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A Study to Assess the Safety, Tolerability, and Hemodynamic Response of PB1046 in Subjects With PAH

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: NCT03315507
Recruitment Status : Completed
First Posted : October 20, 2017
Last Update Posted : October 8, 2019
Sponsor:
Information provided by (Responsible Party):
PhaseBio Pharmaceuticals Inc.

Tracking Information
First Submitted Date  ICMJE October 2, 2017
First Posted Date  ICMJE October 20, 2017
Last Update Posted Date October 8, 2019
Actual Study Start Date  ICMJE October 20, 2017
Actual Primary Completion Date August 8, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 16, 2017)
  • Adverse Events [ Time Frame: Pre-dose to 28 days after last dose ]
    Incidence and severity of AEs (described descriptively) and their relationship to study drug
  • Vital Signs (Blood pressure) [ Time Frame: Prior to eight weekly doses and 1 and 3 hours after the final dose and 1, 2, 3, 5, 7 and 28 days after final dose. ]
    Changes from baseline in blood pressure and their relationship to study drug
  • Vital Signs (Heart rate) [ Time Frame: Prior to eight weekly doses and 1 and 3 hours after the final dose and 1, 2, 3, 5, 7 and 28 days after final dose. ]
    Changes from baseline in heart rate and their relationship to study drug
  • Laboratory Parameters (Lipids) [ Time Frame: Pre-dose and 7 and 28 days after last dose ]
    Changes from baseline in lipids and their relationship to study drug
  • Laboratory Parameters (Serum chemistry) [ Time Frame: Pre-dose and prior to doses 2-8 and 7 and 28 days after last dose ]
    Changes from baseline in serum chemistry and their relationship to study drug
  • Laboratory Parameters (Urinalysis) [ Time Frame: Pre-dose and prior to doses 2-8 and 7 and 28 days after last dose ]
    Changes from baseline in urinalysis and their relationship to study drug
  • Laboratory Parameters (NT-pro-BNP) [ Time Frame: Prior to doses 1-8 and 7 and 28 days after last dose ]
    Changes from baseline in NT-pro-BNP and their relationship to study drug
  • Mean Pulmonary Artery Pressure [ Time Frame: Prior to eight weekly doses and 1 and 3 hours after the final dose and 1, 2, 3, 5, 7, 8 and 28 days after final dose ]
    Change from baseline in mean pulmonary artery pressure
  • Cardiac Index [ Time Frame: Prior to eight weekly doses and 1 and 3 hours after the final dose and 1, 2, 3, 5, 7, 8 and 28 days after final dose ]
    Change from baseline in cardiac index
  • Total pulmonary resistance [ Time Frame: Prior to eight weekly doses and 1 and 3 hours after the final dose and 1, 2, 3, 5, 7, 8 and 28 days after final dose ]
    Change from baseline in total pulmonary resistance
  • Laboratory Parameters (Fasting Plasma Glucose) [ Time Frame: Pre-dose and 7 and 28 days after last dose ]
    Changes from baseline in fasting plasma glucose and their relationship to study drug
  • Laboratory Parameters (Hematology) [ Time Frame: Pre-dose and prior to doses 2-8 and 7 and 28 days after last dose ]
    Changes from baseline in hematology and their relationship to study drug
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03315507 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2017)
  • Pharmacokinetic Dose Exposures (AUC (0-t)) [ Time Frame: Prior to eight weekly doses and at 1, 3, 24, 48, 72,120, 168 and 192 hours after final dose. ]
    Area under the curve over the dosing interval (AUC(0-t))
  • Pharmacokinetic Dose Exposures (AUC (0-tmax)) [ Time Frame: Prior to eight weekly doses and at 1, 3, 24, 48, 72,120, 168 and 192 hours after final dose. ]
    Area under the curve concentration-time profile (AUC(0-tmax))
  • Pharmacokinetic Dose Exposures (Cmax) [ Time Frame: Prior to eight weekly doses and at 1, 3, 24, 48, 72,120, 168 and 192 hours after final dose. ]
    Maximum serum concentration (Cmax)
  • Pharmacokinetic Dose Exposures (Tmax) [ Time Frame: Prior to eight weekly doses and at 1, 3, 24, 48, 72,120, 168 and 192 hours after final dose. ]
    Time to Cmax (Tmax)
  • Pharmacokinetic Dose Exposures (Ctrough) [ Time Frame: Prior to eight weekly doses and at 1, 3, 24, 48, 72,120, 168 and 192 hours after final dose. ]
    Pre-dose serum concentrations at Weeks 1 through 7 and the concentrations after the last dose
  • Pharmacokinetic Dose Exposures (t1/2) [ Time Frame: Prior to eight weekly doses and at 1, 3, 24, 48, 72,120, 168 and 192 hours after final dose. ]
    Half-life (t1/2)
  • Pharmacokinetic Dose Exposures (Lambda z) [ Time Frame: Prior to eight weekly doses and at 1, 3, 24, 48, 72,120, 168 and 192 hours after final dose. ]
    Lambda z
  • Pharmacokinetic Dose Exposures (Cl/F) [ Time Frame: Prior to eight weekly doses and at 1, 3, 24, 48, 72,120, 168 and 192 hours after final dose. ]
    Apparent clearance (Cl/F)
  • Pharmacokinetic Dose Exposures (Vd/F) [ Time Frame: Prior to eight weekly doses and at 1, 3, 24, 48, 72,120, 168 and 192 hours after final dose. ]
    Volume of distribution (Vd/F)
  • Immunogenicity [ Time Frame: Prior to eight weekly doses and on study days 59, 77 and 105. ]
    Incidence of immunogenicity
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 16, 2017)
  • 6 Minute Walk Distance Test (6MWD) [ Time Frame: Pre-dose and 7 days after final dose ]
    Change from baseline in 6MWD
  • Borg Dyspnea Index (BDI) [ Time Frame: Pre-dose and 7 days after final dose ]
    Change from baseline in BDI
  • PAH Related Biomarkers [ Time Frame: Prior to Dose 1, prior to Dose 5 and 7 days after final dose ]
    Change from baseline in PAH related biomarkers
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE A Study to Assess the Safety, Tolerability, and Hemodynamic Response of PB1046 in Subjects With PAH
Official Title  ICMJE An Open-Label, Dose Titration Study to Assess the Safety, Tolerability, and Hemodynamic Response of PB1046, A Sustained-Release Analogue of Vasoactive Intestinal Peptide, In Adult Subjects With Pulmonary Arterial Hypertension
Brief Summary PB1046-PT-CL-0005 is an open-label, dose-titration study to assess the safety, tolerability, and hemodynamic effects of individually dose-titrated PB1046 administered by weekly subcutaneous injection for 8 weeks in adult subjects with PAH who have a permanently implanted hemodynamic monitor in the distal pulmonary artery. The primary objectives of the study are to assess the overall safety, tolerability, and hemodynamic profile of a PB1046 across an individually titrated dose range.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
Open Label
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pulmonary Arterial Hypertension
Intervention  ICMJE Drug: PB1046 Subcutaneous Injection
Eight weekly doses of PB1046.
Study Arms  ICMJE Experimental: PB1046 Injection
PB1046 Subcutaneous Injection
Intervention: Drug: PB1046 Subcutaneous Injection
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: October 7, 2019)
3
Original Estimated Enrollment  ICMJE
 (submitted: October 16, 2017)
10
Actual Study Completion Date  ICMJE August 8, 2019
Actual Primary Completion Date August 8, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Willing and able to provide written informed consent and follow all study-related procedures;
  • Confirmed diagnosis of Pulmonary Arterial Hypertension (WHO Group 1) and WHO Functional Class II or III by clinical diagnostic criteria assessed by the Investigator and have a permanently implanted pulmonary artery hemodynamic monitor (IHM);
  • Adult subjects ≥18 years of age willing and able to utilize contraception as needed for 30 days after their last dose of study drug;
  • Body mass index ≥ 18 kg/m2 and ≤ 47 kg/m2;
  • Receipt of Investigator-directed stable (no change in dose or addition or removal of a therapy) medical-therapy in accordance with local standard of care for the management of PAH for 30 days prior to screening and between screening and first dose and are in stable clinical condition;
  • Screening hemoglobin ≥ 9.0 g/dL secondary to the volume of blood to be collected during the study period;
  • Willing and able to return to the study unit for specified study visits, or accommodate home visits;
  • Willing and able to transmit hemodynamics via IHM and monitor systemic blood pressure while at home and record results.

