Steroid Refractory GVHD
Conditions
Brief summary
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.
Interventions
DRUGRLS-0071
RLS-0071 will be administered for 7 or 14 days according to the assigned dose group.
Sponsors
CTI Clinical Trial and Consulting Services
ReAlta Life Sciences, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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 * 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with treatment-related adverse events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Day 1 to Day 180 |
| Overall Response Rate (ORR) of RLS-0071 | Day 1 to Day 28 |
Secondary
| Measure | Time frame |
|---|---|
| Initiation of additional or alternative treatment(s) for aGvHD (including an increase in steroid dose to >2 mg/kg methylprednisolone equivalent) | Day 1 - Day 180 |
| Change or shift in Stage for lower GI aGvHD, liver aGvHD, skin aGvHD, or upper GI aGvHD from baseline based on MAGIC Criteria | Days 7, 14, 28, 56, and 180 |
| Attainment of Stage 0 or 1 lower GI aGvHD, liver aGvHD, skin aGvHD, or upper GI aGvHD | Days 7, 14, 28, 56, and 180 |
| Incidence of refractoriness (to RLS-0071 +/- ruxolitinib) | Days 7, 14, 28, 56, and 180 |
| Overall survival | Day 1 - Day 180 |
| Non-relapse mortality | Day 1 - Day 180 |
| Duration of hospital stay | Day 1 - Day 180 |
| Change or shift in overall Grade of aGvHD | Day 0 - Days 7, 14, 28, 56, and 180. |
| Overall corticosteroid use | Days 7, 14, 28, 56, and 180 |
Countries
Germany, Spain, United States
Contacts
Primary ContactLinda Dell, MBA
Outcome results
None listed