A possible new treatment for transplant associated microangiopathy

  • Research type

    Research Study

  • Full title

    A randomized, open label, controlled, multiple dose study to evaluate the clinical efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of LFG316 in patients with transplant associated microangiopathy after hematopoietic precursor cell transplantation.

  • IRAS ID

    219695

  • Contact name

    Andrew Gennery

  • Contact email

    a.r.gennery@ncl.ac.uk

  • Sponsor organisation

    Novartis Pharma AG

  • Eudract number

    2014-004972-49

  • Clinicaltrials.gov Identifier

    NCT02763644

  • Duration of Study in the UK

    1 years, 10 months, 27 days

  • Research summary

    Transplant associated microangiopathy (TAM) is a complication of allogeneic (from a donor) hematopoietic stem cell transplantation (HSCT).

    TAM appears to be triggered (started) by damage to cells (endothelial cells) which make up the lining of blood vessels throughout the body. TAM can lead to dysfunction of the kidneys, the digestive system and brain depending on where endothelial cells are damaged.

    The exact sequence of events that lead to TAM is poorly understood, but is thought to involve activation of components of the body’s immune system (called the complement system). Preliminary clinical data has indicated that in subjects undergoing HSCT procedures administering eculizumab has lead to a beneficial response. Eculizumab is a monoclonal antibody that blocks the activation of the compliment system by binding to complement factor 5 (C5). The study drug being evaluated in this study (LFG316) is an antibody (fully human monoclonal IgG) that also blocks the activation of the compliment system by binding to complement factor 5 (C5).

    Currently, in the UK there is no approved treatment for TAM which is associated with high morbidity and according to some estimates an associated mortality rate as high as 80%.

    The purpose of this study is to determine if LFG316 given to adults and children on top of standard of care is safe and effective in treating TAM when compared to standard of care alone.

    Subjects with TAM will enter this study which consists of 3 parts that will run in the following order. A screening/baseline period (up to 28 days), a treatment period (between 16 to 45 weeks) and a post treatment follow up period (between 7 and 26 weeks). The expected duration for any subject entering the study will be 1 year.

    Eligible subjects will be randomized to receive either standard of care plus LFG316 or standard of care alone. LFG316 will be administered via intravenous infusion once a week for 16 weeks but up to a maximum of 45 weeks. Subjects with TAM will take part in the study at hospital sites the UK.

    The study results will be used to make decisions on future clinical development of LFG316.

  • REC name

    North East - Newcastle & North Tyneside 1 Research Ethics Committee

  • REC reference

    17/NE/0004

  • Date of REC Opinion

    2 Mar 2017

  • REC opinion

    Further Information Favourable Opinion