Clinical trial NCT01884311: Pharmacokinetics (PK) and Safety of Subgam-VF in Primary Immunodeficiency Diseases
Official title: A Phase III, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics and Safety of Subgam-VF in Primary Immunodeficiency Diseases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Immune Deficiency Disorders
Common Variable Immunodeficiency
X-linked Agammaglobulinaemia
Hyperimmunoglobulin M Syndrome
Keywords: Primary Immune Deficiency Disorders
Common Variable Immunodeficiency
X-linked agammaglobulinaemia
Hyper-IgM Syndrome
Subcutaneous
Immunoglobulins
Lead sponsor: Bio Products Laboratory
Sponsor class: OTHER
First posted: 2013-06-24
Enrollment: 38
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: OTHER

Brief summary: The main objective of the study is to determine the pharmacokinetics profile of Subgam-VF. The secondary objectives are to assess the safety of Subgam-VF and refine the dose adjustment coefficient for Subgam-VF needed for subjects switching from prior intravenous immunoglobulin (IGIV) therapy.

Detailed description: This will be a Phase III, multicenter, open-label, non-randomized study.

Following a screening period, eligible subjects will commence weekly Subgam-VF treatment; this is a 16% subcutaneous IgG product.

Subjects will receive Subgam-VF for 26 weeks during which time safety will be assessed.

After Week 21, PK sampling will commence.

Follow-up visit (one week after the last Subgam-VF infusion, Week 27). All AEs will be monitored up to 28 days after the last Subgam-VF infusion by telephone contact (Week 30).

Subgam-VF will be administered subcutaneously using infusion pumps.

Subjects will be given diaries to record adverse event data as well as any infusions administered at home. In addition there will be a telephone follow up by an appropriately qualified site staff member on day 3 after each site administered and home administered infusion to check for any adverse reactions including infusion site reactions and remind subjects to document these in their subject study diary.

Eligibility criteria: Inclusion criteria:

1. Aged between 2 and 75 years (at time of initial consent).
2. Body Mass Index (BMI) \< 46 for adults (aged 16 years \& older), \& BMI \< 28 for children.
3. Diagnosed with primary immunodeficiency disease e.g. common variable immunodeficiency, X-linked \& autosomal forms of agammaglobulinaemia, hyper-IgM syndrome, Wiskott-Aldrich syndrome.
4. Currently receiving a licensed (or investigational stage III, IIIb) IGIV or SCIG and

   1. IGIV dose is between 300 and 800 mg/kg/month. SCIG dose is between 110 \& 300 mg/kg/week;
   2. Dose is stable for at least the past three months (i.e. consistent mg/kg +/- 5%);
   3. The infusion interval is every 21 or 28 days for IGIV \& seven days for SCIG;
   4. Has a documented trough level of ≥ 6 g/L (600 mg/dL) on current IgG therapy. If not available can be obtained at the screening visit, Visit 1 (Week 0).
5. Female subjects who are (or become) sexually active must practice contraception by using a method of proven reliability for the duration of the study.
6. Females of child-bearing potential, (defined from the onset of menstruation to one year post menopause), must have a negative result on a urine HCG-based pregnancy test.
7. Willing to comply with all aspects of the protocol, including blood sampling, for the duration of the study.
8. Signed an informed consent form. In the case of subjects under the legal age the parent/guardian will sign an informed consent form \& where appropriate the subject will sign an assent form.

Exclusion Criteria:

1. Has a history of any severe anaphylactic reaction to blood or any blood-derived product.
2. Has selective IgA deficiency or has a history of antibodies to IgA.
3. Has clinically significant impairment of cellular or innate immunity at the discretion of the Investigator
4. Has evidence of an active infection at the time of enrolment (i.e. on day of first infusion). Subjects who are asymptomatic but have not completed their course of antibiotics are eligible.
5. Has previously completed or withdrawn from this study.
6. Is currently receiving, or has received, any investigational agent within the prior three months, unless it is an investigational stage III, IIIb IGIV or SCIG.
7. Is pregnant (confirmed by a positive result on an HCG-based pregnancy test) or is nursing.
8. Is positive for any of the following at screening:

   • Serological test for HIV 1\&2, HCV, or HBsAg
9. Has levels at screening greater than 2.5 times the upper limit of normal as defined at the central laboratory of any of the following:

   * Alanine transaminase (ALT)
   * Aspartate transaminase (AST)
10. Has severe renal impairment (defined as serum creatinine greater than two times the upper limit of normal or BUN greater than two times the upper limit of normal for the range of the laboratory doing the analysis); the subject is on dialysis; or has a history of acute renal failure.
11. Is known to abuse alcohol, opiates, psychotropic agents, or other chemicals or drugs, or has done so within the past 12 months.
12. Has a history of DVT, or thrombotic complications of IgG therapy, or a prior diagnosis of thrombophilia.
13. Suffers from any acute or chronic medical condition, (e.g. renal disease or predisposing conditions for renal disease, coronary artery disease, or protein losing state, proteinuria) that the Investigator feels may interfere with the conduct of the study.
14. Has an acquired medical condition, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (ANC \< 1 x 109/L).
15. Is receiving the following medication:

    * Steroids (long-term daily, \> 0.15 mg of prednisone equivalent/kg/day). Requirement for short or intermittent courses of \> 0.15mg/kg/day would not exclude a subject.
    * Immunosuppressive drugs
    * Immunomodulatory drugs
16. If ≥ 18 years of age, has non-controlled arterial hypertension (systolic blood pressure \> 160 mmHg \&/or diastolic blood pressure \> 100 mmHg). For younger subjects refer to current guidelines for diagnosis of blood pressure1.
17. Has anemia (hemoglobin \< 10 g/dL) at screening.
18. Has severe dermatitis that would preclude sites for safe product administration.

Primary outcomes:
measure: Data (Derived From Absolute Concentration) Were Pooled With Historical Data and a Treatment Variable Defined (Subgam-VF or Gammaplex 5% IGIV). Outcome Measure Defined as Log Transformed sAUC0-t Standardized to One Week.
timeFrame: 1 week
Secondary outcomes:
measure: Number of Participants Who Experienced AEs Based on Treatment-emergent AEs (TEAEs)
timeFrame: 30 weeks
measure: Dose Refinement in Switching From Gammaplex 5% IGIV to Subgam-VF
timeFrame: Week 26
measure: Number of Infusion Site Reactions
timeFrame: 30 weeks
Other outcomes:
measure: Population PK Model for IgG in PID Patients for Alternative Dosing Schedules.
timeFrame: 30 months
Locations:
city: Chandler
country: United States
facility: Arizona Allergy Associates
state: Arizona
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: San Diego
country: United States
facility: University of California San Diego-- Rady's Children's Hospital
state: California
city: Centennial
country: United States
facility: Immunoe International Research
state: Colorado
city: North Palm Beach
country: United States
facility: Allergy Associate of the Palm Beaches
state: Florida
city: Chicago
country: United States
facility: Ann and Robert H Lurie Children's Hospital
state: Illinois
city: Minneapolis
country: United States
facility: Cardinal Glennon Children's Medical Center
state: Minnesota
city: Columbus
country: United States
facility: Optimed Research
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Institute of Allergy & Asthma Clinical Research, LLC
state: Oklahoma
city: Hershey
country: United States
facility: Pennsylvania State University
state: Pennsylvania
city: Dallas
country: United States
facility: Dallas Allergy Immunology
state: Texas
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Fairfax
country: United States
facility: O&O Alpan, LLC
state: Virginia
city: Bellingham
country: United States
facility: Bellingham Asthma Allergy Clinic
state: Washington
city: Milwaukee
country: United States
facility: The Medical College of Wisconsin/Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: Bio Products Laboratory Limited
name: Eric Wolford
role: STUDY_DIRECTOR
References: