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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04330534
Recruitment Status : Completed
First Posted : April 1, 2020
Last Update Posted : February 21, 2021
Sponsor:
Information provided by (Responsible Party):
BioCryst Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE March 23, 2020
First Posted Date  ICMJE April 1, 2020
Last Update Posted Date February 21, 2021
Actual Study Start Date  ICMJE March 3, 2020
Actual Primary Completion Date November 11, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 30, 2020)
  • Incidence of graded treatment-emergent adverse events [ Time Frame: Part 1: Day 16 ]
  • Incidence of graded treatment-emergent adverse events [ Time Frame: 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 [ Time Frame: Part 3:Day 44 or Week 50 (South Africa only) ]
  • Incidence of graded laboratory chemistry abnormalities [ Time Frame: Part 1: Day 16 ]
  • Incidence of graded laboratory chemistry abnormalities [ Time Frame: 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 [ Time Frame: Part 3:Day 44 or Week 50 (South Africa only) ]
  • Incidence of graded urinalysis abnormalities [ Time Frame: Part 1: Day 16 ]
  • Incidence of graded urinalysis abnormalities [ Time Frame: 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 [ Time Frame: Part 3: Day 44 or Week 50 (South Africa only) ]
  • Incidence of graded coagulation abnormalities [ Time Frame: Part 1: Day 16 ]
  • Incidence of graded coagulation abnormalities [ Time Frame: 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 [ Time Frame: Part 3: Day 44 or Week 50 (South Africa only) ]
  • Incidence of graded hematology abnormalities [ Time Frame: Part 1: Day 16 ]
  • Incidence of graded hematology abnormalities [ Time Frame: 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 [ Time Frame: Part 3: Day 44 or Week 50 (South Africa only) ]
  • Change from baseline in blood pressure [ Time Frame: Part 1: Day 16 ]
  • Change from baseline in blood pressure [ Time Frame: 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 [ Time Frame: Part 3: Day 44 or Week 50 (South Africa only) ]
  • Change from baseline in temperature [ Time Frame: Part 1: Day 16 ]
  • Change from baseline in temperature [ Time Frame: 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 [ Time Frame: Part 3: Day 44 or Week 50 (South Africa only) ]
  • Change from baseline in heart rate [ Time Frame: Part 1: Day 16 ]
  • Change from baseline in heart rate [ Time Frame: 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 [ Time Frame: Part 3: Day 44 or Week 50 (South Africa only) ]
  • Change from baseline in respiratory rate [ Time Frame: Part 3: Day 44 or Week 50 (South Africa only) ]
  • Change in Electrocardiogram (PR interval) [ Time Frame: Part 1: Day 16 ]
  • Change in Electrocardiogram (PR interval) [ Time Frame: 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) [ Time Frame: Part 3: Day 44 or Week 50 (South Africa only) ]
  • Change in Electrocardiogram (QRS interval) [ Time Frame: Part 1: Day 16 ]
  • Change in Electrocardiogram (QRS interval) [ Time Frame: 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) [ Time Frame: Part 3: Day 44 or Week 50 (South Africa only) ]
  • Change in Electrocardiogram (RR interval) [ Time Frame: Part 1: Day 16 ]
  • Change in Electrocardiogram (RR interval) [ Time Frame: 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) [ Time Frame: Part 3:Day 44 or Week 50 (South Africa only) ]
  • Change in Electrocardiogram (QT interval) [ Time Frame: Part 1: Day 16 ]
  • Change in Electrocardiogram (QT interval) [ Time Frame: 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) [ Time Frame: Part 3:Day 44 or Week 50 (South Africa only) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 30, 2020)
  • Plasma BCX9930 Cmax [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: plasma PK parameters are based on blood sampling through Day 4 for Part 1 ]
  • Plasma BCX9930 t1/2 [ Time Frame: 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 [ Time Frame: 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 ]
  • Serum AP complement activity [ Time Frame: Part 1:through Study Day 4; through Day 6, 14 or 18 for Part 2 (Day depends on dosing duration); and Part 3 through Day 28 or Week 48 (South Africa only) ]
  • Plasma Factor Bb [ Time Frame: Part 1:through Study Day 4; through Day 6, 14 or 18 for Part 2 (Day depends on dosing duration); and Part 3 through Day 28 or Week 48 (South Africa only) ]
  • Number of blood transfusions [ Time Frame: Part 3:baseline through Day 28 or Week 50 (South Africa only) ]
  • Lactate dehydrogenase [ Time Frame: Part 3: absolute and change from baseline through Day 28 or Week 50 (South Africa only) ]
  • Hemoglobin [ Time Frame: Part 3: absolute and change from baseline through Day 28 or Week 50 (South Africa only) ]
  • Absolute reticulocyte count [ Time Frame: Part 3: values and change from baseline through Day 28 or Week 50 (South Africa only) ]
  • Haptoglobin [ Time Frame: Part 3: absolute and change from baseline through Day 28 or Week 50 (South Africa only) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE First-in-Human Study of BCX9930 in Healthy Volunteers and Patients With PNH
Official Title  ICMJE A Phase 1 Dose-ranging Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of BCX9930 in Healthy Subjects and in Subjects With Paroxysmal Nocturnal Hemoglobinuria
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.
Detailed Description

