ASH Clinical News Focus on Rare Diseases

CLINICAL TRIAL UPDATES estimated study completion date: September 2018 recruiting participants estimated enrollment: 225 sponsor: Onconova Therapeutics, Inc. Patients with myelodysplastic syndromes (MDS) for whom the hypomethylating agents (HMA) azacitidine or decitabine have a poor prognosis have limited treatment options. In a previous study, ONTIME, the multikinase inhibitor rigosertib did not improve survival, compared with conventional care, for patients with MDS for whom the HMAs azacitidine or decitabine fail. However, patients who were primary-refractory to HMAs seemed to fare better. The INSPIRE study has a similar design to the ONTIME trial, but it enriches for higher-risk patients with no or transient responses to HMAs. study status: Currently CLOTTING AND BLEEDING DISORDERS A Phase 2, Open Label, Randomized, Dose Ranging, Safety, Efficacy, Pharmacokinetic and Pharmacodynamic Study of AG-348 in Adult Patients With Pyruvate Kinase Deficiency (NCT02476916) study design: Phase II, open-label, randomized, multicenter, doseranging safety/efficacy study study start date: June 2015 estimated study completion date: March 2017 study status: Currently recruiting participants estimated enrollment: 75 sponsor: Agios Pharmaceuticals, Inc. The study will evaluate the safety and tolerability of multiple doses of AG-348, a novel, first-in-class, oral activator of the pyruvate kinase enzyme, as well as the drug’s pharmacokinetic (PK) and pharmacodynamic (PD) profile. Investigators also hope to identify early indicators of clinical efficacy. Adult patients with pyruvate kinase deficiency will receive multiple doses of AG-348 – for up to 24 weeks and for an extension period of up to two additional years. A Phase III Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Prophylactic Emicizumab Versus No Prophylaxis in Hemophilia A Patients With Inhibitors (NCT02622321) study design: Randomized, open-label, parallel assignment safety/ efficacy study study start date: November 2015 estimated study completion date: January 2018 study status: Currently recruiting participants estimated enrollment: 70 sponsor: Hoffmann-La Roche Emicizumab, or ACE910, the first-in-class factor VIIIa-mimetic bispecific antibody, was previously granted breakthrough therapy designation for the prophylactic treatment of patients with hemophilia A with factor VIII inhibitors. This multicenter study will further evaluate the safety, efficacy, and PK of prophylactic emicizumab in patients previously treated with episodic or prophylactic bypassing agents. 14 Focus on Rare DIseases A Phase I Single-Ascending and Multiple-Ascending Dose, Safety, Tolerability, and Pharmacokinetics Study of Subcutaneously Administered ALN-AT3SC in Healthy Adult Volunteers and Hemophilia A or B Patients (Moderate or Severe Hemophilia) (NCT02035605) study design: Randomized, single-blind, parallel assignment safety study study start date: January 2014 estimated study completion date: April 2017 study status: Currently recruiting participants estimated enrollment: 72 sponsor: Alnylam Pharmaceuticals ALN-AT3SC works by reducing the liver’s production of the antithrombin protein, which plays a role in preventing blood from clotting. In previous animal research, ALN-AT3SC led to lower amounts of antithrombin protein in the blood; this first-in-human study will investigate whether single doses of ALN-AT3SC, administered subcutaneously, are safe in healthy volunteers and if multiple doses of ALN-AT3SC are safe in patients with hemophilia. LEUKEMIA A Phase II Clinical Trial of Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin for CD25 Positive Hairy Cell Leukemia (NCT00321555) study design: Open-label, phase II safety/efficacy study study start date: April 2006 estimated study completion date: March 2019 study status: Currently recruiting participants estimated enrollment: 27 sponsor: National Cancer Institute Approximately 80 percent of patients with hairy cell leukemia (HCL) have malignant cells that express CD25 (Tac or IL2Ra). The experimental drug LMB-2 is a recombinant immunotoxin that has been shown to kill leukemia and lymphoma cells with the CD25 protein. The purpose of this study is to determine the activity of anti-Tac(Fv)-PE38 (LMB-2) in patients with CD25-expressing HCL. The study will assess response rate, response duration, LMB-2 immunogenicity, PK, toxicity, and monitor soluble Tac levels in the serum. Randomized Phase II Trial of Rituximab With Either Pentostatin or Bendamustine for Multiply Relapsed or Refractory Hairy Cell Leukemia (NCT01059786) study design: Randomized, crossover, open-label, phase II efficacy study study start date: December 2009 estimated study completion date: December 2017 study status: Currently recruiting participants estimated enrollment: 74 sponsor: National Cancer Institute By combining rituximab with other anti-cancer drugs, investigators hope to improve outcomes for patients with hairy cell leukemia (HCL) whose disease has not responded well to or has recurred after standard therapies. This trial will help determine if pentostatin or bendamustine, when added to rituximab, could be a more effective treatment for HCL than rituximab alone.

ASH Clinical News Focus on Rare Diseases | Page 16