Graft vs Host DiseasePhase 3NCT02411084
Study of BEGEDINA® vs "Conventional Treatment" for Treating Steroid-Resistant Acute GvHD
A Phase 3 study testing Begelomab and Conventional Second-line Treatment in people with Graft vs Host Disease, run by Adienne SA at 27 sites in 7 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Graft vs Host Disease
- What is being tested?
- Begelomab and Conventional Second-line Treatment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 27 sitesin 7 countries
- Study dates
- Feb 2016to 31 Jul 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 19Show fewer
- 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).
Trial locations and contacts
27 sites in 7 countries.
27 sites in 7 countries
United States10 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
The Ohio State University
Columbus, Ohio, 43210
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Duke Cancer Center
Durham, North Carolina, 27710
Hackensack University Medical Center - John Theurer Cancer Center
Hackensack, New Jersey, 07601
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Oregon Health & Science University
Portland, Oregon, 97239
Huntsman Cancer Center, University of Utah
Salt Lake City, Utah, 84112
Washington University School of Medicine
St Louis, Missouri, 63110
University of Kansas Cancer Center and Medical Pavilion
Westwood, Kansas, 66205
Italy7 sites
Policlinico S.Orsola Malpighi, AOU di Bologna
Bologna, 40138
L'IRCCS A.O.U. San Martino - IST
Genova, 16132
Ospedale San Raffaele
Milan, 20132
A.O. Universitaria Policlinico Tor Vergata
Roma, 00133
Policlinico Universitario Agostino Gemelli
Roma, 00168
Ospedale Casa Sollievo della Sofferenza, IRCCS
San Giovanni Rotondo, Foggia, 71013
Ospedale Molinette
Torino, 10126
Spain4 sites
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital de la Santa Creu i Sant Pau
Barcelona, 08041
Hospital Univeristario de Salamanca
Salamanca, 37007
Hospital Universitari Politecnic La Fe
Valencia, 46026
France3 sites
Centre Hospitalier Universitaire de Grenoble
La Tronche, 38700
Hospital Saint-Louis APHP (Hôpitaux Universitaires Sant-Louis)
Paris, 7545
Centre Hospitalier Lyon-Sud
Pierre-Bénite, 69310
United Kingdom1 site
University Hospital Southampton NHS Foundation Trust
Southampton, SO16 6YD
About this study
Official title: Prospective, Phase II/III, Randomized Clinical Study to Compare BEGEDINA® Versus "Conventional Treatment" for Treating Steroid Resistant Acute Graft-versus Host Disease
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.
Read the detailed description
This is a prospective, phase II/III, randomized clinical study to compare the efficacy and safety of BEGEDINA® (Begelomab) versus "conventional treatment" for treating steroid-resistant acute graft versus host disease (GvHD). Despite prophylactic treatment, GvHD still develops in up to 30% of allogeneic hemopoietic stem cell transplant (HSCT) recipients. GvHD is a life-threatening and complex immunological disease that may be acute or chronic. Acute GvHD affects mainly the skin, liver and gastrointestinal (GI) tissues with long-term survival directly related to the severity of skin, liver and gut involvement. First line treatment for patients with acute GvHD (Grade II or higher) is the immunosuppressive corticosteroid methylprednisolone. Although effective in over 50% of patients, durable responses are observed in only a third of patients and it also confers a risk of severe infection. Steroid-resistant acute GvHD is associated with a high rate of morbidity and mortality, primarily from infections and/or multi-organ failure. Despite this, there are no authorized treatments for non-responders and GvHD remains largely an untreatable disease with limited survival and thus a great unmet therapeutic need. BEGEDINA® (Begelomab) is a murine immunoglobulin G (IgG) 2b monoclonal antibody against CD26 (dipeptidyl peptidase-4; DPP4) and is produced by biotechnological means and is a new potential therapeutic approach. BEGEDINA® has been shown to bind to CD26 which is present on a subset of CD4+ T helper lymphocytes leading to down-regulation of CD26 signaling and inhibition of immune response and thus therapeutic improvements. BEGEDINA has been investigated in two completed clinical studies: a pilot study and a dose-finding study and so far showing promising efficacy, safety and tolerability.
The primary objective for this study is therefore to determine the efficacy of BEGEDINA® versus conventional therapy in steroid-resistant acute GvHD. To satisfy this objective, two co primary hypothesis will be tested. The first is that the overall response rate consisting of the Complete Responders and the Partial Responders (CR+PR) at Study Day 28 will be higher in the BEGEDINA® treated subjects. The second is that the incidence of transplant-related mortality (TRM) at 6 months will be reduced in those subjects treated with BEGEDINA® versus those treated with conventional therapy. Additional secondary efficacy endpoints will also be assessed as a measure of effectiveness. In addition, some pharmacokinetics assessments will be performed. Adverse events (AEs) will be coded using MedDRA and the frequency, causality and intensity of AEs will be compared to conventional therapies. Further safety analysis will also include laboratory findings, vital signs, immunogenicity and other assessments. Finally, some exploratory analysis will also be performed.