Up to 6 sequential ascending dose cohorts are planned to be dosed in a sequential manner in Part 1 of the study. Eight subjects will be treated with a single dose of the study drug per dose cohort (6 subjects per cohort will receive BCX9930 and 2 subjects per cohort will receive matching placebo). Escalation to the next higher dose level will occur only after completion of a review of clinical safety and pharmacokinetics by the Sponsor and PI.

Up to 7 ascending, multiple dose cohorts will be enrolled in a sequential manner in Part 2 of the study. In Cohorts 1 through 3, twelve subjects will be treated with either a 7-day or 14-day course of study drug (10 subjects per cohort will receive BCX9930 and 2 subjects per cohort will receive matching placebo) administered orally. In Cohorts 4 through 7, twelve subjects will be treated with a 3-day course of study drug (10 subjects per cohort will receive BCX9930 and 2 subjects per cohort will receive matching placebo) administered orally. The daily dose may be split into 2 times daily (BID) or 3 times daily (TID) dosing for the multiple ascending dose part as needed. Escalation to the next higher dose level in Part 2 will occur only after completion of a review of clinical safety and pharmacokinetics by the Sponsor and PI.

Part 3 of the study consists of up to 2 sequential ascending multiple dose cohorts of up to 8 subjects; each cohort may enroll up to 4 subjects with PNH who are naïve to both eculizumab and ravulizumab and up to 4 subjects with PNH who are currently being treated with either eculizumab or ravulizumab. In each cohort, subjects will receive one daily dose of BCX9930 on Days 1 to 14 and a higher daily dose on Days 15 to 28. Cohort 2 will start after independent data monitoring committee (DMC) review of Cohort 1 data and communication of their evaluation to Part 3 investigators. In South Africa, subjects that have clinical benefit from BCX9930 will be allowed to continue dosing for up to 48 weeks.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
Each cohort in Part 3 is enrolled as a single group; Parts 1 and 2 follow a parallel study model.
Masking: None (Open Label)
Masking Description:
Part 3 is not masked; Parts 1 and 2 are participant and investigator masked.
Primary Purpose: Treatment
Condition  ICMJE Paroxysmal Nocturnal Hemoglobinuria
Intervention  ICMJE
  • Drug: BCX9930
    BCX9930 capsules for oral administration
  • Drug: Placebo
    placebo to match BCX9930 capsules for oral administration
Study Arms  ICMJE
  • Experimental: BCX9930
    Parts 1, 2 and 3
    Intervention: Drug: BCX9930
  • Placebo Comparator: Placebo
    Parts 1 and 2 only
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 18, 2021)
168
Original Estimated Enrollment  ICMJE
 (submitted: March 30, 2020)
148
Actual Study Completion Date  ICMJE January 25, 2021
Actual Primary Completion Date November 11, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria (Parts 1, 2, and 3):

  • 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

Key Inclusion Criteria (Parts 1 and 2):

  • 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

Key Inclusion Criteria (Part 3 only):

  • 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

Key Exclusion Criteria (Parts 1 and 2):

  • 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

Key Exclusion Criteria (Part 3):

  • 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
  • Current participation in any other investigational drug study or participation in an investigational drug study within 30 days of the screening visit
  • History of meningococcal disease
  • Positive drugs of abuse screen at screening visit
  • Pregnant, planning to become pregnant, or having been pregnant within 90 days of Day 1, or lactating
  • History of severe hypersensitivity to any drug
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE South Africa
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04330534
Other Study ID Numbers  ICMJE BCX9930-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party BioCryst Pharmaceuticals
Study Sponsor  ICMJE BioCryst Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Antionio Risitano University of Naples
PRS Account BioCryst Pharmaceuticals
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP