Safety, PK, PD, Dosing, and Efficacy of RLS-0071for the Treatment of Hospitalized Patients with Steroid-Refractory Acute Graft-versus-Host Disease
- Registration Number
- NCT06343792
- Lead Sponsor
- ReAlta Life Sciences, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 66
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description RLS-0071Cohort 1 RLS-0071 10 mg/kg Q8H RLS-0071 for 7 days RLS-0071 Expansion Cohort 2 RLS-0071 12 participants will receive 10 or 40 mg/kg Q8H RLS-0071 for 7 or 14 days RLS-0071 Cohort 3 RLS-0071 10 mg/kg Q8H RLS-0071 for 14 days with concurrent ruxolitinib RLS-0071 Cohort 4 RLS-0071 40 mg/kg Q8H RLS-0071 for 14 days with concurrent ruxolitinib RLS-0071 Expansion Cohort 1 RLS-0071 12 participants will receive 10 or 40 mg/kg Q8H RLS-0071 for 7 or 14 days RLS-0071 Cohort 2 RLS-0071 40 mg/kg Q8H RLS-0071 for 7 days RLS-0071 Cohort 5 RLS-0071 10 mg/kg Q8H RLS-0071 for 7 days and then 10 mg/kg QD RLS-0071 for 7 days with concurrent ruxolitinib RLS-0071 Cohort 6 RLS-0071 40 mg/kg Q8H RLS-0071 for 7 days and then 40 mg/kg QD RLS-0071 for 7 days with concurrent ruxolitinib
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Duration of hospital stay Day 1 - Day 180 Non-relapse mortality Day 1 - Day 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 Overall survival 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 Incidence of refractoriness (to RLS-0071 +/- ruxolitinib) Days 7, 14, 28, 56, and 180 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
Trial Locations
- Locations (6)
Site 0191
🇺🇸Duarte, California, United States
Site 1343
🇺🇸Los Angeles, California, United States
Site 1318
🇺🇸Atlanta, Georgia, United States
Site 1068
🇺🇸Saint Louis, Missouri, United States
Site 1382
🇺🇸Columbus, Ohio, United States
Site 3101
🇪🇸Sevilla, SE, Spain