Study of Angiogenic Cell Therapy for Progressive Pulmonary Hypertension

NCT03001414 | Terminated Phase 2 Results DMC

• 1 other identifier: CT-PAH002
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 4

Brief Summary

The SAPPHIRE clinical trial seeks to establish the efficacy and safety of repeated monthly dosing of autologous EPCs transfected with human eNOS (heNOS) in patients with symptomatic severe PAH on available PAH-targeted medical therapy.

Conditions

Hypertension,Pulmonary

Outcome Measures

Primary Outcomes (1)

• Change in 6 Minute Walk Distance (6MWD) From Baseline

  Change was calculated as the distance walked at 6 months minus the distance at baseline.

  Baseline, 6 months

Secondary Outcomes (8)

• Change in 6 Minute Walk Distance (6MWD) From Baseline

  Baseline and 12 months

• Change in 6 Minute Walk Distance (6MWD) From Baseline

  Baseline, 6 months, 12 months

• Change in 6MWD From Baseline

  Baseline, 6 months, 12 months

• Change in Pulmonary Vascular Resistance From Baseline

  6 months

• Change in Pulmonary Vascular Resistance From Baseline

  Baseline and 12 months

Study Arms (3)

Placebo followed by Autologous EPCs transfected with eNOS

EXPERIMENTAL

4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 1 followed by 4 monthly IV injections of Autologous EPCs transfected with human eNOS (total of 80 million cells) during Course 2

Biological: Placebo followed by Autologous EPCs transfected with human eNOS

Autologous EPCs transfected with eNOS followed by Placebo

EXPERIMENTAL

4 monthly IV injections of Autologous EPCs transfected with human eNOS (total of 80 million cells) during Course 1 followed by 4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 2

Biological: Autologous EPCs transfected with human eNOS followed by Placebo

Autologous EPCs transfected with eNOS

EXPERIMENTAL

4 monthly IV injections of Autologous EPCs transfected with human eNOS in Course 1 followed by 4 monthly injections of Autologous EPCs transfected with human eNOS in Course 2 (total of 160 million cells)

Biological: Autologous EPCs transfected with human eNOS

Interventions

Placebo followed by Autologous EPCs transfected with human eNOS BIOLOGICAL

4 doses of placebo in first 6 months followed by 4 doses of autologous EPCs transfected with eNOS in second 6 months

Placebo followed by Autologous EPCs transfected with eNOS

Autologous EPCs transfected with human eNOS followed by Placebo BIOLOGICAL

4 doses of autologous EPCs transfected with eNOS in first 6 months followed by 4 doses of placebo in second 6 months

Autologous EPCs transfected with eNOS followed by Placebo

Autologous EPCs transfected with human eNOS BIOLOGICAL

4 doses of autologous EPCs transfected with eNOS in first 6 months which is repeated in second 6 months

