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

Clinical Phase 3 Study to Evaluate the Efficacy, Tolerability and Safety of Subcutaneous Human Immunoglobulin (Octanorm) in Patients With Primary Immunodeficiency Diseases.

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

Study Overview

• Status: Completed
• Conditions: Primary Immune Deficiency Disorder
• Intervention / Treatment: Biological: Octanorm

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

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 115478
    • The State Research Center, Institute of Immunology of the Federal Medical-Biological Agency
  • Moscow, Russian Federation, 117997
    • Federal Research Center of Pediatric Hematology, Oncology and Immunology of the Ministry of Health and Social Development of the Russian Federation
  • Rostov, Russian Federation, 344022
    • State Medical University
  • Saint Petersburg, Russian Federation, 197101
    • Pasteur Institute
  • Yekaterinburg, Russian Federation, 620219
    • Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Octanorm; 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.

Biological: Octanorm; Octanorm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Secondary Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: Octapharma
• Investigators: Study Director: Wolfgang Toeglhofer, MD, Octapharma

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2017
• Primary Completion (Actual): January 26, 2018
• Study Completion (Actual): January 26, 2018

Study Registration Dates

• First Submitted: June 13, 2019
• First Submitted That Met QC Criteria: June 14, 2019
• First Posted (Actual): June 17, 2019

Study Record Updates

• Last Update Posted (Actual): March 10, 2020
• Last Update Submitted That Met QC Criteria: February 25, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Genetic Diseases, Inborn; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases
• Other Study ID Numbers: SCGAM-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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