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

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

Tracking Information

• First Submitted Date: October 2, 2017
• First Posted Date: October 20, 2017
• Last Update Posted Date: October 8, 2019
• Actual Study Start Date: October 20, 2017
• Actual Primary Completion Date: August 8, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: 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: A Study to Assess the Safety, Tolerability, and Hemodynamic Response of PB1046 in Subjects With PAH
• Official Title: 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: Interventional
• Study Phase: Phase 1

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Open Label

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Pulmonary Arterial Hypertension

Intervention

Drug: PB1046 Subcutaneous Injection

Eight weekly doses of PB1046.

Study Arms

Experimental: PB1046 Injection

PB1046 Subcutaneous Injection

Intervention: Drug: PB1046 Subcutaneous Injection

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 7, 2019): 3
• Original Estimated Enrollment (submitted: October 16, 2017): 10
• Actual Study Completion Date: August 8, 2019
• Actual Primary Completion Date: August 8, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03315507
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Current Responsible Party: PhaseBio Pharmaceuticals Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: PhaseBio Pharmaceuticals Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: PhaseBio Pharmaceuticals Inc.
• Verification Date: October 2019