This will be a prospective, multicenter, randomized, open-label, phase II/III clinical study in which subjects will be randomly assigned in a 1:1 ratio to receive BEGEDINA® treatment or the best conventional treatment available in their territory as no second line therapy is currently approved. It is planned to enroll 184 male or female adult subjects with an upper age limit of 65 years with steroid-resistant acute GvHD. BEGEDINA® will be administered at a dose of 2.7 mg/m2/day for 5 consecutive days from Study Day 1 through to Study Day 5, and on Study Days 10, 14, 17, 21, 24, and 28. Thus, the expected duration for each subject will be approximately 12 months. The final statistical analysis plan (SAP) will be finalized prior to database lock. Baseline characteristics of the subject sample will be described using summary statistics. All statistical tests will be conducted at a 2-sided significance level of 5% unless specifically specified. Multiple Imputation methods will be used as the primary method for accounting for missing data.
- Conditions
- Graft vs Host Disease
- Being tested
- Begelomab, Conventional Second-line Treatment
- Keywords
- Graft vs Host Disease, Immune System Diseases, Dipeptidyl Peptidase 4, CD4-Positive T-Lymphocytes, Hematopoietic Stem Cell Transplantation
- Medical subject headings
- Graft vs Host Disease, Immune System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BegelomabBiological
Also called BEGEDINA®
BEGEDINA® (Begelomab) is a murine immunoglobulin G (IgG) 2b monoclonal antibody against CD26 (dipeptidyl peptidase-4; DPP4) and is produced by biotechnological means.
Conventional Second-line TreatmentBiological
There are no approved second-line treatments for aGvHD and due to the life-threatening nature of the disease it was agreed with the FDA and EMA that BEGEDINA® would be compared with "best conventional second-line treatments" which will be chosen by each center, based on the clinical conditions of the individual subject and according to the standard practice at the study center and which may vary between centers. Treatments are generally biological products and could include anti-thymocyte globulin, monoclonal antibodies, such as anti-CD147, basiliximab, daclizumab and alemtuzumab; mycophenolate mofetil; anti-TNF-alpha; pentostatin; dinileukin diftitox; N-acetyl-cysteine; sirolimus; and visulizumab.
| Study group | Role | What they receive |
|---|---|---|
| BEGEDINA® (Begelomab) | Experimental | BEGEDINA® (Begelomab) (murine monoclonal antibody against CD26). Dose is 2.7 mg/m2/day i.v. infusion for 5 consecutive days (Study Days 1, 2, 3, 4, 5) and then single dose on each of Study Days 10, 14, 17, 21, 24 and 28, for a total of 11 doses. BEGEDINA® is supplied as 1 mg/mL concentrate for solution for infusion in vials of 6 mL (5.4 mg of active substance) for reconstitution. The total volume to be administered should be further diluted in 100 mL of 0.9% sodium chloride solution for injection prior to administration. The infusion lasts 60 minutes. Subjects are eligible for a single treatment for flare after study Day 28 Receives: Biological: Begelomab |
| Conventional Second-line Treatment | Active comparator | Subjects in the conventional treatment arm will receive a second line treatment, which is to be chosen by each center, based on the clinical conditions of the individual subject and according to the standard practice at the study center. Currently no treatments for this life-threatening disease have been approved in either the USA or Europe. The recommendations of the American Society for Blood and Marrow Transplantation (ASBMT) confirm that no treatment for acute steroid-refractory GvHD can be considered gold standard in terms of TRM or survival as results remain unsatisfactory and this approach has been agreed by the FDA and the EMA. Receives: Biological: Conventional Second-line Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Overall Response at 28 Days
The change in grade from baseline to Study Day 28 (-1/+2 day) was used to determine the response of GvHD to treatment using the following classifications:
- Complete response (CR): complete resolution of all signs of GvHD.
- Partial response (PR): improvement of 1 overall grade (i.e., change from baseline in IBMTR to a less severe grading).
- Stable disease (SD): No change in GvHD grading (i.e., no change from baseline in IBMTR grade).
- Disease progression (PD): Deterioration in one overall grade in GvHD (i.e., worsening in IBMTR by at least 1 grade compared to baseline).
