Safety, PK, PD, Dosing, and Efficacy of RLS-0071for the Treatment of Hospitalized Patients With Steroid-Refractory Acute Graft-versus-Host Disease (AURORA)

Phase 2 Open Label Prospective Dose-Ranging Clinical Trial With Escalation and Expansion Cohorts to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Dosing, and Efficacy of RLS-0071 for the Treatment of Hospitalized Patients With Steroid-Refractory Acute Graft-versus-Host Disease

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Steroid Refractory GVHD
• Intervention / Treatment: Drug: RLS-0071

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RLS-0071Cohort 1; 10 mg/kg Q8H RLS-0071 for 7 days	Drug: RLS-0071; RLS-0071 will be administered for 7 or 14 days according to the assigned dose group.
Experimental: RLS-0071 Cohort 2; 40 mg/kg Q8H RLS-0071 for 7 days	Drug: RLS-0071; RLS-0071 will be administered for 7 or 14 days according to the assigned dose group.
Experimental: RLS-0071 Cohort 3; 10 mg/kg Q8H RLS-0071 for 14 days with concurrent ruxolitinib	Drug: RLS-0071; RLS-0071 will be administered for 7 or 14 days according to the assigned dose group.
Experimental: RLS-0071 Cohort 4; 40 mg/kg Q8H RLS-0071 for 14 days with concurrent ruxolitinib	Drug: RLS-0071; RLS-0071 will be administered for 7 or 14 days according to the assigned dose group.
Experimental: RLS-0071 Cohort 5; 10 mg/kg Q8H RLS-0071 for 7 days and then 10 mg/kg QD RLS-0071 for 7 days with concurrent ruxolitinib	Drug: RLS-0071; RLS-0071 will be administered for 7 or 14 days according to the assigned dose group.
Experimental: RLS-0071 Cohort 6; 40 mg/kg Q8H RLS-0071 for 7 days and then 40 mg/kg QD RLS-0071 for 7 days with concurrent ruxolitinib	Drug: RLS-0071; RLS-0071 will be administered for 7 or 14 days according to the assigned dose group.
Experimental: RLS-0071 Expansion Cohort 1; 12 participants will receive 10 or 40 mg/kg Q8H RLS-0071 for 7 or 14 days	Drug: RLS-0071; RLS-0071 will be administered for 7 or 14 days according to the assigned dose group.
Experimental: RLS-0071 Expansion Cohort 2; 12 participants will receive 10 or 40 mg/kg Q8H RLS-0071 for 7 or 14 days	Drug: RLS-0071; RLS-0071 will be administered for 7 or 14 days according to the assigned dose group.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
Incidence of refractoriness (to RLS-0071 +/- ruxolitinib)	Days 7, 14, 28, 56, and 180
Overall corticosteroid use	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
Attainment of Stage 0 or 1 lower GI aGvHD, liver aGvHD, skin aGvHD, or upper GI aGvHD	Days 7, 14, 28, 56, and 180
Change or shift in overall Grade of aGvHD	Day 0 - 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

Collaborators and Investigators

• Sponsor: ReAlta Life Sciences, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: March 14, 2024
• First Submitted That Met QC Criteria: March 26, 2024
• First Posted (Actual): April 3, 2024

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: RLS-0071-203

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No