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

NCT04247594 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: GBT440-029C5341042
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 6

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

Conditions

Sickle Cell Disease

Keywords

Sickle Cell Disease, SCD

Outcome Measures

Primary Outcomes (1)

• Treatment-emergent Adverse Events (AEs)

  Treatment emergent AEs including SAEs

  approximately 300 days

Secondary Outcomes (3)

• Number of Participants With Clinically Significant Abnormalities in Hb, Unconjugated Bilirubin, % Reticulocyte, Absolute Reticulocyte, and Lactate Dehydrogenase [LDH]

  approximately 200 days

• Number of Participants With an Hb Increase > 1 g/dL Compared to Baseline

  approximately 200 days

• Incidence Rate of VOCs

  approximately 200 days

Study Arms (4)

Period 1

EXPERIMENTAL

1500 mg per day

Drug: Voxelotor

Period 2

EXPERIMENTAL

2000 mg per day

Drug: Voxelotor

Period 3

EXPERIMENTAL

2500 mg per day

Drug: Voxelotor

Period 4

EXPERIMENTAL

3000 mg per day

Drug: Voxelotor

Interventions

Voxelotor DRUG

synthetic small molecule supplied as 500 mg tablets

Period 1; Period 2; Period 3; Period 4

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female with SCD
• Documentation of SCD genotype HbSS or HbSB0
• Age 18 to \< 60 years, inclusive
• Hemoglobin ≥ 5.5 and ≤ 10.5 g/dL during Screening, and considered stable and close to Baseline by the Investigator
• 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.
• 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

You may not qualify if:

• More than 10 VOCs within 12 months of screening that required a hospital, emergency room, or clinic visit
• Female participant who is breast feeding or pregnant
• 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
• 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)
• Screening laboratory test of alanine aminotransferase (ALT) \> 4 × upper level of normal (ULN)
• Clinically significant bacterial, fungal, parasitic, or viral infection which requires therapy, including acute bacterial infection requiring antibiotics
• Known to be COVID-19 positive from within 3 weeks of screening through Day 1
• Participants with active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive
• 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
• 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:
• Unstable angina pectoris or myocardial infarction or elective coronary intervention
• Congestive heart failure requiring hospitalization
• Uncontrolled clinically significant arrhythmias
• Pulmonary hypertension

Sponsors & Collaborators

• Pfizer: lead

Study Sites (6)

Guy's and St Thomas' NHS Foundation Trust

London, United Kingdom

Location

Guy's Hospital

London, United Kingdom

Location

Hammersmith Hospital

London, United Kingdom

Location

Homerton University

London, United Kingdom

Location

King's College Hospital

London, United Kingdom

Location

Royal London Hospital, Barts Health NHS Trust

London, United Kingdom

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

voxelotor

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Eleanor Lisbon
• Organization: Global Blood Therapeutics, Inc.

elisbon@gbt.com

+1 913 449 4319

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2020
• First Posted: January 30, 2020
• Study Start: January 9, 2020
• Primary Completion: June 8, 2021
• Study Completion: June 8, 2021
• Last Updated: November 21, 2023
• Results First Posted: November 21, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share

Locations

GB (6)