Primary Immune Deficiency DisorderPhase 3NCT03988426
Study to Evaluate the Efficacy, Tolerability and Safety of Octanorm in Patients With Primary Immunodeficiency Diseases
A Phase 3 study testing Octanorm in people with Primary Immune Deficiency Disorder, run by Octapharma at 5 sites in Russia.
Trial summary
Clinical phase 3 study to evaluate the efficacy, tolerability and safety of subcutaneous human immunoglobulin (octanorm) in patients with primary immunodeficiency diseases. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Primary Immune Deficiency Disorder
- What is being tested?
- Octanorm
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 5 sitesRussia
- Study dates
- 7 Mar 2017to 26 Jan 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
Show all 18Show fewer
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Russia5 sites
The State Research Center, Institute of Immunology of the Federal Medical-Biological Agency
Moscow, 115478
Federal Research Center of Pediatric Hematology, Oncology and Immunology of the Ministry of Health and Social Development of the Russian Federation
Moscow, 117997
State Medical University
Rostov-on-Don, 344022
Pasteur Institute
Saint Petersburg, 197101
Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of sciences
Yekaterinburg, 620219
About this study
Official title: 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.
Read the 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
- Conditions
- Primary Immune Deficiency Disorder
- Being tested
- Octanorm
- Medical subject headings
- Primary Immunodeficiency Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OctanormBiological
Octanorm
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Octanorm |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Primary Treatment Period (24 Weeks)
Secondary outcomes (18)
Number of Patients With Other Infections
The number of patients with all infections of any kind or seriousness.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: Primary Treatment Period (24 Weeks)
Hospitalizations Due to Infection
Number of days spent in hospital due to infection
Measured: Primary Treatment Period (24 Weeks)
Rate of Hospitalizations Due to Infection
Annual Rate of Hospitalizations due to Infection
Measured: Primary Treatment Period (24 Weeks)
Episodes of Fever
Number of episodes of fever
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 36 weeks
Annual Rate of Infections
The annual rate of all infections of any kind of seriousness
Measured: Up to 36 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2019
- Study start7 Mar 2017
- Primary completion26 Jan 2018
- Study completion26 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary Immune Deficiency DisorderStudies of the same condition, open and under way.
- More trials run by OctapharmaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Octapharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Wolfgang Toeglhofer, MD, Study director, Octapharma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03988426
- Sponsor's protocol ID
- SCGAM-04
- Status last verified
- Feb 2020
- First submitted
- 13 Jun 2019
- Last updated
- 10 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 32212944
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Phase 3 Study to Evaluate the Efficacy, Tolerability and Safety of Subcutaneous Human Immunoglobulin (Octanorm) in Patients With Primary Immunodeficiency Diseases.
- ClinicalTrials.gov ID
- NCT03988426
- Acronym / sponsor ID
- SCGAM-04
- Conditions
- Primary Immune Deficiency Disorder
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- OctapharmaIndustry (pharma, biotech, devices)
- Study start
- 7 Mar 2017 (actual)
- Primary completion
- 26 Jan 2018 (actual)
- Study completion
- 26 Jan 2018 (actual)
- First posted
- 17 Jun 2019 (actual)
- Results
- Posted 10 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Octanorm | Experimental | Biological: OctanormHuman 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (18 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OctanormOctanorm | Biological | Octanorm |
Primary outcome
Number of Serious Bacterial Infections Per Person-Year on Treatment
Time frame: Primary Treatment Period (24 Weeks)
Serious Bacterial Infections defined as bacteraemia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess
18 secondary outcomes
Number of Patients With Other Infections
Time frame: Primary Treatment Period (24 Weeks)
Number of Other Infections
Time frame: Primary Treatment Period (24 Weeks)
Time to Resolution of Infections
Time frame: Primary Treatment Period (24 Weeks) and Whole Treatment Period (up to 36 Weeks)
Number of Participants Using Antibiotics From 0 to > 20 Days
Time frame: Primary Treatment Period (24 Weeks)
Annual Rate of Antibiotic Use
Time frame: Primary Treatment Period (24 Weeks)
Hospitalizations Due to Infection
Time frame: Primary Treatment Period (24 Weeks)
Rate of Hospitalizations Due to Infection
Time frame: Primary Treatment Period (24 Weeks)
Episodes of Fever
Time frame: Primary Treatment Period (24 Weeks) and Whole Treatment Period (up to 36 Weeks)
Rate of Episodes of Fever
Time frame: Primary Treatment Period (24 Weeks)
Patients With Days Missed From Work/Study Due to Infections and Treatment
Time frame: Primary Treatment Period (24 Weeks)
Changes in the Subscales of the Form-36 Health Survey Scores From Baseline to the End of the Study
Time frame: Baseline to the end of study (up to 36 weeks)
Trough Levels of Serum Total IgG
Time frame: At baseline and at last infusion (week 33)
Number of Participants Experiencing Treatment-Emergent AEs
Time frame: Up to 36 weeks
Proportion of Infusions With at Least 1 Temporally Associated AE
Time frame: Up to 36 weeks
Total Number of Adverse Events Regardless of Causality
Time frame: Up to 36 weeks
Number of Related Adverse Events
Time frame: Up to 36 weeks
Number of Infusions With Infusion Site Reaction
Time frame: Up to 36 weeks
Annual Rate of Infections
Time frame: Up to 36 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32212944Latysheva 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wolfgang Toeglhofer, MD study director
Octapharma
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Octanorm in people with Primary Immune Deficiency Disorder, run by Octapharma at 5 sites in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Serious Bacterial Infections Per Person-Year on Treatment (time frame: Primary Treatment Period (24 Weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03988426, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2020.