- Death
Measured: 28 days for OR
Secondary outcomes (3)
Number of Participants With Overall Survival (OS) up to 180 Days
For this endpoint, no statistical confirmatory test could be performed due to insufficient sample size.
Measured: Time frame is up to 180 days
BEGEDINA Serum Concentrations Pre- and 15 Minutes Post-Infusion
The pharmacokinetic (PK) objective for this study was to characterize the serum concentrations of BEGEDINA in subjects with Grades II-IV acute GvHD who have failed to respond to steroid treatment. Data was analyzed before and 15 minutes after infusion.
Measured: Time frame is up to Day 28
Number of Participants With Adverse Events
The safety parameters were analysed at the end of the study period (Day 180).
Measured: The safety parameters were analysed at the end of the study period (Day 180)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2015 (estimated)
- Study startFeb 2016
- Primary completion31 Jul 2017
- Study completion31 Jul 2017
Why it stopped: Insufficient rate of accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Graft vs Host DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Adienne SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- ADIENNE S.r.l. S.U.
- Responsible party
- Sponsor
- Investigators
- Andrea Bacigalupo, MD, Principal investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02411084
- Sponsor's protocol ID
- ADN011
- Other IDs
- 2015-001360-19, 2015
- Status last verified
- Jan 2020
- First submitted
- 24 Mar 2015
- Last updated
- 30 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Phase II/III, Randomized Clinical Study to Compare BEGEDINA® Versus "Conventional Treatment" for Treating Steroid Resistant Acute Graft-versus Host Disease
- ClinicalTrials.gov ID
- NCT02411084
- Acronym / sponsor ID
- ADN011
- Conditions
- Graft vs Host Disease
- Keywords
- Graft vs Host Disease, Immune System Diseases, Dipeptidyl Peptidase 4, CD4-Positive T-Lymphocytes, Hematopoietic Stem Cell Transplantation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient rate of accrual
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Adienne SAIndustry (pharma, biotech, devices)
- Collaborators
- ADIENNE S.r.l. S.U.
- Study start
- Feb 2016
- Primary completion
- 31 Jul 2017 (actual)
- Study completion
- 31 Jul 2017 (actual)
- First posted
- 8 Apr 2015 (estimated)
- Results
- Posted 30 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a prospective, phase II/III, randomized clinical study to compare the efficacy and safety of BEGEDINA® (Begelomab) versus "conventional treatment" for treating steroid-resistant acute graft versus host disease (GvHD). Despite prophylactic treatment, GvHD still develops in up to 30% of allogeneic hemopoietic stem cell transplant (HSCT) recipients. GvHD is a life-threatening and complex immunological disease that may be acute or chronic. Acute GvHD affects mainly the skin, liver and gastrointestinal (GI) tissues with long-term survival directly related to the severity of skin, liver and gut involvement. First line treatment for patients with acute GvHD (Grade II or higher) is the immunosuppressive corticosteroid methylprednisolone. Although effective in over 50% of patients, durable responses are observed in only a third of patients and it also confers a risk of severe infection. Steroid-resistant acute GvHD is associated with a high rate of morbidity and mortality, primarily from infections and/or multi-organ failure. Despite this, there are no authorized treatments for non-responders and GvHD remains largely an untreatable disease with limited survival and thus a great unmet therapeutic need. BEGEDINA® (Begelomab) is a murine immunoglobulin G (IgG) 2b monoclonal antibody against CD26 (dipeptidyl peptidase-4; DPP4) and is produced by biotechnological means and is a new potential therapeutic approach. BEGEDINA® has been shown to bind to CD26 which is present on a subset of CD4+ T helper lymphocytes leading to down-regulation of CD26 signaling and inhibition of immune response and thus therapeutic improvements. BEGEDINA has been investigated in two completed clinical studies: a pilot study and a dose-finding study and so far showing promising efficacy, safety and tolerability.
The primary objective for this study is therefore to determine the efficacy of BEGEDINA® versus conventional therapy in steroid-resistant acute GvHD. To satisfy this objective, two co primary hypothesis will be tested. The first is that the overall response rate consisting of the Complete Responders and the Partial Responders (CR+PR) at Study Day 28 will be higher in the BEGEDINA® treated subjects. The second is that the incidence of transplant-related mortality (TRM) at 6 months will be reduced in those subjects treated with BEGEDINA® versus those treated with conventional therapy. Additional secondary efficacy endpoints will also be assessed as a measure of effectiveness. In addition, some pharmacokinetics assessments will be performed. Adverse events (AEs) will be coded using MedDRA and the frequency, causality and intensity of AEs will be compared to conventional therapies. Further safety analysis will also include laboratory findings, vital signs, immunogenicity and other assessments. Finally, some exploratory analysis will also be performed.
