The HIPGEN project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement n. 779293
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The HIPGEN project aims at bringing the first regenerative therapy for improving recovery following a surgically treated injury to market approval. The major focus of the HIPGEN are patients undergoing to total or hemiarthoplasty after hip fracture (→ less).
Hip fractures of the femoral neck are a major public health concern in the EU with an increasing incidence of 1 million patients per year, high direct and indirect costs due to the resulting immobility after fracture and surgery, and a mortality comparing to cancer with up to 30% during the first year. The elderly patients are massively challenged by the incidence of injury and the consecutive surgery and exhibit a very low regenerative capacity. No therapy is currently available to address the problem of impaired regeneration and mobility and the consequences, including the high mortality, after hip fracture surgery.
Picture from the National Library of Medicine nlm.nih.gov
• ALL patients are surgically treated
• Europe: hemiarthroplasty (HA): internal fixation (IF) 50:50
• USA: more HA than IF
• Data show high revision rate in IF cases due to non-union
Problem of surgical interventions: Intraoperative muscle trauma on top of damage-predisposing sarcopenia in elderly patients → impaired mobilization + surgical stress in frail patients → high mortality.
Picture from Sein letztes Rennen, BR, Universum Film GmbH 2013
Therapy Cell product: PLX-PAD
We will conduct a multicentre phase III clinical study assessing the improvement of restoring muscle function, mobility and the reduction of post-operative stress-related immune disbalance in hip fracture patients treated with placenta-expanded adherent stromal cells (PLX-PAD cells → more) after arthroplasty.
By these regenerative mechanisms, we also aim at improving the survival of these patients.
Within the study we will confirm the safety and promising efficacy phase I/II data from patients undergoing total hip arthroplasty, and we enhance our understanding on the mode-of-action (MoA) of PLX-PAD.
HIPGEN partners are world-leading experts in orthopaedic surgery or rehabilitation, clinical immunology and performing innovative clinical studies, 3D-cell manufacturing , preclinical and clinical cell therapy and biomarker analyses.
Which city would be a better place to arrange a final Meeting for the European Union-funded project "HipGen" than Brussels?
Since there is none, the final HipGen meeting took place in the artsiest, most impressive, and most elaborate building with a beautiful panorama over Brussels and an ounce of scientific reference and spice: The Atomium.
Last Patient in - Important Milestone reached
Topline results will be available in the third calendar quarter of 2022.
Reaching our enrollment target for the Phase III PLX-PAD study is an important milestone.
Rising healthcare costs and aging demographic changes present an opportunity for allogenic, placenta-cell derived products to satisfy unmet clinical needs in the area of muscle regeneration following hip arthroplasty. The potential improvement of physical function following this common procedure could redefine the current standard of care and improve patients' lives.
HIPGEN Phase III clinical trial at the Virtual WCO-IOF-ESCEO 2021
The year’s key annual congress in the bone and musculoskeletal field will present a satellite symposium dedicated to the HIPGEN clinical trial, a multinational study which aims to improve patient mobility after hip fracture arthroplasty
→ HIPGEN PRESS RELEASES & MAGAZINE ARTICLES
Report on the Second Annual HIPGEN Meeting in Berlin.
More on → International Osteoporosis Foundation Newsletter
HIPGEN participates to RESTORE 1ATSM in Berlin
In the programme:
● Tobias Winkler, Project coordinator presents HIPGEN study
● Racheli Ofir, Pluristem gives a talk about development of allogeneic Placenta-derived (PLX) cell therapy
● Posters presented by Marta Magatti and Antonietta Silini Centro di Ricerca E. Menni, Fondazione Poliambulanza - Istituto Ospedaliero (CREM)
HIPGEN presented at RegMed Forum 2019 in Berlin
More on → International Osteoporosis Foundation Newsletter
HIPGEN Updates after 18 Months
More on → PROJECT STATUS
Tobias Winkler, HIPGEN project coordinator, discusses the background and aims of the innovative project. In the three VIDEOS he explains:
More on → COMMUNICATION
HIPGEN participates to WORLD CONGRESS ON OSTEOPOROSIS, OSTEOARTHRITIS AND MUSCULOSKELETAL DISEASES in Paris (France)
More on → WCO-IOF-ESCEO Paris 2019
15 open sites from 4 countries
Human placenta stem cells help people recover from hip surgery
More on → NewScientist - NEWS & TECHNOLOGY
HIPGEN first patient-in
HIPGEN website online
U.S. Food and Drug Administration (FDA) has cleared Pluristem’s Investigational Drug Application (IND) of its PLX-PAD cell therapy for HIPGEN study
More on → PRESS RELEASES & MAGAZINE ARTICLES
Hip fractures are defined as fractures of the proximal femur, among them neck of femur fractures and per- or subtrochanteric fractures, both constituting half of all hip fractures. In Europe, roughly 50% of all neck of femur fractures are surgically treated with an internal fixation device, mostly gliding screws, however, this is prone to a high complication and revision rate (15% non-fusion). This is the reason why increasingly more neck of femur fractures are treated with hemi- (HA) or total arthroplasty (THA), allowing for immediate total weight bearing mobilisation, which should be life saving for these patients. Nevertheless, mortality rates of these frail patients treated with internal fixation and arthroplasty are the same. The reasons for this are damage resulting from joint exposition during arthroplasty, poor regeneration capacity, immunological stress due to the trauma and consecutive surgery Hence, the death rate of hip fracture patients is comparable to malignant diseases with a 1-year mortality rate of 25% - 30 %. As a consequence, there is a high need for the development of a new therapeutic option for these patients in order to
To date, no therapeutic option exists other than adjustments in the general set-up for the patients suffering from hip fracture, e.g. rehabilitation procedures.
