Nephrologist Prof. Lutz Renders (Klinikum Rechts der Isar, Germany) explained that patients with chronic kidney disease (CKD) commonly present with anaemia. Current treatment regimens consist of iron, erythropoietin stimulating agents (ESAs), or both, but a significant proportion of patients remain anaemic despite these therapies. Hepcidin, a liver-derived hormone, is a central regulator of iron homeostasis, frequently elevated in CKD patients and thought to represent a root cause of hypoferremia. Therefore, hepcidin inhibition has the potential to ameliorate functional iron deficiency anaemia in CKD patients. PRS-080 is a pegylated hepcidin protein antagonist that has been shown to induce dose-dependent serum iron mobilisation and increased transferrin saturation (TSAT) in single ascending dose phase 1 clinical studies, both in healthy male volunteers and dialysis-dependent CKD patients [2].
The study authors aimed to determine the safety and tolerability of 5 repeated intravenous administrations of PRS-080 at doses of 4 and 8 mg/kg body weight compared with placebo in anaemic, haemodialysis-dependent stage 5 CKD patients, as well as to assess pharmacokinetics, pharmacodynamics, and immunogenicity. The decision to escalate the dose was based on an interim analysis of clinical and laboratory safety as well as on a comparison with pharmacokinetic data.
Twelve patients were enrolled. Using a standard 4+2 design, 4 patients in each cohort were randomised to PRS-080, and 2 patients to placebo. The study included a screening period of 4 weeks; the mean of 3 Hb values during the screening period, each obtained at least 7 days apart, was required to be ≤10.5 g/dL with a difference of ≤1.0 g/dL between the lowest and highest values. Additional inclusion criteria included ferritin > 300 ng/mL and TSAT ≤30%. The ESA dose had to remain stable for at least 4 weeks prior to screening, as well as through the treatment period, and iron therapy had to be withdrawn 1 week before randomisation. Study medication was administered by infusion over 60 minutes using an infusion pump on day 0, 7, 14, 21, and 28. Patients were observed with regard to safety up until day 112. Safety was monitored continuously by a data safety monitoring board, including prior to dose escalation.
The study results indicated no treatment-related adverse events or serious adverse events. Robust iron mobilisation with increases in both serum iron and TSAT were consistently observed following each weekly dose in both dose cohorts. Peak iron concentrations were higher in the 8 mg/kg cohort than in the 4 mg/kg cohort.
Whereas no clear difference was observed in Hb values between placebo and PRS-080 patients in the 4 mg/kg cohort over the course of treatment, evidence of a Hb response with clear separation of Hb values between placebo and PRS-080 could be shown in the 8 mg/kg cohort during the treatment period, consisting of an increase of Hb in drug-treated patients and a decline in placebo patients, potentially related to the withdrawal of iron treatment.
- Renders L, et al. Abstract S1630, 24th Congress of the EHA, 13-16 June 2019, Amsterdam, the Netherlands.
- Renders L, et al. PLoS One. 2019 Mar 27;14(3):e0212023.
Posted on
Previous Article
« Subcutaneous daratumumab + cyclophosphamide, bortezomib, and dexamethasone in patients with newly diagnosed amyloid light chain amyloidosis Next Article
Infectious complications mild and not common in patients receiving CAR-T therapy for diffuse large B cell lymphoma »
« Subcutaneous daratumumab + cyclophosphamide, bortezomib, and dexamethasone in patients with newly diagnosed amyloid light chain amyloidosis Next Article
Infectious complications mild and not common in patients receiving CAR-T therapy for diffuse large B cell lymphoma »
Table of Contents: EHA 2019
Featured articles
Editor Biography
Interview with EHA President Prof. Pieter Sonneveld
Myeloid Malignancies
Residual disease in AML patients prior to stem cell transplant increases relapse risk
Gilteritinib prolongs overall survival in patients with FLT3-mutated relapsed/refractory AML
Initial data on AMV564 in patients with relapsed/refractory AML
Overcoming the “don’t eat me” signal in AML and MDS
Asciminib plus imatinib in patients with heavily pre-treated chronic myeloid leukaemia
Guadecitabine vs treatment of choice in AML
Lymphoid Malignancies
Unmutated IGHV as predictive factor for venetoclax/obinutuzumab benefit in frontline CLL
CAR-T cell therapy in ALL as breakthrough advance
Brentuximab vedotin continues to demonstrate superior clinical activity in classical Hodgkin lymphoma
Infectious complications mild and not common in patients receiving CAR-T therapy for diffuse large B cell lymphoma
Obinutuzumab/polatuzumab in follicular lymphoma
Exciting survival data for ibrutinib vs placebo in treatment-naĂŻve, early-stage CLL
ASCEND study: Acalabrutinib improves progression-free survival in relapsed/refractory CLL
Venetoclax-obinutuzumab combination elicits high response rates in CLL
Myeloma
CASSIOPEIA trial: Phase 3 results of daratumumab + bortezomib/thalidomide/dexamethasone in multiple myeloma
Chimeric antigen receptor T cell therapy in multiple myeloma
Higher levels of treatment satisfaction without compromising efficacy: subcutaneous daratumumab in RRMM
Adding isatuximab to pomalidomide and dexamethasone improves PFS and ORR in RRMM
Subcutaneous daratumumab + cyclophosphamide, bortezomib, and dexamethasone in patients with newly diagnosed amyloid light chain amyloidosis
Venetoclax for multiple myeloma: effective but some safety concerns
Benign Haematology
New sickle cell drug voxelotor boosts levels of haemoglobin
Positive initial data evaluating the safety and efficacy of IMR-687 for treatment of sickle cell disease
Haematopoietic stem cell transplantation improves stroke risk in children with sickle cell anaemia
Early trial data shows positive results for treating anaemia in patients with end-stage renal failure
Bench-to-Bedside
Transformation of foetal haematopoietic stem and progenitor cells in the background of trisomy 21
Treating thalassemia twice, in mice
Haematopoietic stem cells can sense tissue damage in the gut
Promising news for gene therapy for sickle cell disease
Related Articles
August 9, 2019
Introduction to the Conference Report of the EHA
© 2024 Medicom Medical Publishers. All rights reserved. Terms and Conditions | Privacy Policy