Autologous EPCs transfected with eNOS

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years, ≤ 80 years
• Established diagnosis of PAH due to the following:
• Idiopathic or heritable PAH;
• Scleroderma associated PAH (limited or diffuse);
• Drugs (anorexigens) or toxins;
• Congenital heart defects (atrial septal defects, ventricular septal defects, and patent ductus arteriosus) repaired ≥ 1 years
• World Health Organization (WHO) functional class II, III, or IV on appropriate stable therapy for PAH for at least 3 months prior to the screening period and up until randomization, apart from modification of anticoagulant or diuretic dosages, or small adjustments in prostaglandin dose that are considered by the Investigator to be consistent with stable parenteral therapy.
• Able to walk unassisted (oxygen use allowed). Aids for carrying oxygen (such as a wheel chair or walker) are permitted provided they are not also required as mobility aids.
• An average 6-Minute Walk Distance (6MWD) of ≥ 125 meters and ≤ 440 meters on two consecutive tests during the Screening period
• Previous diagnostic right heart cardiac catheterization (RHC) at the time of PAH diagnosis with findings consistent with PAH: specifically, mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg (at rest); pulmonary vascular resistance (PVR) ≥ 3 WU; pulmonary capillary wedge pressure (PCWP) (or left ventricular end diastolic pressure) ≤12 mmHg if PVR ≥ 3 to \< 5 Woods Units (WU), or pulmonary capillary wedge pressure (PCWP) (or left ventricular end diastolic pressure) ≤ 15 mmHg if PVR ≥ 5 WU. If repeat testing has occurred since initial diagnosis, the most recent results should be used.
• Echocardiography performed within 12 months prior to the Screening Period confirming a left atrial volume index (LAVI) of ≤ 34 ml/m2 and the absence of any clinically significant left heart disease including evidence of more than mild left-sided valvular heart disease, systolic or diastolic left ventricular dysfunction
• Ventilation and perfusion (VQ) nuclear scan performed as part of the initial workup to establish the diagnosis of PAH showing absence (i.e. low probability) of pulmonary embolism. If repeat testing has occurred since initial diagnosis, the most recent results should be used. In the absence of a VQ scan to establish eligibility, a CT angiogram that has been reviewed by a radiologist with expertise in the work up for pulmonary endarterectomy and deemed negative for chronic thromboembolic disease may be used instead.
• Pulmonary function tests conducted within 2 years prior to the Screening Period to confirm: total lung capacity (TLC) ≥ 65% the predicted value; and forced expiratory volume at one second (FEV1) of ≥ 65% the predicted value
• Must have a resting arterial oxygen saturation (SaO2) ≥88% with or without supplemental oxygen as measured by pulse oximetry at the Screening Visit
• Must not be enrolled in an exercise training program for pulmonary rehabilitation within 3 months prior to the Screening Visit and must agree not to enroll in an exercise training program for pulmonary rehabilitation during the Screening Period and the first 6 months of the study. Participants enrolled in an exercise program for pulmonary rehabilitation 3 months prior to screening may enter the study if they agree to maintain their current level of rehabilitation for the first 6 months of the study

You may not qualify if:

• Pregnant or lactating
• Evidence of more than mild interstitial lung disease on Chest CT within the last 5 years (last 3 years for patients with scleroderma associated PAH)
• Treatment with an investigational drug, device or therapy within 3 months prior to the screening period or is scheduled to receive an investigational drug, device or therapy during the course of the study
• Any musculoskeletal disease or any other disease that would significantly limit ambulation
• Unrepaired or recently repaired (\< 1 year) congenital systemic-to-pulmonary shunt other than patent foramen ovale
• Patients having three or more of the following four AMBITION study heart failure preserved ejection fractio (HFpEF) risk factors will be excluded:
• BMI ≥ 30 kg/m2,
• History of essential hypertension,
• Diabetes mellitus (any type)
• Historical evidence of significant coronary artery disease (CAD) by any one of the following:
• History of myocardial infarction (MI)
• History of percutaneous coronary intervention (PCI)
• Prior coronary angiography evidence of CAD (\>50% stenosis in ≥1 vessel)
• Previous positive Stress Test
• Previousoronary artery bypass grafting (CABG)

Sponsors & Collaborators

• Northern Therapeutics: lead
• Ottawa Hospital Research Institute: collaborator

Study Sites (4)

Peter Lougheed Center, University of Calgary

Calgary, Alberta, T1Y 6J4, Canada

Location

London Health Sciences Center

London, Ontario, N6A 5W9, Canada

Location

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

Location

MeSH Terms

Conditions

Hypertension, Pulmonary

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Limitations and Caveats

Due to the corona virus disease (COVID)-19 pandemic, the trial was stopped after only 12 of the planned 45 patients were enrolled and randomized. This resulted in insufficient power for a reliable statistical analysis and necessitated a change to the analysis methods.

Results Point of Contact

• Title: Duncan Stewart, Clinical Trial Medical Consultant
• Organization: Northern Therapeutics, Inc.

djstewart@toh.ca

613-737-8899

Study Officials

• Duncan J Stewart, MD FRCPC

  Northern Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2016
• First Posted: December 23, 2016
• Study Start: September 28, 2017
• Primary Completion: May 4, 2023
• Study Completion: November 1, 2023
• Last Updated: January 31, 2025
• Results First Posted: January 31, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)