Medical Department Plasma Products

Contact person: Paul F.W. Strengers MD

The Medical Department is, in its applied research activities, responsible for the design and conduct of clinical trials with (recently developed) plasma products. The Medical Department closely cooperates with clinical investigators in the Netherlands e.g. the Netherlands Inter-University Working Party on the Study of Immune Deficiencies and the Dutch Haemophilia Treatment Centers, and with investigators abroad.

In 2010, three clinical studies with intravenous immunoglobulin, Nanogam®, were ongoing in order to study the efficacy and safety of Nanogam® in different clinical conditions. Moreover, a clinical study with apotransferrin was initiated, and preparations were made for a clinical study with a newly developed FVIII product.

More information about Nanogram® and other products is available on the page of Plasma Products.

Our activities:

 

Clinical studies with intravenous immunoglobulin product (IVIG), Nanogam®

IVIG treatment in patients with recurrent infections and IgG subclass deficiency, and/or deficient anti-polysaccharide antibody response

This multi-centre, prospective, randomized-controlled, open-label, cross-over clinical trial is performed in cooperation with the Netherlands Inter-University Working Party on the Study of Immune Deficiencies. The aim of the study is to investigate the efficacy of Nanogam® in comparison with antibiotics in the treatment of recurrent (upper respiratory tract) infections in patients with IgG-subclass deficiency or a deficient anti-polysaccharide antibody response.

Patients are randomized to receive either prophylactic co-trimoxazol for 12 months and Nanogam treatment for 12 months, or vice versa. Between the two treatments, a wash-out period of 3 months is included (total study period per patient: 2 years and 3 months). The study is divided into two parts: treatment of adults, and of children ( 5 years). Eight hospitals in the Netherlands participate in the trial. The number of patients to be included is 55 adults and 15/20 children. The inclusion period is 4 years.

The study in adult patients has started in 2007; the first child was included in March 2009. The results of this study will be used for compiling a protocol for the optimal treatment of patients with these disorders.

IVIG therapy for patients with idiopathic cardiomyopathy and endomyocardial Parvovirus B19 persistence (a prospective, double-blind, randomized, placebo-controlled clinical trial

Coordinating investigator: prof. S. Heymans, MUMC, Maastricht
In this prospective, double-blind, randomized, placebo-controlled, single-centre, investigator-initiated study (coordinating investigator: prof S Heymans, MUMC, Maastricht), 50 patients with idiopathic cardiomyopathy and endomyocardial PVB19 persistence are included, and the effect of Nanogam® on virus presence and cardiac functional capacity before and 6 months after IVIg therapy are evaluated.

The patients are randomized to receive either Nanogam® or placebo (G.P.O. ®) additionally to their standard heart failure treatment regimen. Administration of study medication is blinded. The inclusion period is 4 years. The first patient was included in November 2009.

Second IVIG Dose in GBS patients with poor prognosis

(Initiator: prof P.A. van Doorn, Erasmus MC, Rotterdam)
In this multi-centre, prospective, randomized, placebo-controlled, investigator-initiated study (initiator: prof. P.A. van Doorn, Erasmus MC, Rotterdam) which takes place in 72 hospitals in the Netherlands, it is investigated whether patients with Gullian Barré Syndrome (GBS) with the poorest prognosis may benefit from a second course of IVIG when the product is administered within the first weeks after onset of disease, when nerve damage is most likely still reversible.

The first (or only) IVIG course is the standard treatment for GBS patients who are unable to walk and who are still within the first two weeks from onset of weakness, independent of age of the patient or severity of disease. The patients with a poor prognosis are randomized to receive either Nanogam® or placebo (G.P.O. ®). In total 174 patients will be included (poor and good prognosis) in order to treat 87 patient with a second course (poor prognosis). Inclusion period is 3 years; follow-up period per patient 6 months. The first patient was included in February 2010.  

 

Clinical dose escalating study with apotransferrin in order to evaluate the pharmacokinetics, efficacy and safety of the product in patients with atransferrinemia

Atransferrinemia is a very rare disorder, which is caused by a deficiency of the plasma protein transferrin. In the literature, only fourteen patients in twelve families have been reported. No regular treatment is available for these patients. Very low levels of transferrin cause iron accumulation and tissue-damage by radical formation. In addition, free iron promotes growth of bacteria and fungi resulting in an increased number of infections. Moreover, the low levels of transferring results in reduced delivery of iron to the bone marrow and induces reduced haemoglobin synthesis, which consequently leads to anemia.

In this phase II/III prospective, dose-escalating, open-label study, apotransferrin replacement therapy in atransferrinemia patients is assessed. The objective of the study is to investigate the pharmacokinetics, efficacy and safety of apotransferrin. All available patients with atransferrinemia will be included and followed for two years. The primary efficacy parameters are the concentration of transferrin, ferritin and iron in serum as well as the level of transferrin saturation and total iron binding capacity. The patients will be intensively monitored to ensure safety.

Currently one patient in the Vall d’Hebron hospital in Barcelona, Spain is participating in the study. Preparations are made in order to include two children in the Aschaffenburg hospital, Germany.  

 

Safety and efficacy of FVIII-SD/UVC/DH in patients with hemophilia A

A new SD-treated, UVC-illuminated, Dry-heated intermediate purity Factor VIII/von Willebrand Factor concentrate is being developed. A major safety concern for any new FVIII product is the potential immunogenicity of the factor VIII molecule.

Preclinical studies are being designed to investigate whether the virus removal steps, in particular the UVC-illumination technique, have any effects on the FVIII molecule. Further, four clinical prospective, open-label, studies have been designed for multi-center studies in order to evaluate the pharmacokinetics (PK), clinical efficacy and safety of FVIII-SD/UVC/DH in patients with hemophilia A, during both long-term follow-up and surgical interventions. When both in vitro and in vivo studies have shown that potential immunogenicity of the FVIII molecule is not present, the clinical studies will start at the end of 2011.

 

Last edited on: 12 April 2012