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Dose Escalation Study to Evaluate the Safety, Tolerability, PK and PD of Voxelotor in Patients With SCD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04247594
Recruitment Status : Recruiting
First Posted : January 30, 2020
Last Update Posted : January 31, 2020
Sponsor:
Information provided by (Responsible Party):
Global Blood Therapeutics

Brief Summary:
This is a dose escalation study to evaluate the safety and tolerability of voxelotor at daily doses of 1500 mg to 3000 mg in participants with sickle cell disease (SCD). The study is designed to include 2 separate cohorts. In Cohort A participants will undergo up to 4 periods of voxelotor administration at progressively higher dose levels from 1500 mg until either a maximum tolerated dose (MTD) or 3000 mg orally daily is reached. Cohort B (following Cohort A) will assess the tolerability and safety of doses higher than 1500 mg administered without up-titration.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: Voxelotor Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open Label, Multiple Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Voxelotor in Patients With Sickle Cell Disease
Actual Study Start Date : January 9, 2020
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort A open label
Participants will receive progressively higher doses of voxelotor administration starting from 1500 mg
Drug: Voxelotor
synthetic small molecule supplied as 500 mg tablets

Experimental: Cohort B open label
Participants will receive doses higher than 1500 mg administered without up-titration
Drug: Voxelotor
synthetic small molecule supplied as 500 mg tablets




Primary Outcome Measures :
  1. Treatment-emergent AEs [ Time Frame: approximately 200 days ]
    Treatment emergent AEs including SAEs


Secondary Outcome Measures :
  1. Change in Hb and clinical measures of hemolysis (unconjugated bilirubin, % reticulocyte, absolute reticulocyte, and lactate dehydrogenase [LDH]) from Baseline [ Time Frame: approximately 200 days ]
    Change in Hb

  2. Proportion of participants with an Hb increase > 1 g/dL compared to Baseline [ Time Frame: approximately 200 days ]
    participants with an Hb increase > 1 g/dL compared to Baseline



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female with sickle cell disease
  • Documentation of SCD genotype HbSS or HbSB0
  • Age 18 to < 60 years, inclusive
  • Participants, who if female and of child bearing potential, agree to use highly effective methods of contraception or practicing abstinence from study start to 30 days after the last dose of study drug, and who if male, agree to use barrier methods of contraception or practice abstinence from study start to 30 days after the last dose of study drug
  • Participant has provided documented informed consent

Exclusion Criteria:

  • More than 10 vaso-occlusive crises (VOCs) within 12 months of screening that required a hospital, emergency room, or clinic visit
  • Female participant who is breast feeding or pregnant
  • Hospitalized for sickle cell crisis or other vaso-occlusive event prior to 30 days of dosing (ie, a vaso-occlusive event cannot be within 30 days prior to dosing)
  • Participants with known active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive
  • Severe renal dysfunction or on chronic dialysis
  • History of malignancy within the past 2 years prior to treatment Day 1 requiring chemotherapy and/or radiation (with the exception of local therapy for non-melanoma skin malignancy)
  • History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:
  • Participated in another clinical trial of an investigational agent or medical device within 30 days or 5 half-lives of date of informed consent, whichever is longer, or is currently participating in another trial of an investigational agent or medical device
  • Inadequate venous access as determined by the Investigator/site staff
  • Ongoing or recent (within 2 years) substance abuse
  • Inability to undergo magnetic resonance imaging (MRI) or cardiopulmonary exercise test (CPET) assessments (Cohort B only)
  • Known allergy to voxelotor

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04247594


Locations
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United Kingdom
Guys and St Thomas' NHS Foundation Trust Recruiting
London, United Kingdom
Contact: Henry Fok, Dr       henry.fok@nhs.net   
Contact    +442071882600      
Sponsors and Collaborators
Global Blood Therapeutics
Investigators
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Study Director: Dan Rudin, MD Global Blood Therapeutics

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Responsible Party: Global Blood Therapeutics
ClinicalTrials.gov Identifier: NCT04247594    
Other Study ID Numbers: GBT440-029
First Posted: January 30, 2020    Key Record Dates
Last Update Posted: January 31, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Global Blood Therapeutics:
Sickle Cell Disease, SCD
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn