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

• Sponsor: Octapharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03988426
• Collaborator: (none)
• Enrollment: 25
• Locations: 5
• Arm: 1
• Actual Duration (Months): 10.7
• Patients Per Site: 5
• Patients Per Site Per Month: 0.5

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Immune Deficiency Disorder	Biological: Octanorm	Phase 3

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

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical Phase 3 Study to Evaluate the Efficacy, Tolerability and Safety of Subcutaneous Human Immunoglobulin (Octanorm) in Patients With Primary Immunodeficiency Diseases.
• Actual Study Start Date: Mar 7, 2017
• Actual Primary Completion Date: Jan 26, 2018
• Actual Study Completion Date: Jan 26, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Serious Bacterial Infections Per Person-Year on Treatment [Primary Treatment Period (24 Weeks)]

   Serious Bacterial Infections defined as bacteraemia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess

Secondary Outcome Measures

1. Number of Patients With Other Infections [Primary Treatment Period (24 Weeks)]

   The number of patients with all infections of any kind or seriousness.

2. Number of Other Infections [Primary Treatment Period (24 Weeks)]

   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.

3. Time to Resolution of Infections [Primary Treatment Period (24 Weeks) and Whole Treatment Period (up to 36 Weeks)]

   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.

4. Number of Participants Using Antibiotics From 0 to > 20 Days [Primary Treatment Period (24 Weeks)]

   Number of patients using antibiotics during the whole treatment period (36 weeks) grouped per number of days with antibiotic usage.

5. Annual Rate of Antibiotic Use [Primary Treatment Period (24 Weeks)]

   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

6. Hospitalizations Due to Infection [Primary Treatment Period (24 Weeks)]

   Number of days spent in hospital due to infection

7. Rate of Hospitalizations Due to Infection [Primary Treatment Period (24 Weeks)]

   Annual Rate of Hospitalizations due to Infection

8. Episodes of Fever [Primary Treatment Period (24 Weeks) and Whole Treatment Period (up to 36 Weeks)]

   Number of episodes of fever

9. Rate of Episodes of Fever [Primary Treatment Period (24 Weeks)]

   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

10. Patients With Days Missed From Work/Study Due to Infections and Treatment [Primary Treatment Period (24 Weeks)]

    Total number of patients who missed days from work or study due to infections or treatment thereof.

11. Changes in the Subscales of the Form-36 Health Survey Scores From Baseline to the End of the Study [Baseline to the end of study (up to 36 weeks)]

    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.

12. Trough Levels of Serum Total IgG [At baseline and at last infusion (week 33)]

    Total IgG trough concentrations were measured in serum samples taken before each infusion given at the study site.

13. Number of Participants Experiencing Treatment-Emergent AEs [Up to 36 weeks]

    TEAEs were classified as temporally associated if the onset was during the infusion or within 72 hours after the end of the infusion.

14. Proportion of Infusions With at Least 1 Temporally Associated AE [Up to 36 weeks]

    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.

15. Total Number of Adverse Events Regardless of Causality [Up to 36 weeks]

    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.

16. Number of Related Adverse Events [Up to 36 weeks]

    A related adverse event is an AE for which a causal relationship between the IMP and the AE cannot be ruled out.

17. Number of Infusions With Infusion Site Reaction [Up to 36 weeks]

    Total number of infusions that triggered an infusion site reaction and number of infusions that triggered mild, moderate, severe or no infusion site reactions.

18. Annual Rate of Infections [Up to 36 weeks]

    The annual rate of all infections of any kind of seriousness

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. Patient must freely give written informed consent.

2. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The State Research Center, Institute of Immunology of the Federal Medical-Biological Agency	Moscow		Russian Federation	115478
2	Federal Research Center of Pediatric Hematology, Oncology and Immunology of the Ministry of Health and Social Development of the Russian Federation	Moscow		Russian Federation	117997
3	State Medical University	Rostov		Russian Federation	344022
4	Pasteur Institute	Saint Petersburg		Russian Federation	197101
5	Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of sciences	Yekaterinburg		Russian Federation	620219

Sponsors and Collaborators

• Octapharma

Investigators

• Study Director: Wolfgang Toeglhofer, MD, Octapharma

Study Documents (Full-Text)

• Study Protocol - Nov 30, 2016
• Statistical Analysis Plan - Mar 23, 2018

More Information

Publications

None provided.

• Responsible Party: Octapharma
• ClinicalTrials.gov Identifier: NCT03988426
• Other Study ID Numbers: SCGAM-04
• First Posted: Jun 17, 2019
• Last Update Posted: Mar 10, 2020
• Last Verified: Feb 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Additional relevant MeSH terms: Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes

Study Results

Participant Flow

Arm/Group Title	Participants Administered Octanorm
Arm/Group Description	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)
Period Title: Overall Study
STARTED	25
COMPLETED	24
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	All Patients
Arm/Group Description	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
Overall Participants	25
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	35.24
Sex: Female, Male (Count of Participants)
Female	15 60%
Male	10 40%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	25 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
Russia	25 100%
Height (centimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters]	170 (8.68)
Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	66.49 (10.54)
BMI (Body Mass Index) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	23.02 (3.48)

Outcome Measures

1. Primary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Octanorm
Arm/Group Description	Octanorm: Octanorm
Measure Participants	24
Number [SBI per patient year]	0

2. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Octanorm
Arm/Group Description	Octanorm: Octanorm
Measure Participants	24
Number of Patients With Infections	14 56%
Number of Patients with 0 Infections	10 40%
Number of Patients with 1 Infection	9 36%
Number of Patients with 2 Infections	2 8%
Number of Patients with 3 Infections	0 0%
Number of Patients with 4 Infections	2 8%
Number of Patients with 5 Infections	1 4%

3. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Patients
Arm/Group Description	Full analysis set
Measure Participants	24
Number of Mild Infections	17
Number of Moderate Infections	9
Number of Severe Infections	0

4. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Octanorm
Arm/Group Description	Octanorm: Octanorm
Measure Participants	24
Primary Treatment Period	9.53
Whole Treatment Period	10.32

5. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Octanorm
Arm/Group Description	Octanorm: Octanorm
Measure Participants	24
Patients with 0 Treatment Days	14 56%
Patients with 5 Treatment Days	2 8%
Patients with 7 Treatment Days	1 4%
Patients with 8 Treatment Days	2 8%
Patients with >20 Treatment Days	5 20%

6. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Octanorm
Arm/Group Description	Octanorm: Octanorm
Measure Participants	24
Number [treatment episodes per person-year]	1.73

7. Secondary Outcome

Title	Hospitalizations Due to Infection
Description	Number of days spent in hospital due to infection
Time Frame	Primary Treatment Period (24 Weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Octanorm
Arm/Group Description	Octanorm: Octanorm
Measure Participants	24
Mean (Standard Deviation) [days]	0 (0)

8. Secondary Outcome

Title	Rate of Hospitalizations Due to Infection
Description	Annual Rate of Hospitalizations due to Infection
Time Frame	Primary Treatment Period (24 Weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Octanorm
Arm/Group Description	Octanorm: Octanorm
Measure Participants	24
Number [hospitalizations/person-year]	0

9. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Octanorm
Arm/Group Description	Octanorm: Octanorm
Measure Participants	24
Primary Treatment Period	6
Whole Treatment Period	8

10. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Octanorm
Arm/Group Description	Octanorm: Octanorm
Measure Participants	24
Number [episodes of fever per person-year]	0.55

11. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Octanorm
Arm/Group Description	Octanorm: Octanorm
Measure Participants	24
Count of Participants [Participants]	3 12%

12. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Full Analysis Set
Arm/Group Description	All participants who received at least 1 complete treatment with Octanorm and for whom any post-baseline data was available.
Measure Participants	25
Physical Functioning	2.5 (12.25)
Role Physical	8.07 (25.83)
Bodily Pain	21.38 (28.12)
General Health	-1.08 (15.16)
Vitality	5.73 (17.67)
Social Functioning	7.81 (23.26)
Role Emotional	10.76 (22.18)
Mental Health	5.83 (20.62)

13. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Octanorm
Arm/Group Description	Octanorm: Octanorm
Measure Participants	25
Screening Draw 1	8.71 (2.68)
Week 33	9.99 (1.79)

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Octanorm
Arm/Group Description	Octanorm: Octanorm
Measure Participants	25
Without Infusion Site Reactions and With Infection	18
Without Infusion Site Reactions/Without Infection	11
Infections (only)	16

15. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Octanorm
Arm/Group Description	Octanorm: Octanorm
Measure Participants	25
Number [proportion of infusions]	.013

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Octanorm
Arm/Group Description	Octanorm: Octanorm
Measure Participants	25
Number [adverse events]	59

17. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Octanorm
Arm/Group Description	Octanorm: Octanorm
Measure Participants	25
Number [related adverse events]	3

18. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Octanorm
Arm/Group Description	Octanorm: Octanorm
Measure Participants	25
Infusions with Mild Local Site Reactions	102
Infusions with Moderate Local Site Reactions	17
Infusions with Severe Local Site Reactions	0
Infusions with No Infusion Site Reaction	659

19. Secondary Outcome

Title	Annual Rate of Infections
Description	The annual rate of all infections of any kind of seriousness
Time Frame	Up to 36 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Patients
Arm/Group Description	Full analysis set
Measure Participants	24
Number [infections/person-year]	2.37

Adverse Events

Time Frame	Up to 36 weeks
Arm/Group Title	Octanorm
Arm/Group Description	Octanorm: Octanorm
All Cause Mortality
	Octanorm
	Affected / at Risk (%)	# Events
Total	0/25 (0%)
Serious Adverse Events
	Octanorm
	Affected / at Risk (%)	# Events
Total	0/25 (0%)
Other (Not Including Serious) Adverse Events
	Octanorm
	Affected / at Risk (%)	# Events
Total	18/25 (72%)
Blood and lymphatic system disorders
Blood and Lymphatic Infection	2/25 (8%)	2
Gastrointestinal disorders
Food Poisoning	2/25 (8%)	2
General disorders
Condition Aggravated	5/25 (20%)	6
Infections and infestations
Respiratory Tract Infection	6/25 (24%)	8
Bronchitis	4/25 (16%)	5
Rhinitis	2/25 (8%)	2
Pharyngitis	2/25 (8%)	2
Investigations
Investigations	2/25 (8%)	2
Nervous system disorders
Dizziness	2/25 (8%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.