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Study to Evaluate the Efficacy, Tolerability and Safety of Octanorm in Patients With Primary Immunodeficiency Diseases

Primary Purpose

Primary Immune Deficiency Disorder

Status
Completed
Phase
Phase 3
Locations
Russian Federation
Study Type
Interventional
Intervention
Octanorm
Sponsored by
Octapharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Immune Deficiency Disorder

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age of ≥18 years and ≤70 years.
  2. Confirmed diagnosis of PI requiring immunoglobulin replacement therapy due to hypogammaglobulinaemia or agammaglobulinaemia. The type of PI should be recorded.
  3. 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).
  4. 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.
  5. 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:

    • Oral, implantable, transdermal or injectable contraceptives
    • Intrauterine device
    • Condoms; diaphragm or vaginal ring with spermicidal jellies or cream
    • Sexual abstinence
    • Vasectomised partner
  6. Patient must freely give written informed consent.
  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 (IV) antibiotic treatment within 2 weeks prior to and during the screening period.
  2. Known history of adverse reactions to Immunoglobulin A 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 of PI, within the past 3 months prior to first infusion of octanorm.
  5. Ongoing history of hypersensitivity or persistent reactions to blood or plasma derived products, or any component of the investigational medicinal product (IMP) (such as Polysorbate 80).
  6. History of malignancies of lymphoid cells and immunodeficiency with lymphoma.
  7. Severe liver function impairment (ALAT 3 times above upper limit of normal).
  8. Known protein-losing enteropathies or proteinuria.
  9. Presence of renal function impairment (creatinine >120 µM/L or creatinine >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).
  10. Treatment with enteral or parenteral steroids for ≥30 days or when given intermittently or as bolus, at daily doses ≥0.15 mg/kg. Inhaled corticosteroids are allowed.
  11. Patients with chronic obstructive pulmonary disease (COPD) stage Global Initiative for Chronic Obstructive Lung Disease (GOLD) III or IV.
  12. Treatment with immunosuppressive 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 IMP 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 human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) infection.
  18. Pregnant or nursing women; planned pregnancy during course of the study

Sites / Locations

  • The State Research Center, Institute of Immunology of the Federal Medical-Biological Agency
  • Federal Research Center of Pediatric Hematology, Oncology and Immunology of the Ministry of Health and Social Development of the Russian Federation
  • State Medical University
  • Pasteur Institute
  • Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of sciences

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Octanorm

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Number of Patients With Other Infections
The number of patients with all infections of any kind or seriousness.
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.
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.
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.
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
Hospitalizations Due to Infection
Number of days spent in hospital due to infection
Rate of Hospitalizations Due to Infection
Annual Rate of Hospitalizations due to Infection
Episodes of Fever
Number of episodes of fever
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
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.
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.
Trough Levels of Serum Total IgG
Total IgG trough concentrations were measured in serum samples taken before each infusion given at the study site.
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.
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.
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.
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.
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.
Annual Rate of Infections
The annual rate of all infections of any kind of seriousness

Full Information

First Posted
June 13, 2019
Last Updated
February 25, 2020
Sponsor
Octapharma
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1. Study Identification

