Overview
This study is a Open Label Prospective Dose-Ranging Escalation and Expansion Trial to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Dosing, and Efficacy of RLS-0071 for the secondary treatment of acute Graft-versus-Host Disease (aGvHD) in hospitalized patients who are steroid-refractory.
Eligibility
Inclusion Criteria:
- Male or female adults or adolescents (>12 years old).
- Hospitalized with steroid-refractory aGvHD (grade II-IV) after allo-HSCT
- Anticipated hospital length-of-stay of at least 1 week from the time of RLS-0071 initiation.
- No plans to add additional GvHD treatment medications or to add, dose-adjust, or discontinue GvHD prophylactic medications during the 7-days of RLS-0071 treatment.
- Neutrophil recovery following the stem-cell transplantation, defined as blood neutrophil count >500/mL for at least 3 consecutive measurements and not supported by growth factor supplementation
- Weight >40 kg and ≤ 140 kg at screening.
Exclusion Criteria:
- Has received more than 1 allo-HSCT
- Current, previous, or planned use of any systemic treatment in addition to or other than corticosteroids or ruxolitinib for aGvHD
- Previous failure of ruxolitinib treatment
- Uncontrolled GI infection
- Endoscopic and biopsy testing (if performed) that definitively rules out lower GI aGvHD
- Chronic GvHD
- Participants with evidence of relapsed primary disease, or participants who have been treated for relapse after the allo-HSCT was performed.
- Unresolved toxicity or complications (other than aGvHD) due to the allo-HSCT
- Any corticosteroid therapy for indications other than aGvHD at doses of methylprednisolone or equivalent >1 mg/kg per day within 7 days of enrollment.
- Severe organ dysfunction unrelated to underlying aGvHD
- Known hypersensitivity, allergy, or anaphylactic reaction to polyethylene glycol (PEG)
- Significant liver disease that is unrelated to GvHD
- Moderate to severe kidney disease
- Currently breast feeding.
- Known pregnancy, a positive pregnancy test at screening, or lactation for WOCBP.
- Active hepatitis B virus (HBV) or hepatitis C virus infection that requires treatment or human immunodeficiency virus (HIV)-1 or HIV-2.
- Active sepsis