Acute Graft-versus-Host Disease (GVHD) not responding on regular first line therapy of 2 mg/kg corticosteroids daily. MedDRA version: 17.1 Level: LLT Classification code 10068908 Term: AGVHD System Organ Class: 100000004870
Conditions
Interventions
Product Name: A mixuture of mAb SPV-T3a-ricin A chain fusion protein and mAb WT1-ricin A chain fusion protein
Product Code: T-Guard
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Anti
Sponsors
Xenikos BV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients suffering from acute GVHD which is staged as Grade II-IV (Appendix 1) according to the modified Glucksberg Criteria and progressing after 3 days, or not improving after 7 days, of methylprednisolone at a dose of 2 mg/kg per day. - Age = 18 years. - Patients or an impartial witness (in case the patient is capable to provide verbal consent but not capable to sign the informed consent) should have given written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 16 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: - Patients receiving concomitant investigational therapeutics for acute GVHD, including investigational agents used for GVHD prophylaxis, at the time of enrollment. - Patients with signs or symptoms suggestive of chronic GVHD. - Patients requiring mechanical ventilation, requiring vasopressor support, requiring hemodialysis, having serum creatinine > 266 µmol/l (> 3mg/dl), or having a serum albumin level of 15 g/l or less. - Patients having uncontrolled infections. - Patients with current signs or symptoms of active intrapulmonary disease. - Patients with known hypersensitivity to any of the components of the study drug (murine mAb or RTA). - Female patients who are pregnant, breast feeding, or, if sexually active, unwilling to use effective birth control for the duration of the study. - Male patients who are, if sexually active, unwilling to use effective birth control for 30 days after the last infusion. - Patients participating in a clinical trial with another investigational medicinal product within 30 days prior to providing informed consent. - Patients whose decision to participate might be unduly influenced by perceived expectation of gain or harm by participation, such as patients in detention due to official or legal order.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy with which T-Guard, four weeks after the first infusion (study Day 28) induces an objective clinical response in patients with steroid-resistant acute GVHD.;Secondary Objective: Secondary objectives: - To evaluate the overall safety and efficacy of T-Guard during the first 6 months after initiation of therapy. - To determine the pharmacokinetic profile of T-Guard. - To determine the immunogenicity of T-Guard Exploratory objectives: - To study the specificity and kinetics with which T-Guard depletes T cells and NK cells and ‘resets’ the T-cell compartment. - To evaluate diagnostic and predictive GHVD biomarkers relative to treatment outcomes. ;Primary end point(s): The acute GVHD response rate at 4 weeks after the first infusion of T-Guard (Day 28), being defined as the fraction of patients showing a complete or partial response (CR plus PR).;Timepoint(s) of evaluation of this end point: Four weeks after initiation of treatment, study Day 28. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): SECONDARY ENDPOINTS - The safety and tolerability of T-Guard, as assessed by evaluating DLT´s, adverse and serious adverse events reporting during 6 months after initiation of treatment. - The proportion of patients receiving a very good partial response (VGPR) of their acute GVHD at 4 weeks after the first infusion (Day 28). - The acute GVHD relapse rate during 6 months after initiation of treatment. - The incidence of chronic GVHD during 6 months after initiation of treatment. - The overall survival and progression-free survival during 6 months after initiation of treatment. - The pharmacokinetic profile of T-Guard as determined on blood samples drawn during the administration period until 2 days after the last infusion. - The occurrence and extent of humoral responses against T-Guard (anti-drug-antibodies, ADA) as determined on blood samples drawn at pre-treatment and at 1, 3 and 6 months after the first infusion. - The occurrence of treatment-induced cytokine release, as determined on blood samples drawn at t = 0 (pre-dose), 1 and 4 hours after starting of each infusion. EXPLORATORY ENDPOINTS - The kinetics and specificity of treatment-induced T cell and NK cell depletion as measured on blood samples drawn during the administration period until 2 days after the last dose, and then weekly until 8 weeks, and than at 3 and 6 months after the first infusion. - The composition and evolution of the T-, B- and NK-cell compartments at pre-treatment and at 4 weeks, 3 and 6 months after the first infusion. - The composition and evolution of the T-cell receptor (TCR) Vbeta repertoire at pre-treatment and at 4 weeks, 3 and 6 months after the first infusion. - The identification and evolution of host-reactive T-cell clones at pre-treatment and at 4 weeks, 3 and 6 months after the first infusion. - The measurement of diagnostic and predictive GVHD biomarkers relative to treatment outcomes, including citrulline, CRP, elafin, IL-8, TNFR1, I | — |
Countries
Germany, Netherlands
Contacts
Public ContactYpke van Oosterhout
Xenikos
Outcome results
None listed