This will be a prospective, multicenter, randomized, open-label, phase II/III clinical study in which subjects will be randomly assigned in a 1:1 ratio to receive BEGEDINA® treatment or the best conventional treatment available in their territory as no second line therapy is currently approved. It is planned to enroll 184 male or female adult subjects with an upper age limit of 65 years with steroid-resistant acute GvHD. BEGEDINA® will be administered at a dose of 2.7 mg/m2/day for 5 consecutive days from Study Day 1 through to Study Day 5, and on Study Days 10, 14, 17, 21, 24, and 28. Thus, the expected duration for each subject will be approximately 12 months. The final statistical analysis plan (SAP) will be finalized prior to database lock. Baseline characteristics of the subject sample will be described using summary statistics. All statistical tests will be conducted at a 2-sided significance level of 5% unless specifically specified. Multiple Imputation methods will be used as the primary method for accounting for missing data.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BEGEDINA® (Begelomab) | Experimental | Biological: BegelomabBEGEDINA® (Begelomab) (murine monoclonal antibody against CD26). Dose is 2.7 mg/m2/day i.v. infusion for 5 consecutive days (Study Days 1, 2, 3, 4, 5) and then single dose on each of Study Days 10, 14, 17, 21, 24 and 28, for a total of 11 doses. BEGEDINA® is supplied as 1 mg/mL concentrate for solution for infusion in vials of 6 mL (5.4 mg of active substance) for reconstitution. The total volume to be administered should be further diluted in 100 mL of 0.9% sodium chloride solution for injection prior to administration. The infusion lasts 60 minutes. Subjects are eligible for a single treatment for flare after study Day 28 |
| Conventional Second-line Treatment | Active comparator | Biological: Conventional Second-line TreatmentSubjects in the conventional treatment arm will receive a second line treatment, which is to be chosen by each center, based on the clinical conditions of the individual subject and according to the standard practice at the study center. Currently no treatments for this life-threatening disease have been approved in either the USA or Europe. The recommendations of the American Society for Blood and Marrow Transplantation (ASBMT) confirm that no treatment for acute steroid-refractory GvHD can be considered gold standard in terms of TRM or survival as results remain unsatisfactory and this approach has been agreed by the FDA and the EMA. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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%.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BegelomabAlso: BEGEDINA®BEGEDINA® (Begelomab) is a murine immunoglobulin G (IgG) 2b monoclonal antibody against CD26 (dipeptidyl peptidase-4; DPP4) and is produced by biotechnological means. | Biological | BEGEDINA® (Begelomab) |
| Conventional Second-line TreatmentThere are no approved second-line treatments for aGvHD and due to the life-threatening nature of the disease it was agreed with the FDA and EMA that BEGEDINA® would be compared with "best conventional second-line treatments" which will be chosen by each center, based on the clinical conditions of the individual subject and according to the standard practice at the study center and which may vary between centers. Treatments are generally biological products and could include anti-thymocyte globulin, monoclonal antibodies, such as anti-CD147, basiliximab, daclizumab and alemtuzumab; mycophenolate mofetil; anti-TNF-alpha; pentostatin; dinileukin diftitox; N-acetyl-cysteine; sirolimus; and visulizumab. | Biological | Conventional Second-line Treatment |
Primary outcome
Number of Participants With Overall Response at 28 Days
Time frame: 28 days for OR
The change in grade from baseline to Study Day 28 (-1/+2 day) was used to determine the response of GvHD to treatment using the following classifications: * Complete response (CR): complete resolution of all signs of GvHD. * Partial response (PR): improvement of 1 overall grade (i.e., change from baseline in IBMTR to a less severe grading). * Stable disease (SD): No change in GvHD grading (i.e., no change from baseline in IBMTR grade). * Disease progression (PD): Deterioration in one overall grade in GvHD (i.e., worsening in IBMTR by at least 1 grade compared to baseline). * Death
3 secondary outcomes
Number of Participants With Overall Survival (OS) up to 180 Days
Time frame: Time frame is up to 180 days
BEGEDINA Serum Concentrations Pre- and 15 Minutes Post-Infusion
Time frame: Time frame is up to Day 28
Number of Participants With Adverse Events
Time frame: The safety parameters were analysed at the end of the study period (Day 180)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Graft vs Host Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrea Bacigalupo, MD principal investigator
27 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Begelomab and Conventional Second-line Treatment in people with Graft vs Host Disease, run by Adienne SA at 27 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, Italy, Spain, France, Germany and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Overall Response at 28 Days (time frame: 28 days for OR). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2020.