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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
EU CTIS ID: 2024-510582-42-02
What this study is testing
Demonstrate safety and tolerability of RLS-0071 in the treatment of acute graft versus host disease (aGvHD). Determine Overall Response Rate (ORR) of RLS-0071 at 28 days.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Male or female adults or adolescents (>12 years old).
- Neutrophil recovery following the stem-cell transplantation, defined as blood neutrophil count >500/mL for at least 3 consecutive measurements (use of growth factor supplementation, e.g., filgrastim, at that time is permitted).
- At the time of study screening prior to RLS-0071 initiation: a)Neutrophil count >1000/mL (not supported by growth factor supplementation, e.g., filgrastim); b) Platelet count >50,000/ml (not supported by platelet transfusions); c) Aspartame aminotransferase (AST) and alanine aminotransferase (ALT) < 5 times the upper limit of normal (ULN); d) Serum bilirubin < 6mg/dL; and e) Adequate coagulation function (e.g., prothrombin time (PT)/international normalized ratio (INR) and activated partial thromboplastin time (aPPT)/partial thromboplastin time (PTT) <2 X ULN.
- Weight >40 kg and ≤ 140 kg at screening.
- Participant (or legally authorized representative for minors) provides written informed consent; additionally, informed assent for minors.
- Able to communicate well with the Investigator and/or study site personnel and to comply with the requirements of the entire study.
You likely can't join if
- Has received more than 1 allo-HSCT.
- Severe organ dysfunction unrelated to underlying aGvHD, including: a) Cholestatic disorders or unresolved veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to GvHD and ongoing organ dysfunction) b) Clinically significant or uncontrolled cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, circulatory collapse requiring vasopressor or inotropic support, or arrhythmia that requires therapy. c) Clinically significant respiratory disease that requires mechanical ventilation support or oxygen supplementation.
- Known hypersensitivity, allergy, or anaphylactic reaction to polyethylene glycol (PEG) or PEG containing material.
- Significant liver disease that is unrelated to GvHD
- Severe kidney disease, with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 (chronic kidney disease [CKD] Stages 4-5).
- Participation in any clinical research study evaluating an investigational product (IP) or therapy for GvHD prophylaxis or treatment within 1 month and less than 5 half-lives of IP prior to the Screening visit.
See the full eligibility criteria
Who can join
- Male or female adults or adolescents (>12 years old).
- Neutrophil recovery following the stem-cell transplantation, defined as blood neutrophil count >500/mL for at least 3 consecutive measurements (use of growth factor supplementation, e.g., filgrastim, at that time is permitted).
- At the time of study screening prior to RLS-0071 initiation: a)Neutrophil count >1000/mL (not supported by growth factor supplementation, e.g., filgrastim); b) Platelet count >50,000/ml (not supported by platelet transfusions); c) Aspartame aminotransferase (AST) and alanine aminotransferase (ALT) < 5 times the upper limit of normal (ULN); d) Serum bilirubin < 6mg/dL; and e) Adequate coagulation function (e.g., prothrombin time (PT)/international normalized ratio (INR) and activated partial thromboplastin time (aPPT)/partial thromboplastin time (PTT) <2 X ULN.
- Weight >40 kg and ≤ 140 kg at screening.
- Participant (or legally authorized representative for minors) provides written informed consent; additionally, informed assent for minors.
- Able to communicate well with the Investigator and/or study site personnel and to comply with the requirements of the entire study.
- Woman participants of childbearing potential (WOCBP) (not surgically sterile) must agree to use highly effective contraception during the study drug treatment period and for 6 additional months following treatment. Follow manufacture recommendation for other medications.
- Male participant with partners of childbearing potential must agree to use highly effective contraception during the study drug treatment period and for 3 additional months following treatment. Follow manufacture recommendation for other medications.
- Have undergone first allogeneic hematopoietic stem cell transplantation (allo-HSCT) from any donor source using bone marrow, peripheral blood stem cells, or cord blood for hematologic malignancies. Recipients of nonmyeloablative and myeloablative conditioning regimens are eligible. Any conditioning regimen and any anti-GVHD prophylactic program are permitted.
