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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. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04247594
Recruitment Status : Terminated (Data will not inform further development of Voxelotor)
First Posted : January 30, 2020
Last Update Posted : September 1, 2022
Information provided by (Responsible Party):
Global Blood Therapeutics

Brief Summary:
Study participants will undergo up to four periods of voxelotor administered orally at progressively higher dose levels from 1500 mg until either a maximum tolerated dose (MTD) or 3000 mg/day dose is reached, whichever occurs first

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: N/A
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
Actual Primary Completion Date : June 8, 2021
Actual Study Completion Date : June 8, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Voxelotor

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

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

  3. Incidence rate of VOCs [ Time Frame: approximately 200 days ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

Inclusion Criteria:

  1. Male or female with SCD
  2. Documentation of SCD genotype HbSS or HbSB0
  3. Age 18 to < 60 years, inclusive
  4. Hemoglobin ≥ 5.5 and ≤ 10.5 g/dL during Screening, and considered stable and close to Baseline by the Investigator
  5. For participants taking HU, the dose in mg/kg must be stable for at least 90 days prior to signing the informed consent form (ICF) and with no anticipated need for dose adjustments during the study, in the opinion of the Investigator.
  6. 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
  7. Participant has provided documented informed consent

Exclusion Criteria:

  1. More than 10 VOCs within 12 months of screening that required a hospital, emergency room, or clinic visit
  2. Female participant who is breast feeding or pregnant
  3. Receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) or have received an RBC transfusion for any reason within 60 days of signing the ICF or at any time during the Screening Period
  4. Hospitalized for sickle cell crisis or other vaso-occlusive event within 30 days prior to dosing (ie, a vaso-occlusive event cannot be within 30 days prior to dosing)
  5. Screening laboratory test of alanine aminotransferase (ALT) > 4 × upper level of normal (ULN)
  6. Clinically significant bacterial, fungal, parasitic, or viral infection which requires therapy, including acute bacterial infection requiring antibiotics
  7. Known to be COVID-19 positive from within 3 weeks of screening through Day 1
  8. Participants with active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive
  9. Severe renal dysfunction (estimated glomerular filtration rate < 30 mL/min/1.73 m2 at the Screening visit; calculated by the local laboratory to assess safety) or is on chronic dialysis
  10. 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)
  11. History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:

    1. Unstable angina pectoris or myocardial infarction or elective coronary intervention
    2. Congestive heart failure requiring hospitalization
    3. Uncontrolled clinically significant arrhythmias
    4. Pulmonary hypertension
  12. Criteria related to ECG parameters:

    1. PR interval > 220 msec in any participant
    2. QRS interval > 120 msec or QT interval corrected using Fridericia's formula (QTcF) > 480 msec (both genders) in participants without bundle branch block
    3. QRS interval > 120 msec in participants with newly (within 3 months) emerged bundle branch block
    4. A participant with stable bundle branch block with or without stable cardiac disease may be enrolled; QRS interval > 120 msec and QTcF interval > 480 msec are acceptable in these participants.
  13. Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable)
  14. 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
  15. Inadequate venous access as determined by the Investigator/site staff
  16. Medical, psychological, or behavioral conditions, which, in the opinion of the Investigator, may preclude safe participation, confound study interpretation, interfere with compliance, or preclude informed consent
  17. Received erythropoietin or other hematopoietic growth factor treatment within 28 days of signing ICF or is anticipated to require such agents during the study
  18. Ongoing or recent (within 2 years) substance abuse
  19. Known allergy to voxelotor
  20. Use of herbal medications (eg, St. John's Wort), sensitive cytochrome P450 (CYP) 3A4 substrates with a narrow therapeutic index, strong CYP3A4 inhibitors, fluconazole, or moderate or strong CYP3A4 inducers

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

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United Kingdom
Guy's and St Thomas' NHS Foundation Trust
London, United Kingdom
Guy's Hospital
London, United Kingdom
Hammersmith Hospital
London, United Kingdom
Homerton University
London, United Kingdom
King's College Hospital
London, United Kingdom
Royal London Hospital, Barts Health NHS Trust
London, United Kingdom
Sponsors and Collaborators
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: September 1, 2022
Last Verified: August 2022

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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
Hematologic Diseases
Genetic Diseases, Inborn