36 weeks |
|
|
|
| 25 |
| 0 |
| 25 |
| 18 |
| 25 |
| Food Poisoning | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Condition Aggravated | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Respiratory Tract Infection | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Blood and Lymphatic Infection | Blood and lymphatic system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Investigations | Investigations | MedDRA (Unspecified) | Non-systematic Assessment |
|
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| Title | Measurements |
|---|---|
|
|
| Patients with 8 Treatment Days |
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| Patients with >20 Treatment Days |
|
| Title | Measurements |
|---|---|
|
| General Health |
|
| Vitality |
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| Social Functioning |
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| Role Emotional |
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| Mental Health |
|
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| Infusions with No Infusion Site Reaction |
|