Clinical trial NCT04983264: A Study to Evaluate GBT021601-012 Single Dose and Multiple Dose in Participants With Sickle Cell Disease (SCD)
Official title: An Intrapatient Single Dose and Multiple Ascending Dose Study to Evaluate the Pharmacokinetics, Safety, Tolerability, and Pharmacodynamics of GBT021601, a Hemoglobin S Polymerization Inhibitor, in Participants With Sickle Cell Disease (SCD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Sickle Cell Disease
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-07-30
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: This is an open-label intrapatient single dose followed by a multiple dose escalation study in at least six (6) participants with SCD.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: 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)
measure: Number of Participants With Clinically Significant Physical Examination Findings
timeFrame: Baseline (Day 1) up to at least 56 days after last dose of study drug (up to a maximum of 316 days)
measure: Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters
timeFrame: Baseline (Day 1) up to at least 56 days after last dose of study drug (up to a maximum of 316 days)
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: Baseline (Day 1) up to at least 56 days after last dose of study drug (up to a maximum of 316 days)
measure: Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG)
timeFrame: Baseline (Day 1) up to at least 56 days after last dose of study drug (up to a maximum of 316 days)
Secondary outcomes:
measure: Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A
timeFrame: 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
measure: Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B
timeFrame: 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
measure: Maximum GBT021601 Concentration (Cmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part C
timeFrame: 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
measure: Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part B
timeFrame: 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
measure: Minimum GBT021601 Concentration (Cmin) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part C
timeFrame: 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
measure: Time to Attain Maximum Serum Concentration (Tmax) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A
timeFrame: 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
measure: Area Under the Concentration Time Curve From Time Zero to the Next Dose (AUC0-tau) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A
timeFrame: 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
measure: Area Under the Serum Concentration Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A
timeFrame: 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
measure: Area Under the Concentration Time Curve From Time Zero up to Time 24 Hours (AUC 0-24) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A
timeFrame: Pre-dose, 0.25 hour (hr), 0.5 hr, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs,12 hrs, 24 hrs post-dose on Day 1
measure: Apparent Oral Clearance (CL/F) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A
timeFrame: 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
measure: Terminal Elimination Half-Life (t1/2) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A
timeFrame: 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
measure: Apparent Volume of Distribution (Vz/F) in Plasma, Whole Blood and Red Blood Cells (RBCs): Part A
timeFrame: 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
measure: Percentage Hemoglobin Occupancy
timeFrame: Part A: Pre-dose,0.25,0.5,1,2,4, 6,8,12,24,36,48,72,168,336,504,672,1008 hrs on Day 1; Part B: Pre-dose,0.25 to 1,2 to 4 hrs post-dose on Day 56,63,70,77,84,91,98,105,112; Part C:Pre-dose on Day 1,14,28,42 and 0.25 to 1, 2 to 4 hrs post-dose on Day 28,42
measure: Plasma Concentrations Versus Time Summary of GBT021601: Part A
timeFrame: 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
measure: Plasma Concentrations Versus Time Summary of GBT021601: Part B
timeFrame: 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, 140,168, 196, 218
measure: Plasma Concentrations Versus Time Summary of GBT021601: Part C
timeFrame: Pre-dose on Day 1, 14, 28, 42 and 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 28, 42, 70, 98
measure: Whole Blood Concentrations Versus Time Summary of GBT021601: Part A
timeFrame: 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
measure: Whole Blood Concentrations Versus Time Summary of GBT021601: Part B
timeFrame: 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, 140,168, 196, 218
measure: Whole Blood Concentrations Versus Time Summary of GBT021601: Part C
timeFrame: Pre-dose on Day 1, 14, 28, 42 and 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 28, 42, 70, 98
measure: Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part A
timeFrame: 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
measure: Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part B
timeFrame: 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, 140,168, 196, 218
measure: Red Blood Cell Concentrations Versus Time Summary of GBT021601: Part C
timeFrame: Pre-dose on Day 1, 14, 28, 42 and 0.25 hr to 1 hr, 2 to 4 hrs post-dose on Day 28, 42, 70, 98
Other outcomes:
Locations:
city: Miami
country: United States
facility: Advanced Pharma CR, LLC
state: Florida
city: Atlanta
country: United States
facility: Visionaries Clinical Research LLC
state: Georgia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta AFLAC Center
state: Georgia
Study officials:
affiliation: Pfizer
name: Pfizer Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: