Study of R289 in Participants With Lower-risk Myelodysplastic Syndromes (LR MDS)

• ClinicalTrials.gov Identifier: NCT05308264
• Recruitment Status: Recruiting
• First Posted: April 4, 2022
• Last Update Posted: October 10, 2023
• Sponsor: Rigel Pharmaceuticals
• Information provided by (Responsible Party): Rigel Pharmaceuticals

Tracking Information

• First Submitted Date: March 2, 2022
• First Posted Date: April 4, 2022
• Last Update Posted Date: October 10, 2023
• Actual Study Start Date: September 12, 2022
• Estimated Primary Completion Date: May 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 25, 2022)

Safety and Tolerability [ Time Frame: 2 Year ]

• Incidence of adverse events (AEs)
• Incidence of discontinuation or interruptions of R289 due to AEs
• Incidence of dose limiting toxicities (DLTs)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 6, 2023)

• Participants with red blood cell transfusion independence by Week 24 [ Time Frame: 24 Weeks ]
  Proportion of participants who achieve ≥ 50% reduction in number of red blood transfusion compared to baseline and ≥ 24 weeks.
• Characterize pharmacokinetics (PK) [ Time Frame: 8 Weeks ]
  Maximum plasma concentration (Cmax)

• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: October 26, 2022)

Characterize pharmacodynamic (PD) [ Time Frame: 1 year ]

Change from baseline biomarker expression levels in plasma and bone marrow (including but not limited to, C-reactive protein [CRP] and tumor necrosis factor [TNF]-a)

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of R289 in Participants With Lower-risk Myelodysplastic Syndromes (LR MDS)
• Official Title: An Open-label, Phase 1b Study of R289, an IRAK1/4 Inhibitor, in Participants With Lower-risk Myelodysplastic Syndromes (LR MDS) Who Are Refractory/Resistant to Prior Therapies
• Brief Summary: Phase 1b Study of R289 in Participants with Lower-risk Myelodysplastic Syndromes (LR MDS)
• Detailed Description: An open-label, Phase 1b study of R289 to determine tolerability and preliminary efficacy in participants with LR MDS who are relapsed, refractory/resistant, intolerant, or have inadequate response to prior therapies such as erythropoietin (EPO), thrombopoietin (TPO), luspatercept, or hypomethylating agents (HMAs) for MDS.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Low Risk Myelodysplastic Syndromes

Intervention

Drug: R906289 Monosodium (R289 Na)

Drug: R906289 Monosodium (R289 Na) R906289 Monosodium (250mg PO qd,500 mg PO qd, 750 mg PO qd, 1000 mg PO qd)

Other Name: R906289 Monosodium

Study Arms

Experimental: Experimental

Dose Level 1: 250mg PO qd Dose Level 2: 500mg PO qd Dose Level 3: 750 mg PO qd and 1000 mg PO qd

Intervention: Drug: R906289 Monosodium (R289 Na)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 6, 2023): 34
• Original Estimated Enrollment (submitted: March 25, 2022): 40
• Estimated Study Completion Date: May 2025
• Estimated Primary Completion Date: May 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participant must be ≥ 18 years of age at the time of signing the informed consent.
• Must have definitive diagnosis of MDS with very low, low, or intermediate-1 risk (International Prognostic Scoring System (IPSS)-R ≤ 3.5) and ≤5% bone marrow myeloblasts.
• Must be relapsed, refractory/resistant, intolerant, or have inadequate response to therapies with known clinical benefits for MDS, such as TPOs, EPOs, luspatercept, and HMAs(i.e., azacytidine or decitabine). Participants with del (5q) must have failed prior lenalidomide therapy.

• Must be blood transfusion dependent and meet at least one of the disease-related criteria for RBC transfusion, or platelet count within 8 weeks prior to initial administration of study treatment:

  1. Symptomatic anemia untransfused with hemoglobin < 9.0 g/dL within 8 weeks of registration or red blood cell (RBC) transfusion dependent defined as receiving ≥ 2 units of packed red blood cells (PRBCs) within 8 weeks in the preceding 16 weeks for a hemoglobin <9.0 g/dL.
  2. Clinically relevant thrombocytopenia (platelet counts of <100 × 109/L in at least 2 blood counts prior to study treatment and transfusion dependence).

All participants must have documented marrow iron stores. If marrow iron stain is not available, the transferrin saturation must be >20% or a serum ferritin > 100ng/100mL

• Must have Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 at screening.

• Must have adequate organ function, defined as:

  1. Hepatic function:

     • aspartate amino transferase (AST) or alanine aminotransferase (ALT) ≤ 1.5 × upper limit of normal (ULN)
     • total bilirubin ≤ 1.5 × ULN
  2. Renal function defined as creatinine clearance > 60 mL/min (using Cockcroft-Gault), or blood creatine < 1.5 mg/dL

Exclusion Criteria:

• Prior treatment for MDS (i.e., TPOs, EPOs, luspatercept, HMAs) concluded < 4 weeks prior to study treatment
• Clinically significant anemia resulting from iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis, or GI bleeding.
• MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases.
• Diagnosis of chronic myelomonocytic leukemia.
• History of uncontrolled seizures.
• Uncontrolled bacterial or viral infection (i.e., documented HIV, hepatitis B or hepatitis C).

• History of an active malignancy within the past 2 years prior to study entry, with the exception of:

  1. Adequately treated in situ carcinoma of the cervix uteri
  2. Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin, or
  3. Any other malignancy with a life expectancy of more than 2 years
• History of or active, clinically significant, cardiovascular, respiratory, GI, renal, hepatic, neurological, psychiatric, musculoskeletal, genitourinary, dermatological, or other disorder that, in the Investigator's opinion, could affect the conduct of the study or the absorption, metabolism or excretion of the study treatment.
• Prior history of bone marrow transplantation.
• Marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 480 milliseconds [msec]) (Common Terminology Criteria for Adverse Events [CTCAE] Grade 1) using Fridericia's QT correction formula.
• History of additional risk factors for TdP (e.g., symptomatic heart failure with left ventricular ejection fraction [LVEF] <40%, hypokalemia, family history of Long QT Syndrome).
• Receiving any other concurrent chemotherapy, radiotherapy, or immunotherapy (within 2 weeks of initiating study treatment), or the toxicity of the relevant prior treatment has not been resolved yet.
• Use of concomitant medications that prolong the QT/QTc interval during study treatment
• Use of concomitant medications that are strong CYP3A or CYP2B6 inhibitors or inducers during study treatment

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Elizabeth Franklin; (650) 624-1100; clinicaltrials@rigel.com

Contact: Donna Chow; (650) 624-1100; clinicaltrials@rigel.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05308264
• Other Study ID Numbers: C-906289-002
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Rigel Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Rigel Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Rigel Pharmaceuticals
• Verification Date: October 2023