First-in-Human Study of BCX9930 in Healthy Volunteers and Patients With PNH

NCT04330534 | Completed Phase 1 DMC

• 1 other identifier: BCX9930-101
• Study Type: interventional
• Target: 168
• Locations: 3 countries
• Sites: 4

Brief Summary

This is a 3-part Phase 1 dose-ranging study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single (Part 1) and multiple (Part 2) ascending doses of BCX9930 in healthy subjects and in subjects with paroxysmal nocturnal hemoglobinuria (PNH; Part 3). Pharmacokinetics is an analysis of how the body handles the study drug BCX9930 and pharmacodynamics is an analysis of the activity that the study drug BCX9930 may have in the body.

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Keywords

Paroxysmal Nocturnal Hemoglobinuria; first-in-human; Factor D; complement inhibitor; alternative pathway inhibitor; BioCryst; proof-of-concept

Outcome Measures

Primary Outcomes (37)

• Incidence of graded treatment-emergent adverse events

  Part 1: Day 16

• Incidence of graded treatment-emergent adverse events

  Part 2: Day 23 (cohorts with 3 and 7 day dosing duration) or Day 31 (cohorts with 14 day dosing duration)

• Incidence of graded treatment-emergent adverse events

  Part 3:Day 44 or Week 50 (South Africa only)

• Incidence of graded laboratory chemistry abnormalities

  Part 1: Day 16

• Incidence of graded laboratory chemistry abnormalities

  Part 2: Day 23 (cohorts with 3 and 7 day dosing duration) or Day 31 (cohorts with 14 day dosing duration)

• Incidence of graded laboratory chemistry abnormalities

  Part 3:Day 44 or Week 50 (South Africa only)

• Incidence of graded urinalysis abnormalities

  Part 1: Day 16

• Incidence of graded urinalysis abnormalities

  Part 2: Day 23 (cohorts with 3 and 7 day dosing duration) or Day 31 (cohorts with 14 day dosing duration)

• Incidence of graded urinalysis abnormalities

  Part 3: Day 44 or Week 50 (South Africa only)

• Incidence of graded coagulation abnormalities

  Part 1: Day 16

• Incidence of graded coagulation abnormalities

  Part 2: Day 23 (cohorts with 3 and 7 day dosing duration) or Day 31 (cohorts with 14 day dosing duration)

• Incidence of graded coagulation abnormalities

  Part 3: Day 44 or Week 50 (South Africa only)

• Incidence of graded hematology abnormalities

  Part 1: Day 16

• Incidence of graded hematology abnormalities

  Part 2: Day 23 (cohorts with 3 and 7 day dosing duration) or Day 31 (cohorts with 14 day dosing duration)

• Incidence of graded hematology abnormalities

  Part 3: Day 44 or Week 50 (South Africa only)

• Change from baseline in blood pressure

  Part 1: Day 16

• Change from baseline in blood pressure

  Part 2: Day 23 (cohorts with 3 and 7 day dosing duration) or Day 31 (cohorts with 14 day dosing duration)

• Change from baseline in blood pressure

  Part 3: Day 44 or Week 50 (South Africa only)

• Change from baseline in temperature

  Part 1: Day 16

• Change from baseline in temperature

  Part 2: Day 23 (cohorts with 3 and 7 day dosing duration) or Day 31 (cohorts with 14 day dosing duration)

• Change from baseline in temperature

  Part 3: Day 44 or Week 50 (South Africa only)

• Change from baseline in heart rate

  Part 1: Day 16

• Change from baseline in heart rate

  Part 2: Day 23 (cohorts with 3 and 7 day dosing duration) or Day 31 (cohorts with 14 day dosing duration)

• Change from baseline in heart rate

  Part 3: Day 44 or Week 50 (South Africa only)

• Change from baseline in respiratory rate

  Part 3: Day 44 or Week 50 (South Africa only)

• Change in Electrocardiogram (PR interval)

  Part 1: Day 16

• Change in Electrocardiogram (PR interval)

  Part 2: Day 23 (cohorts with 3 and 7 day dosing duration) or Day 31 (cohorts with 14 day dosing duration)

• Change in Electrocardiogram (PR interval)

  Part 3: Day 44 or Week 50 (South Africa only)

• Change in Electrocardiogram (QRS interval)

  Part 1: Day 16

• Change in Electrocardiogram (QRS interval)

  Part 2: Day 23 (cohorts with 3 and 7 day dosing duration) or Day 31 (cohorts with 14 day dosing duration)

• Change in Electrocardiogram (QRS interval)

  Part 3: Day 44 or Week 50 (South Africa only)

• Change in Electrocardiogram (RR interval)

  Part 1: Day 16

• Change in Electrocardiogram (RR interval)

  Part 2: Day 23 (cohorts with 3 and 7 day dosing duration) or Day 31 (cohorts with 14 day dosing duration)

• Change in Electrocardiogram (RR interval)

  Part 3:Day 44 or Week 50 (South Africa only)

• Change in Electrocardiogram (QT interval)

  Part 1: Day 16

• Change in Electrocardiogram (QT interval)

  Part 2: Day 23 (cohorts with 3 and 7 day dosing duration) or Day 31 (cohorts with 14 day dosing duration)

• Change in Electrocardiogram (QT interval)

  Part 3:Day 44 or Week 50 (South Africa only)

Secondary Outcomes (12)

• Plasma BCX9930 Cmax

  plasma PK parameters are based on blood sampling through Day 4 for Part 1; through Day 6, 14 or 18 for Part 2 (Day depends on dosing duration); and through Day 28 for Part 3

• Plasma BCX9930 Tmax

  plasma PK parameters are based on blood sampling through Day 4 for Part 1; through Day 6, 14 or 18 for Part 2 (Day depends on dosing duration); and through Day 28 for Part 3

• Plasma BCX9930 AUCinf

  plasma PK parameters are based on blood sampling through Day 4 for Part 1

• Plasma BCX9930 t1/2

  plasma PK parameters are based on blood sampling through Day 4 for Part 1; through Day 6, 14 or 18 for Part 2 (Day depends on dosing duration); and through Day 28 for Part 3

• Plasma BCX9930 AUCtau

  plasma PK parameters are based on blood sampling through Day 6, 14 or 18 for Part 2 (Day depends on dosing duration); and through Day 28 for Part 3

Study Arms (2)

BCX9930

EXPERIMENTAL

Parts 1, 2 and 3

Drug: BCX9930

Placebo

PLACEBO COMPARATOR

Parts 1 and 2 only

Drug: Placebo

Interventions

BCX9930 DRUG

BCX9930 capsules for oral administration

BCX9930

Placebo DRUG

placebo to match BCX9930 capsules for oral administration

Placebo

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide written informed consent
• Acceptable birth control measures for male subjects and women of childbearing potential
• Is expected to adequately comply with required study procedures and restrictions
• Body mass index (BMI) of 18.0 to 32.0 kg/m2.
• Males and non-pregnant, non-lactating females age 18 to 55 years.
• Part 2: Must have recent vaccination against Neisseria meningitidis and must be negative for colonisation by Neisseria meningitidis
• Male or non-pregnant, non-lactating female subjects ≥ 18 years old
• Have been diagnosed with PNH and have laboratory values indicative of active PNH
• Subjects naïve to both eculizumab and ravulizumab treatment, who have no access to, or are considered unsuitable for proven effective alternative options as per the local standard of care OR subjects currently receiving treatment with eculizumab or ravulizumab have been on a stable dose of eculizumab or ravulizumab for 6 months
• Must have recent vaccination against Neisseria meningitidis

You may not qualify if:

• Clinically significant medical history, current medical or psychiatric condition that, in the opinion of the Investigator or Sponsor, would interfere with the subject's ability to participate in the study or increase the risk of participation for that subject.
• Clinically significant ECG finding or laboratory/urinalysis abnormality
• Use of prescription or over the counter medication within 14 days of dosing
• Participation in any other investigational drug study within 90 days of screening
• Recent or current history of alcohol or drug abuse within the last 12 months
• Current smokers and those who have smoked within the last 12 months
• Positive serology for HIV or active infection with HBV or HCV
• Pregnant or nursing
• Donation or loss of greater than 400 mL of blood within 3 months
• History of severe hypersensitivity to any drug or Neisseria meningitidis vaccines (Part 2)
• Subject has recently received a live attenuated vaccine within 30 days of dosing or another type of vaccine within 14 days of Day 1
• Apart from a diagnosis of PNH, any clinically significant medical or psychiatric condition or medical history, other than those associated with PNH disease, that, in the opinion of the Investigator or Sponsor, would interfere with the subject's ability to participate in the study or participation would increase the risk for that subject
• Active bacterial infection
• Hereditary complement deficiency
• History of hematopoietic stem cell /marrow transplantation

Sponsors & Collaborators

• BioCryst Pharmaceuticals: lead

Study Sites (4)

Study Site

Vienna, Austria

Location

Study Site

Bloemfontein, South Africa

Location

Study Site

Pretoria, South Africa

Location

Study Site

London, United Kingdom

Location

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Study Officials

• Antionio Risitano

  University of Naples

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Part 3 is not masked; Parts 1 and 2 are participant and investigator masked.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Each cohort in Part 3 is enrolled as a single group; Parts 1 and 2 follow a parallel study model.

Study Record Dates

• First Submitted: March 23, 2020
• First Posted: April 1, 2020
• Study Start: March 3, 2020
• Primary Completion: November 11, 2020
• Study Completion: January 25, 2021
• Last Updated: February 17, 2022

Record last verified: 2022-02

Locations

ZA (2); GB (1); AU (1)