Clinical Trials

Hansa Medical is currently running clinical trials with IdeS in HLA-sensitized kidney transplant patients. Full details of these clinical trials are available through a central database. Visit clinicaltrials.gov for trial information on IdeS.

If you are interested in getting involved in a clinical trial, please talk to your physician. They will be able to advise you on whether you would be eligible to enroll into a trial and if participation could be right for you.

Phase I study (Completed)

During 2013 and 2014, Hansa Medical conducted a clinical first-in-human Phase I study. The study was a randomized placebo controlled dose-escalation study with 29 (20 active plus 9 placebo) healthy subjects. The objectives were to assess safety, efficacy in IgG cleavage, pharmacokinetics and immunogenicity of IdeS following intravenous administration. The starting dose was 0.01 mg/kg BW and the highest dose group received 0.24 mg/kg BW. IdeS was considered safe and it effectively degraded the plasma IgG. In July 2015, the results from the Phase I study was published in PLOS ONE.

Based on the data from this study, it was decided to move from healthy subjects into patients where it is possible to measure not only IdeS effect on plasma IgG but also the effect on specific pathogenic IgG. The Phase I data suggested that IdeS could prove to be a therapeutic option in several clinical conditions.

First clinical Phase II in transplantation (Completed)

During 2014 and 2015, the first clinical Phase II study with IdeS treatment in sensitized patients was conducted and completed.

The study was a dose-finding study, and the intention was not to transplant patients by means of IdeS treatment. There were eight dialysis patients, ranging from very highly and broadly immunized to more moderately immunized, included in the study. One group of patients was given 0.12 mg/kg BW and one group received 0.25 mg/kg BW IdeS, and the patients were followed for two months after treatment.

The effect was measured as level of HLA antibodies, cytotoxic cross-match reactivity against hypothetical donors and level of IgG in serum/blood at different time-points after IdeS treatment. Taken into account the efficacy of the drug and the medical need for a treatment of sensitized patients, we conclude that the risk-benefit favors IdeS for desensitization prior to transplantation.

The patients participating in this trial were not intended for trans­plantation under the study protocol. However, the patients were not removed from the waiting list, and the second patient in the study was transplanted with an incompatible kidney just after completing IdeS treatment. Before IdeS treatment the cross match between donor and recipient was positive, but after treatment it was turned negative and the patient was eligible for transplantation. Stable graft function has been maintained for more than one year with normal creatinine and no rejection episodes.

Data strongly support further development in sensitized patients.

Study to Evaluate the Safety, Tolerability, Efficacy and PK of IdeS in Kidney Transplantation (Completed)

Phase II in Sweden (Completed)

In July 2015, a Phase II study in sensitized patients was initiated in Sweden and in December 2016 the study was successfully completed. The study has included ten sensitized patients on the waiting list for transplantation and the study allowed dose escalation. The objectives was to investigate both effect on HLA-antibodies and the safety of IdeS in the transplantation setting. The patients have received a single dose of IdeS which have enabled kidney transplantation i all patients. Each patient has been followed for six months. The primary and secondary objectives were met with IdeS in the study.

 

IdeS in Highly Sensitized Patients Awaiting Kidney Transplantation (Ongoing)

Investigator sponsored Phase I/II in Los Angeles

In August 2015, an investigator sponsored study using IdeS was initiated and run by Professor Stanley Jordan at Cedars-Sinai Medical Center in Los Angeles. Professor Jordan has developed a desensitization protocol that allows transplantation of highly sensitized patients using kidneys from deceased donors, a procedure that is very difficult using other protocols based on plasmapheresis. The protocol is based on the use of alternating high dose intravenous gamma globulin and anti-CD20 treatments in order to lower the levels of anti-HLA antibodies and to prevent rebound of antibodies after incompatible transplantation. The patients are kept in the program for many months waiting for an organ offer from a deceased donor. IdeS is investigated in combination with the high dose intravenous gamma globulin and anti-CD20 procedure. The study will include 10–20 patients and the patients will be followed for six months. The objectives are to investigate both efficacy (i.e. decrease in PRA, reduction in HLA antibody levels and reduction in AMR frequency) and safety of IdeS.

Highdes - A Phase II Study to Evaluate the Efficacy of IdeS to Desensitize Transplant Patients With a Positive Crossmatch Test (Ongoing)

The Phase II study will include approximately 20 highly sensitized patients awaiting kidney transplantation. Patients included in this new study have either failed on previous attempts of desensitization or the currently available methods are considered insufficiently effective.

The study is entitled “A Phase II Study to Evaluate the Efficacy of IdeS (IgG endopeptidase) to Desensitize Transplant Patients with a Positive Crossmatch Test” with the short name Highdes. The primary objective of the study is to assess the efficacy of IdeS in creating a negative crossmatch test in highly sensitized patients with a positive crossmatch test to their available donor. Converting the crossmatch test will enable transplantation in patients who would otherwise not qualify for transplantation.

The study also evaluates safety, kidney function and immunogenicity during the 6-month follow-up period. The aim is to complete recruitment of approximately 20 patients over a 12-month period. The Highdes-study was initiated in October 2016.

It is expected that the study will provide pivotal data for filing a Biologics License Application, i.e. an application to the US Food and Drug Administration (FDA) for authorization to commercialize IdeS in the US. Three US sites will recruit patients to the Highdes study: Cedars-Sinai Medical Center in Los Angeles, The Johns Hopkins Hospital in Baltimore and New York University School of Medicine in New York. Hansa Medical is planning to add European sites to the study in order to support the regulatory process at the European Medicines Agency, EMA, for marketing authorization of IdeS in the European market.

Treatment of severe AMR (Planned)

The primary aim of current AMR treatment is to remove the existing donor specific antibodies. In severe AMR plasmapheresis is not sufficient to rescue the kidney since the magnitude of the antibody response exceeds the capacity of plasmapheresis to clear anti­bodies. The completed Phase I and II studies demonstrated that IdeS cleaves and inactivates IgG very rapidly and effectively with no reflux of IgG from the tissues. This makes IdeS very interesting to investigate as a treatment for AMR and particularly severe AMR. The high-risk patients for severe AMR are those that have been desensitized and transplanted with an incompatible kidney. We are currently investigating the possibility to conduct a clinical trial in severe AMR.

IdeS in anti-GBM antibody disease (Ongoing)

In June 2017, the first patient was treated in an investigator initiated Phase II study with IdeS in anti-GBM antibody disease

The study (ClinicalTrials.gov identifier NCT03157037) is an open label investigator initiated Phase II study in severe anti-GBM disease with Professor Mårten Segelmark at Linköping University Hospital as Sponsor/Coordinating principal investigator. Approximately 15 patients will be recruited to the study at up to 15 clinics in Europe.