- Steroid-refractory aGvHD defined by one or more of the following criteria: progressed after 3 days of treatment with methylprednisolone equivalents (MPE) >2 mg/kg/day; did not improve after 7 days of treatment with MPE >2 mg/kg/day; progressed to a new organ after treatment with MPE >1 mg/kg/day for isolated skin and/or upper GI GvHD; or recurred during or after a steroid taper.
- Grade II-IV aGvHD as per MAGIC guidelines, defined as: a) Grade II: Stage 3 rash and/or Stage 1 liver and/or Stage 1 upper GI and/or Stage 1 lower GI, or b) Grade III: Stage 2 liver and/or Stage 2–3 lower GI, with Stage 0–3 skin and/or Stage 0- 1 upper GI, or c) Grade IV: Stage 4 skin, liver, or lower GI involvement, with Stage 0–1 upper GI
- Hospitalized or being admitted to hospital with aGvHD and a Karnofsky Performance Status (KPS) of at least 50. Inclusion of a participant with a KPS lower than 50 requires discussion with the Medical Monitor.
- Anticipated hospital length-of-stay of at least 1 week from the time of RLS-0071 initiation.
- Initiating or recently initiated ruxolitinib for secondary treatment of aGvHD; if ruxolitinib is contraindicated or the investigator considers it inadvisable for a specific participant then that participant can be enrolled in Cohort 1b or Cohort 2b and not treated with ruxolitinib.
- Feasibility to initiate RLS-0071 dosing simultaneously to ruxolitinib or within 48 hours before or after initiation of ruxolitinib (note that from a timing perspective the goal is simultaneous initiation of RLS-0071 and ruxolitinib whenever possible).
- 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. Note that participants who require treatments for conditions other than aGvHD should receive those treatments, including standard-of-care antifungal prophylaxis, antibiotics for fever, antivirals for CMV, pain medications, dysmotility agents, and TPN, etc.
What rules you out
- Has received more than 1 allo-HSCT.
- Severe organ dysfunction unrelated to underlying aGvHD, including: a) Cholestatic disorders or unresolved veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to GvHD and ongoing organ dysfunction) b) Clinically significant or uncontrolled cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, circulatory collapse requiring vasopressor or inotropic support, or arrhythmia that requires therapy. c) Clinically significant respiratory disease that requires mechanical ventilation support or oxygen supplementation.
- Known hypersensitivity, allergy, or anaphylactic reaction to polyethylene glycol (PEG) or PEG containing material.
- Significant liver disease that is unrelated to GvHD
- Severe kidney disease, with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 (chronic kidney disease [CKD] Stages 4-5).
- Participation in any clinical research study evaluating an investigational product (IP) or therapy for GvHD prophylaxis or treatment within 1 month and less than 5 half-lives of IP prior to the Screening visit.
- Currently breast feeding.
- Any medical or psychiatric condition deemed clinically significant by the Investigator or Sponsor such that: a) Participation of the study would be unsafe, b) OR the condition would make study results uninterpretable.
- Unable or unwilling to cooperate with the site staff for any reason.
- 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.
- Current, previous, or planned (in the initial 7 days) use of any systemic treatment in addition to or other than corticosteroids or ruxolitinib (unless initiated within 48 hours of enrollment per Section 6.1) for aGvHD (previously initiated aGvHD prophylaxis is permitted to continue).
- Active sepsis.
- Previous failure of ruxolitinib treatment.
- Uncontrolled GI infection (e.g., CMV, Cdiff); note that participants with controlled GI infections can be enrolled as long as appropriate anti-infective treatment is initiated and administered.
- Endoscopic and biopsy testing (if performed) that definitively rules out lower GI aGvHD in those who are clinically suspected of having lower GI aGvHD; those participants should not be enrolled or should be discontinued from the study (and will be replaced) unless they otherwise meet the study entry criteria for skin, liver, and/or upper GI aGvHD.
- Chronic GvHD (including presence of GVHD overlap syndrome as per National Institutes of Health [NIH] guidelines).
- RLS0071 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, which in the opinion of the Investigator would pose a safety risk for participation in this trial.
- Any corticosteroid therapy for indications other than aGvHD at doses of methylprednisolone or equivalent >1 mg/kg per day within 7 days of enrollment.
The study team makes the final eligibility decision.
Where it's taking place
- United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 0-17 years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.