A Phase I Study of Neihulizumab (AbGn-168H) in Patients With Steroid-refractory Acute Graft-versus-host Disease (Sr-aGvHD)
To establish the pharmacokinetic, pharmacodynamic, safety and efficacy profiles of Neihulizumab in patients with steroid-refractory acute graft-versus-host disease(sr-aGvHD)
18 Years and up
Accepting Healthy Volunteers?
1. Patients must have clinical aGvHD and pathologic findings consistent with the diagnosis by biopsy of at least 1 involved site and treated initially with steroids at prednisone-equivalent doses ≥1 mg/kg/day, and
(i) worsening of GvHD manifestations across any interval of at least 2 days before tapering of steroid doses has begun, or
(ii) persistence of grade II to IV aGvHD across any interval of at least 7 days without improvement during steroid treatment at any prednisone-equivalent dose >0.4 mg/kg/day or at any lower dose in patients with contraindication to continued treatment at higher steroid doses because of severe steroid-related toxicity (e.g., myopathy), or
(iii) initial response of GvHD manifestations followed by exacerbation of aGvHD across any interval of at least 3 days while tapering glucocorticoid treatment at any prednisone-equivalent dose >0.4 mg/kg/day or at any lower dose in patients with contraindication to continued treatment at higher steroid doses because of severe steroid-related toxicity (e.g., myopathy).
2. Patients must have erythematous manifestations of cutaneous aGvHD. Characteristics of the rash must indicate active inflammation (red coloration) as distinct from resolving inflammation (brown coloration).
3. Providers and patients must be willing to defer new systemic or cutaneous topical treatment of aGvHD for at least 36 hours after administration of Neihulizumab.
4. Patient must give informed consent and sign an approved consent form prior to any study procedures.
5. Females of childbearing potential must have a negative pregnancy test result before enrollment. Males and females of childbearing potential must agree to use a highly effective method of birth control during the study for at least 30 days after enrollment in the study.
Exclusion Criteria (may not meet any of the following criteria):
1. Uncontrolled infections not responding to antimicrobial therapy or requiring intensive critical care or vasopressors
2. Evidence of end-organ Cytomegalovirus (CMV) infection
3. Patients known to have CMV, adenovirus, human herpes virus 6 (HHV6), Epstein Barr virus (EBV) or any hepatitis viremia from screening according to institutional standard practice
4. HIV infection or a known HIV-related malignancy.
5. Tuberculosis, history of tuberculosis or a known positive Quantiferon test for tuberculosis
6. Unplanned donor lymphocyte infusion (DLI) for residual or relapsed malignancy or mixed chimerism. DLI as part of the planned HCT protocol is allowed.
7. Known relapsed or progressive malignancy after transplant, post-transplant lymphoproliferative disease or any secondary malignancy diagnosed after HCT
8. Absolute neutrophil count (ANC) <1000/mm3
9. Total serum bilirubin concentration >3.0 mg/dL UNLESS attributed to GvHD
10. Creatinine clearance < 40 mL/min calculated by Cockcroft-Gault equation.
11. Sodium (Na) concentration < 130 mmol/L.
12. Ileus, abdominal pain, extensive denudation of intestinal mucosa or stage 4 GI GvHD.
13. Karnofsky Performance Status (KPS) <50%
14. Intensive care unit (ICU) care, life expectancy of less than 28 days, ongoing or unresolved hepatic sinusoidal obstruction syndrome, unstable hemodynamics, or evidence of current or previous clinically significant disease, medical condition or finding (including vital signs and ECG) that in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data
15. History of allergy or hypersensitivity to any systemically administered antibody agent or its excipients
16. Pregnancy or nursing
17. Prior treatment with anti-lymphocyte globulin or anti-thymocyte globulin
18. Patients <18 years of age