Clinical Trials in Healthy Volunteers
HemaQuest completed two Phase 1 dose escalation trials of HQK-1001 in healthy volunteers. The objectives of these trials were to evaluate the safety and pharmacokinetics of HQK-1001. In the initial trial, 32 healthy volunteers were administered single oral doses of HQK-1001 (or placebo) at doses ranging from 2 to 20 mg/kg. All dose levels were well-tolerated, and there was no difference in the number or severity of side effects between HQK-1001 and placebo.
In a subsequent trial, HQK-1001 (or a placebo) was administered to healthy volunteers at doses of 5, 10 and 15 mg/kg given orally once daily for 14 days. In this trial, HQK-1001 given daily for 14 days was also found to be well-tolerated, with no difference in side effects between those receiving placebo and HQK-1001. In addition, the trial demonstrated pharmacodynamic effects documented by increases in reticulocytes, a measure of red blood cell production. Plasma drug concentrations within the therapeutic range (as demonstrated in laboratory studies) were achieved in subjects receiving HQK-1001 at doses of 10 and 15 mg/kg.
Proof of Concept Clinical Trials in Patients with Genetic Hemoglobin Disorders
HemaQuest has completed two clinical trials of HQK-1001 in patients with genetic hemoglobin disorders, one in patients with sickle cell disease and one in patients with beta thalassemia.
Clinical Trial in Sickle Cell Disease (Protocol HQP-2008-004)
Number and Title: HQP-2008-004: A Randomized, Blinded, Placebo-controlled, Dose Escalation Trial to Evaluate the Safety, Tolerability and Pharmacokinetics of HQK 1001 in Subjects with Sickle Cell Disease
This placebo-controlled study was designed to evaluate the safety, pharmacokinetics (i.e., study of drug concentrations in the blood over time), and effect on laboratory markers of HKQ-1001 taken at doses of 10, 20, and 30 mg/kg (or placebo) once daily for two 6-week cycles in patients with sickle cell disease. Patients were eligible for enrollment if they were between the age of 12 and 60 years, had moderately severe sickle cell disease, and a baseline fetal hemoglobin (HbF) of at least 2%. More information about the study design can be found at www.clinicaltrials.gov.
Preliminary results of the study were presented at the 2010 Annual Meeting of the American Society of Hematology. Additional information can be found at ASH 2010 - SCD.
A total of 24 patients were enrolled in the study. HQK-1001 was well-tolerated with no significant drug-related adverse events. Increases in HbF levels were observed at all dose levels, with the highest effects observed at 30 mg/kg, where 5 of 7 treated patients responded with a mean peak increase of 2.6% HbF above baseline. HbF increased both in patients who did, or who did not, take concomitant hydroxyurea. A mean peak increase in total hemoglobin of 1.3 g/dL (range 0.9 to 2.4 g/dL) above baseline was also observed in patients administered HQK-1001. These promising results led to the development of a subsequent study to evaluate higher dose of HQK-1001 and longer duration of drug administration.
For information about this trial email: info@hemaquest.com.
More information can be found at www.clinicaltrials.gov.
Clinical Trial in Beta Thalassemia (Protocol HQP-2008-003b)
Number and Title: HQP-2008-003b: A Multi-National, Blinded, Placebo-Controlled, Dose Escalation Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of HQK-1001 in Subjects with Beta Thalassemia Intermedia, including Hemoglobin E Beta Thalassemia
This placebo-controlled study was designed to evaluate the safety, pharmacokinetics, and effects on biologic markers of HQK-1001 taken at doses of 10, 20, 30 and 40 mg/kg (or placebo) orally daily for 8 weeks in patients with thalassemia intermedia or hemoglobin E beta thalassemia. Patients were eligible for enrollment if they were between the age of 12 and 60 years, had beta-thalassemia intermedia, and a baseline fetal hemoglobin (HbF) of at least 2%. More information can be found at www.clinicaltrials.gov.
Preliminary results of the study were presented at the 2010 Annual Meeting of the American Society of Hematology. Additional information can be found at ASH 2010 - Thalassemia.
A total of 21 patients were enrolled in the study. HQK-1001 was well-tolerated with no significant drug-related adverse events. Increase in HbF was observed in all HQK-1001 dose groups, with best results observed at the dose of 20 mg/kg, both in patients who did, or who did not, take concomitant hydroxyurea. These promising results led to the development of a subsequent study to evaluate higher dose of HQK-1001 and longer duration of drug administration.
For information about this trial email: info@hemaquest.com.
More information can be found at www.clinicaltrials.gov.
Phase 2 Trial in Patients with Sickle cell Disease (Protocol HQP-1001-SCD-006)
Number and Title: HQP-1001-SCD-006: A Randomized, Open-Label, Multi-Dose Study of HQK 1001 in Patients with Sickle Cell Disease
Interim Results Presented at ASH 2011
In April 2011, HemaQuest initiated a multicenter Phase 2 clinical trial to evaluate HQK-1001 taken orally at higher doses (30, 40, and 50 mg/kg daily) and for longer duration (up to 6 months) than previously evaluated. Patient enrollment in the study was completed and closed in September 2011 with 52 patients, 12 to 60 years old, with moderate to severe sickle cell disease, whether or not taking hydroxyurea for their disease. The study is being conducted in clinical sites in the US, Canada, Jamaica, Egypt and Lebanon.
For information about this trial email: info@hemaquest.com.
More information can be found at www.clinicaltrials.gov.
Phase 2 Trial in Patients with Beta Thalassemia
In 2011, HemaQuest will support two investigator-sponsored Phase 2 clinical trials to evaluate HQK-1001 taken orally at 20 mg/kg daily for 6 months in patients with moderately severe beta thalassemia. These studies will be conducted at clinical sites in Lebanon and Thailand. For additional information about the study, please email info@hemaquest.com.
For information about this trial email: info@hemaquest.com.
