Clinical trial NCT03988426: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Immune Deficiency Disorder
Lead sponsor: Octapharma
Sponsor class: INDUSTRY
First posted: 2019-06-17
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Number of Serious Bacterial Infections Per Person-Year on Treatment
timeFrame: Primary Treatment Period (24 Weeks)
Secondary outcomes:
measure: Number of Patients With Other Infections
timeFrame: Primary Treatment Period (24 Weeks)
measure: Number of Other Infections
timeFrame: Primary Treatment Period (24 Weeks)
measure: Time to Resolution of Infections
timeFrame: Primary Treatment Period (24 Weeks) and Whole Treatment Period (up to 36 Weeks)
measure: Number of Participants Using Antibiotics From 0 to > 20 Days
timeFrame: Primary Treatment Period (24 Weeks)
measure: Annual Rate of Antibiotic Use
timeFrame: Primary Treatment Period (24 Weeks)
measure: Hospitalizations Due to Infection
timeFrame: Primary Treatment Period (24 Weeks)
measure: Rate of Hospitalizations Due to Infection
timeFrame: Primary Treatment Period (24 Weeks)
measure: Episodes of Fever
timeFrame: Primary Treatment Period (24 Weeks) and Whole Treatment Period (up to 36 Weeks)
measure: Rate of Episodes of Fever
timeFrame: Primary Treatment Period (24 Weeks)
measure: Patients With Days Missed From Work/Study Due to Infections and Treatment
timeFrame: Primary Treatment Period (24 Weeks)
measure: Changes in the Subscales of the Form-36 Health Survey Scores From Baseline to the End of the Study
timeFrame: Baseline to the end of study (up to 36 weeks)
measure: Trough Levels of Serum Total IgG
timeFrame: At baseline and at last infusion (week 33)
measure: Number of Participants Experiencing Treatment-Emergent AEs
timeFrame: Up to 36 weeks
measure: Proportion of Infusions With at Least 1 Temporally Associated AE
timeFrame: Up to 36 weeks
measure: Total Number of Adverse Events Regardless of Causality
timeFrame: Up to 36 weeks
measure: Number of Related Adverse Events
timeFrame: Up to 36 weeks
measure: Number of Infusions With Infusion Site Reaction
timeFrame: Up to 36 weeks
measure: Annual Rate of Infections
timeFrame: Up to 36 weeks
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: The State Research Center, Institute of Immunology of the Federal Medical-Biological Agency
city: Moscow
country: Russian Federation
facility: Federal Research Center of Pediatric Hematology, Oncology and Immunology of the Ministry of Health and Social Development of the Russian Federation
city: Rostov
country: Russian Federation
facility: State Medical University
city: Saint Petersburg
country: Russian Federation
facility: Pasteur Institute
city: Yekaterinburg
country: Russian Federation
facility: Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of sciences
Study officials:
affiliation: Octapharma
name: Wolfgang Toeglhofer, MD
role: STUDY_DIRECTOR
References:
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.