Safety and Efficacy Study of T-Guard to Treat Steroid-resistant Acute GVHD

The experimental design is a bicentric non-controlled fixed-dose Phase I/II study. A total of 20 adult patients with acute steroid-resistant GVHD will be enrolled in a 12 months period. The treatment consists of a standard dose of 4 infusions T-Guard (4 mg/m2), given 48-hours apart over a 4-hour period. The intended follow-up period is 6 months.

The primary objective is to determine the efficacy of T-Guard, 4 weeks after the first infusion (Day 28), in inducing an objective clinical response in patients with acute GVHD refractory to standard first line corticosteroid therapy.

Secondary objectives are:

• To evaluate the overall safety and efficacy of T-Guard during the first 6 months after imitation of therapy;
• To determine the pharmacokinetic profile of T-Guard;
• To determine the immunogenicity of T-Guard.

Exploratory objectives are:

• To study the specificity and kinetics of the treatment-induced depletion and subsequent repopulation of lymphocyte subsets;
• To evaluate diagnostic and predictive GVHD biomarkers relative to treatment outcomes.

Inclusion criteria

• Patients suffering from acute GVHD which is staged Grade II-IV 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.

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 (> 3 mg/dl), or having a serum albumin level of 15 g/l or less.
• Patients having uncontrolled bacterial, viral or fungal infections, at the discretion of the investigator, at the start of therapy.
• Patients with current signs or symptoms of active intrapulmonary disease.
• Patients with known hypersensitivity to any of the components of the study drug.
• 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 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.