Clinical Trial 23639

• Overview

  Study 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

  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.

  Objective:

  Primary: Demonstrate safety and tolerability of RLS-0071 in the treatment of aGvHD. Determine Overall Response Rate (ORR) of RLS-0071 at 28 days. Secondary: Determine Complete Response (CR) Rate, Very Good Partial Response (VGPR) Rate, and Partial Response (PR) Rate at 7, 14, 28, 56, and 180 days. Determine ORR at 7, 14, 56, and 180 days. Determine ORR, and CR Rate, VGPR Rate, and PR Rate at 7, 14, 28, 56, and 180 days based on lower gastrointestinal (GI) response only (overall study population and for the subset with lower GI aGvHD). Assess refractoriness to RLS-0071 +/- ruxolitinib. Determine need for initiation of additional or alternative treatments for aGvHD. Evaluate change in Stage and attainment of Stage 0 or 1 for lower GI aGvHD, liver aGvHD, skin aGvHD, and upper GI aGvHD, and overall aGvHD Grade from baseline to Days 7, 14, 28, 56, and 180. Assess loss of response, reduction in response, or occurrence of flare in participants who had an initial response to RLS-0071 (with systemic corticosteroids and +/- ruxolitinib). Evaluate dose response (dose and duration) for the primary and secondary efficacy endpoints. Characterize overall survival, failure-free survival, and non-relapse mortality. Characterize Pharmacokinetics (based on sparse sampling for all participants and intensive sampling for a subset of participants) of RLS-0071. Evaluate aGvHD patient outcomes: FACT-BMT, abdominal pain, volume/frequency of diarrhea, food tolerance and use of total parenteral nutrition (TPN), and duration of hospital stay. Evaluate change in Mount Sini Acute GVHD International Consortium (MAGIC) biomarkers (ST2 and REG3α) from Baseline to Days 7, 14, and 28.

• Treatments

  Therapies:

  Janus kinase (JAK) inhibitor; Therapy (NOS)

  Medications:

  Jakafi (Ruxolitinib); RLS-0071 (); Ruxolitinib ()

• Inclusion Criteria

  Inclusion Criteria:
  • Over 18 years of age
  • 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.
  • Other criteria may apply

• Exclusion Criteria

  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

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