Pharmacokinetics (PK) and Safety of Subgam-VF in Primary Immunodeficiency Diseases

Phase 3

Completed

Conditions: X-linked Agammaglobulinaemia
Primary Immune Deficiency Disorders
Common Variable Immunodeficiency
Hyperimmunoglobulin M Syndrome

Interventions: Biological: Subgam

Registration Number: NCT01884311

Lead Sponsor: Bio Products Laboratory

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 38

Inclusion Criteria

Not provided

Exclusion Criteria

Has a history of any severe anaphylactic reaction to blood or any blood-derived product.
Has selective IgA deficiency or has a history of antibodies to IgA.
Has clinically significant impairment of cellular or innate immunity at the discretion of the Investigator
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.
Has previously completed or withdrawn from this study.
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.
Is pregnant (confirmed by a positive result on an HCG-based pregnancy test) or is nursing.
Is positive for any of the following at screening:

• Serological test for HIV 1&2, HCV, or HBsAg
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)
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.
Is known to abuse alcohol, opiates, psychotropic agents, or other chemicals or drugs, or has done so within the past 12 months.
Has a history of DVT, or thrombotic complications of IgG therapy, or a prior diagnosis of thrombophilia.
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.
Has an acquired medical condition, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (ANC < 1 x 109/L).
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
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.
Has anemia (hemoglobin < 10 g/dL) at screening.
Has severe dermatitis that would preclude sites for safe product administration.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Subgam-VF	Subgam	Subgam-VF is a 16% IgG and will be administered weekly, by subcutaneous infusion. The total duration of treatment will be for 26 weeks.

Primary Outcome Measures

Name	Time	Method
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.	1 week	Log transformed sAUC0-t, (AUC0-t standardized to one week) were analysed using a multiple linear regression model fitted including treatment, allowing for variability between treatment groups. The mean difference (Subgam-VF or Gammaplex IGIV 5%) between treatments with 90% Confidence Interval (CI) were back transformed to give an estimate of the ratio (Subgam-VF/ Gammaplex 5% IGIV) of sAUC(0-t). Data was collected at the following timepoints after week 21 of the clinical trial over a period of 1 week: Pre-dose on Day 0 and post-dose at days 1, 2, 3, 5 and 7.

Secondary Outcome Measures

Name	Time	Method
Number of Infusion Site Reactions	30 weeks	Infusion site reactions are defined as those events with onset date between the first infusion date and 28 days after the last infusion.
Dose Refinement in Switching From Gammaplex 5% IGIV to Subgam-VF	Week 26	The initial weekly dose of Subgam-VF administered was calculated by taking the average weekly equivalent of the subject's IGIV dose, divided by the average dosing interval in weeks (i.e. 3 or 4), multiplied by 1.37, a dose adjustment coefficient based on other licensed subcutaneous IgG products. If the subject was already receiving a weekly SCIG IgG there will be no dose adjustment. A refined dose adjustment was estimated as 1.37/the ratio (Subgam-VF/ Gammaplex 5% IGIV) of geometric means for sAUC0-t and presented with 90% CI.
Number of Participants Who Experienced AEs Based on Treatment-emergent AEs (TEAEs)	30 weeks	TEAEs defined as those events with onset date between the first infusion date and 28 days after the last infusion.

Trial Locations

Locations (16): Arizona Allergy Associates
🇺🇸
Chandler, Arizona, United States
Immunoe International Research
🇺🇸
Centennial, Colorado, United States
Allergy Associate of the Palm Beaches
🇺🇸
North Palm Beach, Florida, United States
Pennsylvania State University
🇺🇸
Hershey, Pennsylvania, United States
AARA Research Center
🇺🇸
Dallas, Texas, United States
Dallas Allergy Immunology
🇺🇸
Dallas, Texas, United States
O&O Alpan, LLC
🇺🇸
Fairfax, Virginia, United States
Bellingham Asthma Allergy Clinic
🇺🇸
Bellingham, Washington, United States
University of California, Irvine
🇺🇸
Irvine, California, United States
The Medical College of Wisconsin/Children's Hospital of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Optimed Research
🇺🇸
Columbus, Ohio, United States
Oklahoma Institute of Allergy & Asthma Clinical Research, LLC
🇺🇸
Oklahoma City, Oklahoma, United States
University of Utah
🇺🇸
Salt Lake City, Utah, United States
University of California San Diego-- Rady's Children's Hospital
🇺🇸
San Diego, California, United States
Cardinal Glennon Children's Medical Center
🇺🇸
Minneapolis, Minnesota, United States
Ann and Robert H Lurie Children's Hospital
🇺🇸
Chicago, Illinois, United States