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

• Sponsor: Global Blood Therapeutics (Industry)
• Overall Status: Unknown status
• CT.gov ID: NCT04247594
• Collaborator: (none)
• Enrollment: 45
• Locations: 6
• Arms: 2
• Anticipated Duration (Months): 22.7
• Patients Per Site: 7.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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

1. 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

Study Design

• Study Type: Interventional
• Anticipated 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: Jan 9, 2020
• Anticipated Primary Completion Date: Jun 1, 2021
• Anticipated Study Completion Date: Dec 1, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Treatment-emergent AEs [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 [approximately 200 days]

   Change in Hb

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

   participants with an Hb increase > 1 g/dL compared to Baseline

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Guy's and St Thomas' NHS Foundation Trust	London		United Kingdom
2	Guy's Hospital	London		United Kingdom
3	Hammersmith Hospital	London		United Kingdom
4	Homerton University	London		United Kingdom
5	King's College Hospital	London		United Kingdom
6	Royal London Hospital, Barts Health NHS Trust	London		United Kingdom

Sponsors and Collaborators

• Global Blood Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Global Blood Therapeutics
• ClinicalTrials.gov Identifier: NCT04247594
• Other Study ID Numbers: GBT440-029
• First Posted: Jan 30, 2020
• Last Update Posted: Mar 16, 2020
• Last Verified: Mar 1, 2020

• 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: Anemia, Sickle Cell

Study Results

No Results Posted as of Mar 16, 2020