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

ReAlta Life Sciences

Status and phase: Enrolling; Phase 2

Conditions: Steroid Refractory GVHD

Treatments: Drug: RLS-0071

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06343792

RLS-0071-203

Details and patient eligibility

About

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.

Enrollment: 66 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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66 participants in 8 patient groups

RLS-0071Cohort 1

Experimental group

Description:

10 mg/kg Q8H RLS-0071 for 7 days

Treatment:

Drug: RLS-0071

RLS-0071 Cohort 2

Experimental group

Description:

40 mg/kg Q8H RLS-0071 for 7 days

Treatment:

Drug: RLS-0071

RLS-0071 Cohort 3

Experimental group

Description:

10 mg/kg Q8H RLS-0071 for 14 days with concurrent ruxolitinib

Treatment:

Drug: RLS-0071

RLS-0071 Cohort 4

Experimental group

Description:

40 mg/kg Q8H RLS-0071 for 14 days with concurrent ruxolitinib

Treatment:

Drug: RLS-0071

RLS-0071 Cohort 5

Experimental group

Description:

10 mg/kg Q8H RLS-0071 for 7 days and then 10 mg/kg QD RLS-0071 for 7 days with concurrent ruxolitinib

Treatment:

Drug: RLS-0071

RLS-0071 Cohort 6

Experimental group

Description:

40 mg/kg Q8H RLS-0071 for 7 days and then 40 mg/kg QD RLS-0071 for 7 days with concurrent ruxolitinib

Treatment:

Drug: RLS-0071

RLS-0071 Expansion Cohort 1

Experimental group

Description:

12 participants will receive 10 or 40 mg/kg Q8H RLS-0071 for 7 or 14 days

Treatment:

Drug: RLS-0071

RLS-0071 Expansion Cohort 2

Experimental group

Description:

12 participants will receive 10 or 40 mg/kg Q8H RLS-0071 for 7 or 14 days

Treatment:

Drug: RLS-0071