Clinical trial NCT01888484: Study of Octanorm Subcutaneous IG in Patients With PID
Official title: Clinical Phase III Study to Evaluate the Pharmacokinetics, Efficacy, Tolerability and Safety of Subcutaneous Human Immunoglobulin (Octanorm 16.5%) In Patients With Primary Immunodeficiency Diseases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Immune Deficiency Disorder
Keywords: PID
Lead sponsor: Octapharma
Sponsor class: INDUSTRY
First posted: 2013-06-27
Enrollment: 75
Sex: ALL
Minimum age (years): 2
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label phase III study with a 12-week wash-in/wash-out period followed by a 12-month efficacy period. The main goals of the study are to assess the efficacy of octanorm in preventing serious bacterial infections (SBI) compared with historical control data and to evaluate the pharmacokinetic (PK) characteristics of octanorm.


Eligibility criteria: Inclusion Criteria:

1. Age of at least 2 years up to and including 75 years.
2. Confirmed diagnosis of PI as defined by the ESID and PAGID and requiring immunoglobulin replacement therapy due to hypogammaglobulinaemia or agammaglobulinaemia. The exact type of PI should be recorded.
3. Patients with at least 6 infusions on regular treatment with any IVIG, there of a minimum of the last 2 months on the same product prior to entering the study. Constant IVIG dose between 200 and 800 mg/kg body weight (±20% of the mean dose for the last 6 infusions).
4. Availability of the IgG trough levels of 2 previous IVIG infusions before enrollment, and maintenance of greater than or equal to 5.0 g/L in the trough levels of these 2 previous infusions.
5. Negative result on a pregnancy test (HCG-based assay in urine) for women of childbearing potential and use of a reliable method of contraception for the duration of the study.
6. For adult patients: freely given written informed consent. For minor patients: freely given written informed consent from parents/legal guardians and written informed assent from the child/adolescent in accordance with the applicable regulatory requirements.
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 antibiotic treatment within 2 weeks prior to and during the screening period.
2. Known history of adverse reactions to IgA 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 for PID, within the past 3 months prior to the first infusion of octanorm.
5. Ongoing history of hypersensitivity or persistent reactions to blood or plasma derived products, or any component of the investigational product (such as Polysorbate 80).
6. Requirement of any routine premedication for IgG administration.
7. History of malignancies of lymphoid cells and immunodeficiency with lymphoma.
8. Severe liver function impairment (ALAT 3 times above upper limit of normal).
9. Known protein-losing enteropathies or proteinuria.
10. Presence of renal function impairment (creatinine greater than 120 uM/L), or creatinine greater than 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).
11. Treatment with oral or parenteral steroids for greater than or equal to 30 days or when given intermittently or as bolus at daily doses greater than or equal to 0.15 mg/kg.
12. Treatment with immunosuppressive or immunomodulatory 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 investigational medicinal product 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 HIV, HCV, or HBV infection.
18. Pregnant or nursing women.
19. Planned pregnancy during the course of the study.

Primary outcomes:
measure: Rate of SBI Per Person-year
timeFrame: Every 4 weeks until the final evaluation at week 65.
measure: AUC(t) at Steady-State Conditions
timeFrame: Measured at Week 28 before the start of the SC infusion, 10 minutes before the end of the infusion, and at 2 h, 1, 2, 3, 4 and 7 days after the end of the infusion. Calculated and averaged.
Secondary outcomes:
measure: The Annual Rate of All Infections of Any Kind or Seriousness.
timeFrame: Up to 65 weeks
measure: Non-serious Infections
timeFrame: Up to 65 weeks
measure: Cmax of Total IgG and IgG Subclasses
timeFrame: Measured at week 28
measure: Tmax of Total IgG and IgG Subclasses
timeFrame: Measured at Week 28 for all patients, median value was calculated
measure: AUC of Total IgG and IgG Subclasses
timeFrame: Measured at Week 28
measure: Trough Levels of Serum IgG
timeFrame: Measured once at Week 28, seven days after 28th infusion of octanorm
measure: IVIG to Octanorm DCF (Based on the Area Under the Concentration-time Curve [AUCτ])
timeFrame: AUC Measured at Week 28
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Octapharma Research Site
state: Alabama
city: Irvine
country: United States
facility: Octapharma Research Site
state: California
city: San Diego
country: United States
facility: Octapharma Research Site
state: California
city: Centennial
country: United States
facility: Octapharma Research Site
state: Colorado
city: Omaha
country: United States
facility: Octapharma Research Site
state: Nebraska
city: Toledo
country: United States
facility: Octapharma Research Site
state: Ohio
city: Frisco
country: United States
facility: Octapharma Research Site
state: Texas
city: Edmonton
country: Canada
facility: Octapharma Research Site
city: Montreal
country: Canada
facility: Octapharma Research Site
city: Brno
country: Czechia
facility: Octapharma Research Site
city: Olomouc
country: Czechia
facility: Octapharma Research Site
city: Pilsen
country: Czechia
facility: Octapharma Research Site
city: Prague
country: Czechia
facility: Octapharma Research Site
city: Budapest
country: Hungary
facility: Octapharma Research Site
city: Bialystok
country: Poland
facility: Octapharma Research Site
city: Krakow
country: Poland
facility: Octapharma Research Site
city: Krakow
country: Poland
facility: Octapharma Research Site
city: Lublin
country: Poland
facility: Octapharma Research Site
city: Moscow
country: Russian Federation
facility: Octapharma Research Site
city: Saint Petersburg
country: Russian Federation
facility: Octapharma Research Site
city: Yekaterinburg
country: Russian Federation
facility: Octapharma Research Site
city: Bratislava
country: Slovakia
facility: Octapharma Research Site
city: Košice
country: Slovakia
facility: Octapharma Research Site
city: Martin
country: Slovakia
facility: Octapharma Research Site
Study officials:
affiliation: International Medical Director
name: Wolfgang Frenzel
role: STUDY_DIRECTOR
References:
citation: Kobayashi RH, Gupta S, Melamed I, Mandujano JF, Kobayashi AL, Ritchie B, Geng B, Atkinson TP, Rehman S, Turpel-Kantor E, Litzman J. Clinical Efficacy, Safety and Tolerability of a New Subcutaneous Immunoglobulin 16.5% (Octanorm [Cutaquig(R)]) in the Treatment of Patients With Primary Immunodeficiencies. Front Immunol. 2019 Feb 4;10:40. doi: 10.3389/fimmu.2019.00040. eCollection 2019.