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A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study of
IMR-687 in Adult Patients with Sickle Cell Anaemia (Homozygous
HbSS or Sickle-ß0 Thalassemia)
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18-104-1
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A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study of
IMR-687 in Adult Patients with Sickle Cell Anaemia (Homozygous
HbSS or Sickle-ß0 Thalassemia)
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Dr. Biree Andemariam
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A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study of IMR-687 in Adult Patients with Sickle Cell Anaemia (Homozygous HbSS or Sickle-Beta 0 Thalassemia) Background: With a neonatal incidence of 294,000 to 330,000 patients worldwide (Piel 2013), SCA is a rare inherited disorder of red blood cells (RBCs) that is both serious and life threatening. The most common manifestations of SCA include vaso-occlusive crisis, chronic and acute severe pain, acute chest syndrome, stroke, priapism, acute anaemia (particularly from aplastic crisis and splenic sequestration), increased susceptibility to infection, and progressive damage to major organs including the spleen, brain, kidney, heart, lung, skin, retina, vestibular cochlear systems, and bone. In developed countries where there is prenatal Screening and wide spread access to prophylactic and acute interventions, the median age of death remains in the 40s to 50s though many patients succumb to the disease much earlier. Rationale for the study: This is the first study in patients with SCA. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and exploratory pharmacodynamics (PD) and clinical outcomes of IMR-687 in adult patients with SCA. Given that approximately 25% of patients with SCA are currently prescribed HU, it is possible that IMR-687, should it be approved, will be administered as a single agent or co-administered with HU. Therefore, the effects of IMR-687 will be evaluated in patients with SCA who are not receiving HU (Population A) as well as those who are currently receiving a stable dose of HU according to standard of care (Population B). Study design: This is a randomised, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK, and exploratory PD and clinical outcomes of the phosphodiesterase 9 (PDE9) inhibitor, IMR-687. Study population and sample size: 2 populations of patients with SCA: those who are not receiving HU (Population A) and those who are currently receiving a stable dose of HU according to standard of care (Population B). Up to approximately 36 patients will be enrolled in Population A and 18 patients will be enrolled in Population B. Major study interventions: IMR-687 will be supplied as 50, 100 or 200 mg white tablets and will be administered orally with food. Main outcome measures/analyses: Primary Objectives: To assess the safety and tolerability of IMR-687 in adult patients with sickle cell anaemia (SCA), defined as homozygous sickle haemoglobin (HbSS) or sickle-Beta-0 thalassemia, who are not receiving hydroxyurea (HU) and in adult SCA patients who are receiving a stable dose of HU Secondary Objectives: To characterise the pharmacokinetic (PK) profile of IMR-687 in adult patients with SCA who are/are not receiving a stable dose of HU To characterise the PK profile of HU in adult patients with SCA before and after receiving IMR-687 to determine if there is a clinically relevant PK interaction. Exploratory Objectives: To assess the pharmacodynamic (PD) effects of IMR-687 in adult patients with SCA who are/are not receiving stable HU To assess the potential efficacy of IMR-687 on SCA-related clinical outcome measures in adult patients with SCA who are/are not receiving stable HU
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Blood - Sickle Cell Disease
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Check with study contact
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Jennifer (Chih-Chen) Wong. Telephone: Not Available. Email: cwong@uchc.edu or Sasia-Marie Jones. Telephone: Not available. Email: sajones@uchc.edu
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Enrolling/recruiting. For current recruitment status, please check with study contact.
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