We propose a new innovative therapy, which is in advanced clinical development stage: allogeneic placental cell therapy with PLX-PAD cells (→ more) for the enhanced recovery following hip fracture surgery. Within this project, we will perform a multi-center phase III clinical study with 240 patients. Internationally renowned European orthopaedic and trauma centres will be partners in the trial (University of Oxford, Odense University Hospital) and further renowned clinical centres and hospitals will be included in the trial. As a catalyst for improved patient engagement, an innovative patient platform implemented by Be the Partner will be used for the first time in an ATMP trial.
PLX-PAD, an allogeneic cell-based dispersion for injection and classified as an Advanced Therapy Medicinal Product (ATMP), is comprised of ex-vivo expanded placental adherent stromal cells that are derived from human placentae. The placentae are collected from healthy women undergoing elective Caesarean section. The placenta donors sign an informed consent form and are not compensated for this donation. No ethical issues are known to exist in the use of placenta derived stromal cells.
PLX-PAD cells are manufactured, packaged and labelled by Pluristem Ltd. in GMP-compliant facilities located in Haifa, Israel. The PLX-PAD cell expansion manufacturing process consists of two stages.
Schematic manufacturing process for the two major PLX products.
The first stage consists of isolating the adherent stromal cells from a placenta and the expansion of these cells by 2-dimensional growth to produce the intermediate cell stock. During the second stage, the intermediate cell stock is thawed and undergoes further culture expansion using 2- and 3- dimensional growth to produce the PLX-PAD drug substance. PLX-PAD cells have a population doubling level limited to no more than 25 from the original extraction of placental cells until cryopreservation of the final cell product. If passaged in vitro, the final PLX-PAD cells reach senescence within ~37 additional population doublings while maintaining a stable karyotype.
PLX-PAD cells are provided as a frozen cell dispersion in cryogenic vials containing 6 mL, at a cell concentration of either 10 million cells/mL or 20 million cells/mL in a solution containing 10% (v/v) dimethyl sulfoxide (DMSO), 5% (w/v) human serum albumin (HSA) in Plasma-Lyte A. PLX-PAD is stored in the vapor phase of liquid nitrogen below -150°C. The shelf life of the product is currently 36 months and ongoing stability studies aim to allow its’ extension.
It is essential to underline that the production process is industrially scalable and already EMA and FDA approved.
A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study, Designed to Determine the Efficacy, Safety and Tolerability of Intramuscular Injections of Allogeneic PLX-PAD Cells improved recovery following Arthroplasty for Hip Fracture (HF).
Protocol Number: PLX-HF-01 Investigational Treatment: Allogeneic ex-vivo expanded placental stromal cells (PLX-PAD).
The Network consists of 10 partners from 8 Countries (Germany, Denmark, UK, Ireland, Italy, Switzerland, Israel and United States).
The clinical and research centers in the Consortium have a renowned international expertise on hip fracture arthroplasty and cell therapy respectively while Pluristem is a lead company in the cell therapy development. All the Partners have been selected for their excellence in the field.
The HIPGEN consortium includes also the Irish CRO ICON that will manage the multicentre clinical trial, the company Be the Partner that has developed the platform for patient data management and the service provider company INN-ACTA that will support the consortium in the coordination, dissemination and exploitation, allowing the scientists to focus on the science and the business developer on business. Finally, the International Osteoporosis foundation gives an added value of the consortium by filling the communication gap between science and patients.
The high degree of synergy among our participants ensures that the program will be successful and that their combined output will be greater than the sum of its parts. The European dimension of the project is an added value of the proposal, in terms of achieving the necessary critical mass (regarding patient enrollment, clinical infrastructures, availability of samples for analysis), financial support and good visibility.
Final HIPGEN Annual Meeting, 12-13 September 2022 in Brussels
Atomium Pl. de l’Atomium 1 1020
HIPGEN Fourth Annual Meeting, 1 March 2022
HIPGEN Third Annual Meeting, 2 March 2021
HIPGEN Second Annual Meeting, 3-4 March 2020 in Berlin
Steigenberger Hotel Am Kanzleramt
HIPGEN First Annual Meeting, 19-21 February 2019
Siena - Confindustria Toscana Sud
HIPGEN KICK OFF MEETING, 14-16 January 2018
Berlin - BCRT Charité
What previous work is the HIPGEN project based on
What are the goals of the HIPGEN project
How the HIPGEN project is going to improve patients quality of life
HIPGEN leaflet - February 2019 version
December 27, 2021 - Important milestone for HIPGEN as it reaches enrolment target
March 30, 2021 - HIPGEN Third annual meeting (virtual)
March 30, 2020 - Report on the Second Annual HIPGEN Meeting in Berlin
October 28, 2019 - HIPGEN presented at RegMed Forum 2019 in Berlin
March 14, 2019 - First Annual HIPGEN Meeting reviews current progress and challenges
June 15, 2019 - "Long Night of Sciences", Berlin, Germany
June 26, 2018 - "Long Night of Sciences", Berlin, Germany