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

NCT03315507 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: PB1046-PT-CL-0005
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

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.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (12)

• Adverse Events

  Incidence and severity of AEs (described descriptively) and their relationship to study drug

  Pre-dose to 28 days after last dose

• Vital Signs (Blood pressure)

  Changes from baseline in blood pressure and their relationship to study drug

  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.

• Vital Signs (Heart rate)

  Changes from baseline in heart rate and their relationship to study drug

  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.

• Laboratory Parameters (Lipids)

  Changes from baseline in lipids and their relationship to study drug

  Pre-dose and 7 and 28 days after last dose

• Laboratory Parameters (Serum chemistry)

  Changes from baseline in serum chemistry and their relationship to study drug

  Pre-dose and prior to doses 2-8 and 7 and 28 days after last dose

• Laboratory Parameters (Urinalysis)

  Changes from baseline in urinalysis and their relationship to study drug

  Pre-dose and prior to doses 2-8 and 7 and 28 days after last dose

• Laboratory Parameters (NT-pro-BNP)

  Changes from baseline in NT-pro-BNP and their relationship to study drug

  Prior to doses 1-8 and 7 and 28 days after last dose

• Mean Pulmonary Artery Pressure

  Change from baseline in mean pulmonary artery pressure

  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

• Cardiac Index

  Change from baseline in cardiac index

  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

• Total pulmonary resistance

  Change from baseline in total pulmonary resistance

  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

• Laboratory Parameters (Fasting Plasma Glucose)

  Changes from baseline in fasting plasma glucose and their relationship to study drug

  Pre-dose and 7 and 28 days after last dose

• Laboratory Parameters (Hematology)

  Changes from baseline in hematology and their relationship to study drug

  Pre-dose and prior to doses 2-8 and 7 and 28 days after last dose

Secondary Outcomes (10)

• Pharmacokinetic Dose Exposures (AUC (0-t))

  Prior to eight weekly doses and at 1, 3, 24, 48, 72,120, 168 and 192 hours after final dose.

• Pharmacokinetic Dose Exposures (AUC (0-tmax))

  Prior to eight weekly doses and at 1, 3, 24, 48, 72,120, 168 and 192 hours after final dose.

• Pharmacokinetic Dose Exposures (Cmax)

  Prior to eight weekly doses and at 1, 3, 24, 48, 72,120, 168 and 192 hours after final dose.

• Pharmacokinetic Dose Exposures (Tmax)

  Prior to eight weekly doses and at 1, 3, 24, 48, 72,120, 168 and 192 hours after final dose.

• Pharmacokinetic Dose Exposures (Ctrough)

  Prior to eight weekly doses and at 1, 3, 24, 48, 72,120, 168 and 192 hours after final dose.

Other Outcomes (3)

• 6 Minute Walk Distance Test (6MWD)

  Pre-dose and 7 days after final dose

• Borg Dyspnea Index (BDI)

  Pre-dose and 7 days after final dose

• PAH Related Biomarkers

  Prior to Dose 1, prior to Dose 5 and 7 days after final dose

Study Arms (1)

PB1046 Injection

EXPERIMENTAL

PB1046 Subcutaneous Injection

Drug: PB1046 Subcutaneous Injection

Interventions

PB1046 Subcutaneous Injection DRUG

Eight weekly doses of PB1046.

PB1046 Injection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• PhaseBio Pharmaceuticals Inc.: lead

Study Sites (2)

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open Label

Study Record Dates

• First Submitted: October 2, 2017
• First Posted: October 20, 2017
• Study Start: October 20, 2017
• Primary Completion: August 8, 2019
• Study Completion: August 8, 2019
• Last Updated: October 8, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)