Study of BEGEDINA® vs "Conventional Treatment" for Treating Steroid-Resistant Acute GvHD

Stopped early · Phase 3

Conditions studied: Graft vs Host Disease

In brief

The objectives of this study are to determine the efficacy and safety of BEGEDINA® in subjects with steroid resistant acute graft versus host disease (GvHD). GvHD is a rare and complex immunological disease occurring in some recipients of allogeneic hematopoietic stem cell transplants (HSCTs) and affecting principally the skin, liver and gastrointestinal (GI) tissues. The disease is life threatening and may be acute or chronic and the first choice treatment for patients with acute GvHD (Grade II or higher) is the immunosuppressive corticosteroid hormone methylprednisolone. However, some GvHD patients may be resistant to this treatment leading to disease progression and a high rate of morbidity and mortality, primarily from infections and/or multi-organ failure. There are currently no other satisfactory therapies. BEGEDINA® is a therapeutic monoclonal antibody that recognises and binds to CD26 on CD4+ T lymphocytes. BEGEDINA® reduces the activity of CD26 in these cells and inhibits the immune response leading to improvement in patients that have shown steroid resistance. This study is therefore aimed at demonstrating that BEGEDINA® is a safe and effective treatment for steroid-resistant GvHD patients where no other such treatments are currently available.

Key facts

Study ID

NCT02411084

Run by

Adienne SA

People needed

36

Starts

2016-02-01

Expected to finish

2017-07-31

Last updated by the study team

2020-01-30

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age ≥18 and ≤65 years of age.
• Recipient of an allogeneic hematopoietic stem cell transplantation (HSCT). Note: Subjects with GvHD following donor lymphocyte infusion post-HSCT are also eligible
• Steroid-resistant acute GvHD, Grade II-IV, defined as: progressive disease (deterioration of at least 1 stage in 1 organ) after 3 days of primary treatment with methylprednisolone 2 mg/kg, or equivalent. or lack of at least a partial response (PR) after 7 days of primary treatment with methylprednisolone 2 mg/kg or equivalent. or lack of a complete response (CR) after 14 days of primary treatment with methylprednisolone 2 mg/kg or equivalent. Note: Subjects who may have received an increase in their steroid dose treatment prior to randomization will be eligible for enrollment. An increase in steroid dose will not be considered as second-line therapy.
• Evidence of previous myeloid engraftment (absolute neutrophil count ≥0.5 x 10\^9/L).
• Karnofsky Performance Status Scale ≥50%.
• Adequate renal function as defined by serum creatinine ≤2 × upper limit of normal or calculated creatinine clearance (CrCl) of ≥30 mL/min using the Cockroft-Gault equation: Calculated CrCl= ([140-age in years] x [ideal body mass {IBM} in kg])/72 x (serum creatinine value in mg/dL), where IBM = IBM (kg) = ([height in cm- 154] × 0.9) + (50 if male, 45.5 if female).
• Subject must be willing and able to comply with study requirements, remain at the clinic, and return to the clinic for the follow-up evaluation, as specified in this protocol during the study period.
• Able and willing to provide signed informed consent.

You may not qualify if…

• Subjects will not be entered in the study for any of the following reasons:
• Prior second-line systemic treatment for GvHD.
• Received agents other than steroids for primary treatment of acute GvHD.
• Stage 1-2 skin acute GvHD alone (with no other organ involvement).
• Acute steroid resistant GvHD beyond 28 days from first-line therapy (primary treatment).
• Evidence of severe hepatic veno-occlusive disease or sinusoidal obstruction.
• Evidence of encephalopathy.
• Life expectancy <3 weeks.
• Presence of chronic GvHD
• Second or subsequent allogeneic transplant.
• Previous solid organ transplant (with the exception of a corneal transplant >3 months prior to screening).
• Relapsed disease after last transplant.
• Human immunodeficiency virus positive.
• Evidence of lung disease that is likely to require more than 2 liter per minute of O2 via face mask or an estimated FiO2 of 28% via other delivery methods in order to sustain an O2 saturation of 92% within the next 3 days.
• Any underlying or current medical or psychiatric condition that, in the opinion of the investigator, would interfere with the evaluation of the subject including uncontrolled infection, heart failure, pulmonary hypertension. Any other serious medical condition, as judged by the investigator, which places the subject at an unacceptable risk if he or she were to participate in the study or confounds the ability to interpret data from the study.
• Administration of any other investigational agents (not approved by the United States Food and Drug Agency [FDA] or European Medicines Agency [EMA] for any indication) within 30 days of randomization. Participated in any interventional clinical trial for an acute GvHD therapeutic agent or for an immunomodulatory drug, within the past 30 days or within 5 half-lives of the study treatment, whichever is the greater. Participated or is currently participating in any bone marrow derived autologous and allogeneic stem cell or gene therapy study.
• Known hypersensitivity to murine proteins.
• Women who are pregnant, breastfeeding or at risk to become pregnant during study participation; female subjects of childbearing potential who have not been started on an anti-ovulatory regimen prior to initiation of chemo-inductive regimen must test negative for pregnancy (serum) at the time of enrollment.
• Male and female subjects who do not agree to take adequate measures to avoid pregnancy prior to study entry and for the duration of participation in the study (or for at least 3 months following the last dose of study drug, whichever is longer) (acceptable methods of birth control are described in protocol Section 6.2.1.6).

Where it is running

• City of Hope Comprehensive Cancer Center — Duarte, California, United States
• University of Kansas Cancer Center and Medical Pavilion — Westwood, Kansas, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• Washington University School of Medicine — St Louis, Missouri, United States
• Hackensack University Medical Center - John Theurer Cancer Center — Hackensack, New Jersey, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• Duke Cancer Center — Durham, North Carolina, United States
• The Ohio State University — Columbus, Ohio, United States
• Oregon Health & Science University — Portland, Oregon, United States
• Huntsman Cancer Center, University of Utah — Salt Lake City, Utah, United States
• Centre Hospitalier Universitaire de Grenoble — La Tronche, France
• Hospital Saint-Louis APHP (Hôpitaux Universitaires Sant-Louis) — Paris, France
• Centre Hospitalier Lyon-Sud — Pierre-Bénite, France
• Universitätsklinikum Hamburg-Eppendorf — Hamburg, Germany
• Ospedale Casa Sollievo della Sofferenza, IRCCS — San Giovanni Rotondo, Foggia, Italy
• Policlinico S.Orsola Malpighi, AOU di Bologna — Bologna, Italy
• L'IRCCS A.O.U. San Martino - IST — Genova, Italy
• Ospedale San Raffaele — Milan, Italy
• A.O. Universitaria Policlinico Tor Vergata — Roma, Italy
• Policlinico Universitario Agostino Gemelli — Roma, Italy
• Ospedale Molinette — Torino, Italy
• Hospital Universitari Vall d'Hebron — Barcelona, Spain
• Hospital de la Santa Creu i Sant Pau — Barcelona, Spain
• Hospital Univeristario de Salamanca — Salamanca, Spain
• Hospital Universitari Politecnic La Fe — Valencia, Spain

Full record on ClinicalTrials.gov

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