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Recombinant factor IX Fc fusion protein in children with haemophilia B (Kids B-LONG): results from a multicentre, non-randomised phase 3 study. 2017

Kathelijn Fischer, and Roshni Kulkarni, and Beatrice Nolan, and Johnny Mahlangu, and Savita Rangarajan, and Giulia Gambino, and Lei Diao, and Alejandra Ramirez-Santiago, and Glenn F Pierce, and Geoffrey Allen
Van Creveldkliniek, University Medical Center Utrecht, Utrecht, Netherlands.

BACKGROUND Kids B-LONG was a multicentre, open-label, phase 3 study assessing the safety, efficacy, and pharmacokinetics of recombinant factor IX Fc fusion protein (rFIXFc) in previously treated paediatric patients younger than 12 years with severe haemophilia B. METHODS The study enrolled 30 previously treated boys younger than 12 years with haemophilia B (≤2 IU/dL [≤2%] endogenous coagulation factor IX [FIX] activity). All patients were initially given rFIXFc prophylaxis (50-60 IU/kg) once per week with adjustments to dose (≤100 IU/kg per infusion) or dosing frequency (up to two times per week) as needed. The primary outcome measure was development of inhibitors (neutralising antibodies). Secondary outcomes were pharmacokinetics, annual bleeding rate (ABR), spontaneous joint ABR, the number of infusions and dose required to resolve a bleed, time from last infusion of rFIXFc to a bleeding episode, assessment of response to treatment, and total annualised rFIXFc consumption for prevention and treatment of bleeding episodes. All patients underwent sequential pharmacokinetic evaluations of their prestudy FIX and rFIXFc. The completed trial is registered with ClinicalTrials.gov, number NCT01440946. RESULTS No patients developed inhibitors to rFIXFc; in the 30 enrolled patients the most common adverse events were nasopharyngitis (n=7; 23%) and fall (n=6; 20%); four patients (13%) had serious adverse events. Overall, rFIXFc exhibited a prolonged half-life of 68·6 h (95% CI 61·8-76·0), reduced clearance, and similar recovery compared with prestudy FIX. The median ABR was 2·0 (0·0-3·1) overall and 0·0 (0·0-0·0) for spontaneous joint bleeds; ten (33%) of 30 patients reported no bleeding, and 19 (63%) reported no joint bleeding on-study. The median average prophylactic dose of rFIXFc was 58·6 IU/kg (IQR 52·3-64·8) per week. Throughout the study, 29 (97%) of 30 patients remained on once per week infusions. CONCLUSIONS Weekly infusions of rFIXFc were well tolerated and resulted in low bleeding rates in children with severe haemophilia B. BACKGROUND Biogen, Sobi.

UI MeSH Term Description Entries
D007141 Immunoglobulin Fc Fragments Crystallizable fragments composed of the carboxy-terminal halves of both IMMUNOGLOBULIN HEAVY CHAINS linked to each other by disulfide bonds. Fc fragments contain the carboxy-terminal parts of the heavy chain constant regions that are responsible for the effector functions of an immunoglobulin (COMPLEMENT fixation, binding to the cell membrane via FC RECEPTORS, and placental transport). This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN. Fc Fragment,Fc Fragments,Fc Immunoglobulin,Fc Immunoglobulins,Ig Fc Fragments,Immunoglobulin Fc Fragment,Immunoglobulins, Fc,Immunoglobulins, Fc Fragment,Fc Fragment Immunoglobulins,Fc Fragment, Immunoglobulin,Fc Fragments, Ig,Fc Fragments, Immunoglobulin,Fragment Immunoglobulins, Fc,Fragment, Fc,Fragments, Ig Fc,Immunoglobulin, Fc
D008297 Male Males
D011993 Recombinant Fusion Proteins Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes. Fusion Proteins, Recombinant,Recombinant Chimeric Protein,Recombinant Fusion Protein,Recombinant Hybrid Protein,Chimeric Proteins, Recombinant,Hybrid Proteins, Recombinant,Recombinant Chimeric Proteins,Recombinant Hybrid Proteins,Chimeric Protein, Recombinant,Fusion Protein, Recombinant,Hybrid Protein, Recombinant,Protein, Recombinant Chimeric,Protein, Recombinant Fusion,Protein, Recombinant Hybrid,Proteins, Recombinant Chimeric,Proteins, Recombinant Fusion,Proteins, Recombinant Hybrid
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D002836 Hemophilia B A deficiency of blood coagulation factor IX inherited as an X-linked disorder. (Also known as Christmas Disease, after the first patient studied in detail, not the holy day.) Historical and clinical features resemble those in classic hemophilia (HEMOPHILIA A), but patients present with fewer symptoms. Severity of bleeding is usually similar in members of a single family. Many patients are asymptomatic until the hemostatic system is stressed by surgery or trauma. Treatment is similar to that for hemophilia A. (From Cecil Textbook of Medicine, 19th ed, p1008) Christmas Disease,Factor IX Deficiency,Deficiency, Factor IX,F9 Deficiency,Haemophilia B,Hemophilia B Leyden,Hemophilia B(M),Plasma Thromboplastin Component Deficiency,Bs, Hemophilia,Deficiencies, F9,Deficiencies, Factor IX,Deficiency, F9,Disease, Christmas,F9 Deficiencies,Factor IX Deficiencies,Haemophilia Bs,Hemophilia Bs,Hemophilia Bs (M)
D005164 Factor IX Storage-stable blood coagulation factor acting in the intrinsic pathway of blood coagulation. Its activated form, IXa, forms a complex with factor VIII and calcium on platelet factor 3 to activate factor X to Xa. Deficiency of factor IX results in HEMOPHILIA B (Christmas Disease). Autoprothrombin II,Christmas Factor,Coagulation Factor IX,Plasma Thromboplastin Component,Blood Coagulation Factor IX,Factor 9,Factor IX Complex,Factor IX Fraction,Factor Nine,Factor IX, Coagulation
D006395 Hemarthrosis Bleeding into the joints. It may arise from trauma or spontaneously in patients with hemophilia. Hemarthroses
D006470 Hemorrhage Bleeding or escape of blood from a vessel. Bleeding,Hemorrhages
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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