Exclusion Criteria:

  • Concomitant medical disorder, condition, or history, that in the opinion of the Investigator would impair the subject's ability to participate in or complete the requirements of the study;
  • Concomitant medical disorder that is expected to limit the subject's life-expectancy to ≤ 1 year;
  • Pregnant or lactating female subjects;
  • First positive result from serology testing at visit 1 (screening labs) for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus prior to first dose;
  • Participation in another investigational study within 30 days prior to screening or are taking part in a non-medication study which, in the opinion of the Investigator, would interfere with the study compliance or outcome assessments;
  • Use of bosentan therapy for PAH within 30 days prior to screening or during study participation;
  • Sustained systolic blood pressure (SBP) < 95 mmHg and/or diastolic blood pressure (DBP) < 50 mmHg (confirmed by a duplicate seated reading) on at least 3 consecutive readings (self-monitored or office) prior to first dose, or overt symptomatic hypotension;
  • Sustained resting heart rate >110 beats per minute (BPM) at screening (V1) or prior to first dose (confirmed by duplicate assessments of office vital signs or consecutive ECG assessments) on at least 3 consecutive readings prior to first dose;
  • Clinically significant renal dysfunction as measured by the estimated glomerular filtration rate (eGFR) of < 40 mL/min/1.73m2 as calculated by the MDRD equation: eGFR = 175 x (Creat / 88.4)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if African American) (conventional units);
  • Clinically significant liver dysfunction as measured by any one of the following: a. alanine aminotransferase (ALT) >3.0 time ULN or; b. aspartate aminotransferase (AST) >3.0 time ULN or; c. serum bilirubin ≥ 1.6 mg/dL;
  • Known history of substance abuse that in the opinion of the Investigator would impair the subject's ability to participate in or complete the requirements of the study;
  • Any major surgical procedure within 30 days prior to screening or planned surgical procedure during the study period;
  • In-patient hospitalization (defined as greater than 23 hours) within 30 days of subject dosing;
  • Enrollment within the past 3 months prior to screening or plans to enroll during the study into a cardiopulmonary rehabilitation program;
  • Other medical or psychiatric condition which, in the opinion of the Investigator, would place the subject at increased risk or would preclude obtaining voluntary consent or would confound the objectives of study;
  • Known hypersensitivity to study drug or any of the excipients of the drug formulation.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03315507
Other Study ID Numbers  ICMJE PB1046-PT-CL-0005
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party PhaseBio Pharmaceuticals Inc.
Study Sponsor  ICMJE PhaseBio Pharmaceuticals Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account PhaseBio Pharmaceuticals Inc.
Verification Date October 2019

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