Clinical trial NCT06343792: Safety, PK, PD, Dosing, and Efficacy of RLS-0071for the Treatment of Hospitalized Patients with Steroid-Refractory Acute Graft-versus-Host Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Steroid Refractory GVHD
Lead sponsor: ReAlta Life Sciences, Inc.
Sponsor class: INDUSTRY
Collaborators: name: CTI Clinical Trial and Consulting Services
First posted: 2024-04-03
Enrollment: 66
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with treatment-related adverse events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: Day 1 to Day 180
measure: Overall Response Rate (ORR) of RLS-0071
timeFrame: Day 1 to Day 28
Secondary outcomes:
measure: Incidence of refractoriness (to RLS-0071 +/- ruxolitinib)
timeFrame: Days 7, 14, 28, 56, and 180
measure: Overall corticosteroid use
timeFrame: Days 7, 14, 28, 56, and 180
measure: Initiation of additional or alternative treatment(s) for aGvHD (including an increase in steroid dose to >2 mg/kg methylprednisolone equivalent)
timeFrame: Day 1 - Day 180
measure: Change or shift in Stage for lower GI aGvHD, liver aGvHD, skin aGvHD, or upper GI aGvHD from baseline based on MAGIC Criteria
timeFrame: Days 7, 14, 28, 56, and 180
measure: Attainment of Stage 0 or 1 lower GI aGvHD, liver aGvHD, skin aGvHD, or upper GI aGvHD
timeFrame: Days 7, 14, 28, 56, and 180
measure: Change or shift in overall Grade of aGvHD
timeFrame: Day 0 - Days 7, 14, 28, 56, and 180.
measure: Overall survival
timeFrame: Day 1 - Day 180
measure: Non-relapse mortality
timeFrame: Day 1 - Day 180
measure: Duration of hospital stay
timeFrame: Day 1 - Day 180
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Site 0191
state: California
city: Los Angeles
country: United States
facility: Site 1343
state: California
city: Atlanta
country: United States
facility: Site 1318
state: Georgia
city: Saint Louis
country: United States
facility: Site 1068
state: Missouri
city: Columbus
country: United States
facility: Site 1382
state: Ohio
city: Sevilla
country: Spain
facility: Site 3101
state: SE
Study officials:
References: