A Study to Evaluate GBT021601-012 Single Dose and Multiple Dose in Participants With Sickle Cell Disease (SCD)

NCT04983264 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: GBT021601-012C5351002
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK), and pharmacodynamics (i.e., how the body absorbs, distributes, breaks down, and excretes) of GBT021601, a hemoglobin S (HbS) polymerization inhibitor, in participants with SCD, following single and multiple ascending doses.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  An adverse event (AE) was any untoward medical occurrence in a study participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. A treatment-emergent AE (TEAE) was an AE that occurs or worsens during the on-treatment period defined as the time from the first dose of study drug through minimum of 56 days after last dose of study treatment. A Serious Adverse Event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life-threatening experience (immediate risk of death); required inpatient hospitalization or prolongation if existing hospitalization; resulted in persistent or significant disability/ incapacity; resulted in congenital anomaly/birth defect; was considered an important medical event. TEAEs and SAEs were reported for both Sickle Cell Disease (SCD) and non-SCD related events, in this outcome measure.

  From first dose of study drug (Day 1) to at least 56 days after last dose of study drug (up to a maximum of 316 days)

• Number of Participants With Clinically Significant Physical Examination Findings

  Physical examination included were general appearance, head, ears, eyes, nose, throat, neck, skin, cardiovascular system, respiratory system, gastrointestinal system, musculoskeletal system, lymph nodes, and nervous system. Clinically significant physical examination abnormalities were considered as adverse events based on investigator's discretion.

  Baseline (Day 1) up to at least 56 days after last dose of study drug (up to a maximum of 316 days)

• Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters

  Laboratory parameters included hematology(hemoglobin,hematocrit,red blood cell count,platelet count,white blood cell count,total neutrophils,eosinophils,monocytes,basophils,lymphocytes);blood chemistry(blood urea,nitrogen, creatinine,glucose,calcium,sodium,potassium,chloride,total bicarbonate,aspartate aminotransferase,alanine aminotransferase,total bilirubin,alkaline phosphatase,uric acid albumin,total protein);urinalysis(decimal logarithm of reciprocal of hydrogen ion activity \[pH\], glucose, protein, blood,ketones, microscopy\[urine tested positive for blood or protein\]),urine drug screening:cannabinoids,amphetamines,methamphetamines,opiates,methadone,cocaine,benzodiazepines,phencyclidine,barbiturates,alcohol breath test. Hemoximetry RBC deformability,dense cells test; erythropoietin,follicle stimulating hormone,pregnancy test,Serology panel for HIV 1/2 antibody,Hepatitis A, B and C,SARS CoV-2.Clinical significance of any parameter was determined at the investigator's discretion.

  Baseline (Day 1) up to at least 56 days after last dose of study drug (up to a maximum of 316 days)

• Number of Participants With Clinically Significant Change From Baseline in Vital Signs

  Vital signs assessments included were systolic and diastolic blood pressure, heart rate, respiratory rate and body temperature. These measurements were taken after the participants had rested for at least 5 minutes in the supine position. Any clinically significant abnormal vital sign assessment required at least one repeat measurement. Clinical significance of any parameter was determined based on investigator's discretion.

  Baseline (Day 1) up to at least 56 days after last dose of study drug (up to a maximum of 316 days)

• Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG)

  ECG values included here were Heart rate (HR), PR, QRS, QT, and QTcF intervals, interpretation of the tracings (eg, rhythm, presence of arrhythmia or conduction defects, any evidence of myocardial ischemia/infarction, or ST segment, T-wave, and U-wave abnormalities). Abnormal and clinically significant 12-lead ECG included QT interval corrected for heart rate according to Fridericia's formula (QTcF) \> 450 millisecond (ms), QRS interval \>= 120 ms, PR interval \> 220 ms, based on the average of triplicated ECG, assessed at Screening and Day-1. If any of these test results were out of range, then the test could be repeated once (in triplicate).

  Baseline (Day 1) up to at least 56 days after last dose of study drug (up to a maximum of 316 days)

Secondary Outcomes (22)

• Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A

  Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 168 hrs, 336 hrs, 504 hrs, 672 hrs, 1008 hrs post-dose on Day 1

• Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B

  Pre-dose, 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 56, 63, 70, 77, 84, 91, 98, 105, 112

• Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part C

  Pre-dose on Day 1, 14, 28, 42 and 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 28 and 42

• Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B

  Pre-dose, 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 56, 63, 70, 77, 84, 91, 98, 105, 112

• Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part C

  Pre-dose on Day 1, 14, 28, 42 and 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 28 and 42

Study Arms (2)

Single-dose Period (Part A)

EXPERIMENTAL

Refer to Study Description

Drug: GBT021601

Multiple Ascending-dose Period (Part B and Part C)

EXPERIMENTAL

Refer to Study Description

Drug: GBT021601

Interventions

GBT021601 DRUG

Tablets and capsules which contain GBT021601 drug substance

Multiple Ascending-dose Period (Part B and Part C); Single-dose Period (Part A)

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
• Participants with SCD ages 18 to 60 years, inclusive.
• Participant has provided documented informed consent.
• Patients with stable and close to baseline hemoglobin value
• Patients on HU should be on stable dose for at least 90 days prior to signing ICF

You may not qualify if:

• Patients had more than 10 VOC within 12 months of screening
• Patients who are pregnant or nursing
• Patients who receive RBC transfusion therapy regularly or received an RBC transfusion for any reason within 60 days of signing the ICF
• Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of signing the ICF or within 24 days prior to Day 1 treatment

Sponsors & Collaborators

• Pfizer: lead

Study Sites (3)

Advanced Pharma CR, LLC

Miami, Florida, 33147, United States

Location

Visionaries Clinical Research LLC

Atlanta, Georgia, 30329, United States

Location

Children's Healthcare of Atlanta AFLAC Center

Atlanta, Georgia, 30342, United States

Location

Related Links

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

MeSH Terms

Conditions

Anemia, Sickle Cell

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: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2021
• First Posted: July 30, 2021
• Study Start: May 21, 2021
• Primary Completion: December 6, 2022
• Study Completion: December 6, 2022
• Last Updated: June 10, 2024
• Results First Posted: June 10, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)