Unique Protocol Identification Number
NCT03988426
Brief Title
Study to Evaluate the Efficacy, Tolerability and Safety of Octanorm in Patients With Primary Immunodeficiency Diseases
Official Title
Clinical Phase 3 Study to Evaluate the Efficacy, Tolerability and Safety of Subcutaneous Human Immunoglobulin (Octanorm) in Patients With Primary Immunodeficiency Diseases.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
March 7, 2017 (Actual)
Primary Completion Date
January 26, 2018 (Actual)
Study Completion Date
January 26, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Octapharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
Clinical phase 3 study to evaluate the efficacy, tolerability and safety of subcutaneous human immunoglobulin (octanorm) in patients with primary immunodeficiency diseases.
Detailed Description
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Immune Deficiency Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Octanorm
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Octanorm
Intervention Description
Octanorm
Primary Outcome Measure Information:
Title
Number of Serious Bacterial Infections Per Person-Year on Treatment
Description
Serious Bacterial Infections defined as bacteraemia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess
Time Frame
Primary Treatment Period (24 Weeks)
Secondary Outcome Measure Information:
Title
Number of Patients With Other Infections
Description
The number of patients with all infections of any kind or seriousness.
Time Frame
Primary Treatment Period (24 Weeks)
Title
Number of Other Infections
Description
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.
Time Frame
Primary Treatment Period (24 Weeks)
Title
Time to Resolution of Infections
Description
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.
Time Frame
Primary Treatment Period (24 Weeks) and Whole Treatment Period (up to 36 Weeks)
Title
Number of Participants Using Antibiotics From 0 to > 20 Days
Description
Number of patients using antibiotics during the whole treatment period (36 weeks) grouped per number of days with antibiotic usage.
Time Frame
Primary Treatment Period (24 Weeks)
Title
Annual Rate of Antibiotic Use
Description
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
Time Frame
Primary Treatment Period (24 Weeks)
Title
Hospitalizations Due to Infection
Description
Number of days spent in hospital due to infection
Time Frame
Primary Treatment Period (24 Weeks)
Title
Rate of Hospitalizations Due to Infection
Description
Annual Rate of Hospitalizations due to Infection
Time Frame
Primary Treatment Period (24 Weeks)
Title
Episodes of Fever
Description
Number of episodes of fever
Time Frame
Primary Treatment Period (24 Weeks) and Whole Treatment Period (up to 36 Weeks)
Title
Rate of Episodes of Fever
Description
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
Time Frame
Primary Treatment Period (24 Weeks)
Title
Patients With Days Missed From Work/Study Due to Infections and Treatment
Description
Total number of patients who missed days from work or study due to infections or treatment thereof.
Time Frame
Primary Treatment Period (24 Weeks)
Title
Changes in the Subscales of the Form-36 Health Survey Scores From Baseline to the End of the Study
Description
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.
Time Frame
Baseline to the end of study (up to 36 weeks)
Title
Trough Levels of Serum Total IgG
Description
Total IgG trough concentrations were measured in serum samples taken before each infusion given at the study site.
Time Frame
At baseline and at last infusion (week 33)
Title
Number of Participants Experiencing Treatment-Emergent AEs
Description
TEAEs were classified as temporally associated if the onset was during the infusion or within 72 hours after the end of the infusion.
Time Frame
Up to 36 weeks
Title
Proportion of Infusions With at Least 1 Temporally Associated AE
Description
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.
Time Frame
Up to 36 weeks
Title
Total Number of Adverse Events Regardless of Causality
Description
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.
Time Frame
Up to 36 weeks
Title
Number of Related Adverse Events
Description
A related adverse event is an AE for which a causal relationship between the IMP and the AE cannot be ruled out.
Time Frame
Up to 36 weeks
Title
Number of Infusions With Infusion Site Reaction
Description
Total number of infusions that triggered an infusion site reaction and number of infusions that triggered mild, moderate, severe or no infusion site reactions.
Time Frame
Up to 36 weeks
Title
Annual Rate of Infections
Description
The annual rate of all infections of any kind of seriousness
Time Frame
Up to 36 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: Oral, implantable, transdermal or injectable contraceptives Intrauterine device Condoms; diaphragm or vaginal ring with spermicidal jellies or cream Sexual abstinence Vasectomised partner 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: Acute infection requiring intravenous (IV) antibiotic treatment within 2 weeks prior to and during the screening period. Known history of adverse reactions to Immunoglobulin A in other products. Patients with body mass index >40 kg/m2 Exposure to blood or any blood product or plasma derivatives, other than IVIG treatment of PI, within the past 3 months prior to first infusion of octanorm. Ongoing history of hypersensitivity or persistent reactions to blood or plasma derived products, or any component of the investigational medicinal product (IMP) (such as Polysorbate 80). History of malignancies of lymphoid cells and immunodeficiency with lymphoma. Severe liver function impairment (ALAT 3 times above upper limit of normal). Known protein-losing enteropathies or proteinuria. Presence of renal function impairment (creatinine >120 µM/L or creatinine >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). Treatment with enteral or parenteral steroids for ≥30 days or when given intermittently or as bolus, at daily doses ≥0.15 mg/kg. Inhaled corticosteroids are allowed. Patients with chronic obstructive pulmonary disease (COPD) stage Global Initiative for Chronic Obstructive Lung Disease (GOLD) III or IV. Treatment with immunosuppressive drugs. Live viral vaccination (such as measles, rubella, mumps and varicella) within the last 2 months prior to first infusion of octanorm. Treatment with any IMP within 3 months prior to first infusion of octanorm. Presence of any condition that is likely to interfere with the evaluation of study medication or satisfactory conduct of the trial. Known or suspected to abuse alcohol, drugs, psychotropic agents or other chemicals within the past 12 months prior to first infusion of octanorm. Known or suspected human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) infection. Pregnant or nursing women; planned pregnancy during course of the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wolfgang Toeglhofer, MD
Organizational Affiliation
Octapharma
Official's Role
Study Director
Facility Information:
Facility Name
The State Research Center, Institute of Immunology of the Federal Medical-Biological Agency
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
Facility Name
Federal Research Center of Pediatric Hematology, Oncology and Immunology of the Ministry of Health and Social Development of the Russian Federation
City
Moscow
ZIP/Postal Code
117997
Country
Russian Federation
Facility Name
State Medical University
City
Rostov
ZIP/Postal Code
344022
Country
Russian Federation
Facility Name
Pasteur Institute
City
Saint Petersburg
ZIP/Postal Code
197101
Country
Russian Federation
Facility Name
Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of sciences
City
Yekaterinburg
ZIP/Postal Code
620219
Country
Russian Federation

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32212944
Citation
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.
Results Reference
derived

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Study to Evaluate the Efficacy, Tolerability and Safety of Octanorm in Patients With Primary Immunodeficiency Diseases

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