Study of IL-22 IgG2-Fc (F-652) for Subjects With Grade II-IV Lower GI aGVHD

Inclusion Criteria

• Age ≥18 years and ≤80.
• Newly diagnosed lower GI grade II-IV aGVHD with clinical diagnosis based on modified Keystone criteria1 following allogeneic HSCT using bone marrow, peripheral blood stem cells, or cord blood. Grading of aGVHD will be based on International Bone Marrow Transplant Registry (IBMTR) criteria.
• Subjects are willing to undergo a biopsy to confirm lower GI aGVHD. Biopsy results are not needed to initiate treatment. However, if aGVHD is not confirmed histologically, treatment with F-652 will be discontinued.
• Female subjects of childbearing potential who agree to practice 2 effective methods of contraception.
• Male subjects, even if surgically sterilized (i.e. Status post-vasectomy) must agree to agree to practice contraception.
• Have adequate renal function (Serum creatinine 500/mm3.
• Show evidence of a personally signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all pertinent aspects of the trial.

Exclusion Criteria

Subjects who met any of the following criteria were excluded from the study:

• Evidence of relapse or progression of hematologic malignancy at the time of study enrollment.
• Active uncontrolled infection. Subjects with a controlled infection receiving definitive therapy for 48 hours prior to enrollment were eligible.
• Subjects requiring vasopressors or mechanical ventilation.
• Subjects who had received previous systemic corticosteroids for the treatment of acute GI GVHD for longer than 5 days. Subjects who were treated with systemic corticosteroids for aGVHD for a prior allogeneic HSCT >12 months ago were eligible.
• Subjects who received any corticosteroid therapy (for non-GVHD) at doses >0.5 mg/kg/day prednisone (or IV equivalent) within 7 days prior to the onset of GVHD therapy.
• Subjects who developed aGVHD after unplanned donor lymphocyte infusion.
• Subjects with chronic GVHD features (i.e., acute/chronic GVHD overlap syndrome or classical chronic GVHD).
• History of psoriasis.
• History of epithelial malignancies including melanoma or any carcinomas.
• History or diagnosis of mantle cell lymphoma or anaplastic large cell lymphoma.
• Subject was pregnant or breast-feeding.
• Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
• The subject or guardian was unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, follow-up, and research tests.
• The subject had tested positive for the Clostridium difficile (C. difficile) toxin within 7 days of study entry.
• Cytotoxic, biologic, or investigational agents were not permitted throughout the study. These included, but were not limited to, ATG, alemtuzumab, rituximab, photopheresis, and thalidomide. Subjects who participated in any other investigational drug trial or had exposure to any other investigational agent, device, or procedure, within 4 weeks prior to screening and throughout the entire trial, except for trials of investigational drugs administered prophylactically for GVHD or CMV post-allogeneic HSCT. In this exception, the other investigational drug must have been discontinued upon enrolling (i.e., screening/sign ICF) into this study.
• Any serious medical or psychiatric illness that could, in the Investigator's opinion, potentially have interfered with the completion of treatment according to this protocol.