Angiogenic Cell Therapy for Pulmonary Hypertension

(SAPPHIRE Trial)

No longer recruiting at 6 trial locations

Overseen By Kim Danovitch, CCRP

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Northern Therapeutics

Must be taking: PAH-targeted therapy

Must not be taking: Investigational drugs

Disqualifiers: Pregnancy, Hypertension, Diabetes, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 21

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with severe pulmonary arterial hypertension (PAH), a condition that causes high blood pressure in the lungs and makes breathing difficult. The study explores whether repeated monthly doses of special cells (autologous EPCs transfected with human eNOS, taken from the patient and treated to enhance blood flow) can improve symptoms. Participants will receive these cells or a placebo in different sequences to assess the treatment's effectiveness. Individuals with PAH due to conditions like scleroderma or repaired heart defects, who struggle with daily activities because of their symptoms, might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial does not specify that you need to stop your current medications. In fact, it requires participants to be on stable PAH-targeted therapy for at least 3 months before joining. However, you should discuss your specific medications with the trial team to ensure they are compatible with the study requirements.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using a person's own stem cells, modified with a gene that helps blood vessels relax, appears safe. Clinical studies have examined patient responses to these treatments and suggest that they are generally well-tolerated, with no major safety concerns reported.

Some patients have experienced mild side effects, but these are usually manageable. Since this treatment is being tested in advanced stages of clinical trials, evidence already indicates its safety for human use. Additionally, studies in animals, such as rats and dogs, have shown that these cells can help reduce symptoms of high blood pressure in the lungs without causing harm.

Overall, the available data suggest that this treatment is likely safe, but ongoing research remains crucial to confirm these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike standard treatments for pulmonary hypertension, which often include medications like endothelin receptor antagonists or phosphodiesterase-5 inhibitors, this investigational therapy uses autologous endothelial progenitor cells (EPCs) transfected with human endothelial nitric oxide synthase (eNOS). This approach is unique because it focuses on enhancing the body's own ability to repair and improve blood vessel function by boosting nitric oxide production, which is crucial for vasodilation and improved blood flow. Researchers are excited about this treatment because it targets the root cause of the disease rather than just managing symptoms, potentially offering a more effective and long-lasting solution for patients.

What evidence suggests that this trial's treatments could be effective for pulmonary hypertension?

Research has shown that using a person's own endothelial progenitor cells (EPCs), modified with a gene to help blood vessels relax, may treat pulmonary arterial hypertension (PAH). In this trial, participants will receive different treatments involving these modified EPCs. Studies have found that these cells can improve blood flow in the lungs, potentially easing symptoms for people with severe PAH. Early results indicated that patients receiving these cells walked longer distances. This improvement stems from the cells' ability to enhance blood vessel function in the lungs, suggesting that the treatment could effectively manage PAH symptoms. ^{1 2 3 6 7}

Who Is on the Research Team?

Duncan J Stewart, MD FRCPC

Principal Investigator

Northern Therapeutics, Inc.

Are You a Good Fit for This Trial?

Adults aged 18-80 with severe Pulmonary Arterial Hypertension (PAH) due to conditions like scleroderma or congenital heart defects, not participating in other trials or pulmonary rehab recently. Must be on stable PAH therapy for at least 3 months, able to walk unassisted, and meet specific criteria on diagnostic tests.

Inclusion Criteria

My PAH is classified as moderate to severe, and I've been on stable treatment for over 3 months.

I had surgery to fix a heart defect more than a year ago.

I can walk between 125 and 440 meters in 6 minutes.

Exclusion Criteria

I do not have a disease that severely limits my ability to walk.

You have three or more specific risk factors for heart failure with preserved ejection fraction (HFpEF) mentioned in the AMBITION study.

You have participated in gene therapy or studies involving certain protein growth factors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Apheresis and Randomization

Participants undergo apheresis for cell collection and are randomized to treatment arms

1 week

1 visit (in-person)

Treatment Course 1

Participants receive 4 monthly IV infusions according to their assigned treatment arm

6 months

4 visits (in-person)

Treatment Course 2

Participants receive another 4 monthly IV infusions according to their assigned treatment arm

6 months

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

11 visits (in-person)

Long-term Registry

Participants are followed for long-term safety information through annual telephone contacts

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Autologous EPCs transfected with human eNOS

Trial Overview The SAPPHIRE trial is testing the safety and effectiveness of monthly doses of autologous EPCs enhanced with human eNOS gene against a placebo in improving symptoms of PAH. Participants will receive either the treatment first followed by placebo or vice versa.

How Is the Trial Designed?

Group I: Placebo followed by Autologous EPCs transfected with eNOS Experimental Treatment 1 Intervention

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

Group II: Autologous EPCs transfected with eNOS followed by Placebo Experimental Treatment 1 Intervention

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

Group III: Autologous EPCs transfected with eNOS Experimental Treatment 1 Intervention

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)

Who Is Running the Clinical Trial?

Northern Therapeutics

Lead Sponsor

Trials

3

Recruited

40+

Ottawa Hospital Research Institute

Collaborator

Trials

585

Recruited

3,283,000+

Citations

1. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/14/NCT03001414/Prot_000.pdf

Intervention with Repeat dosing of eNOS-enhanced EPCs A late phase clinical trial to establish the efficacy and safety of repeat dosing of autologous endothelial progenitor cells (EPCs) transfected ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6351342/

Clinical trial design and new therapies for pulmonary arterial ... Autologous EPCs transfected with human eNOS, NCT03001414, Multicentre double ... Predicting outcomes in pulmonary arterial hypertension based on the 6-minute walk ...

3. ahajournals.org ahajournals.org/doi/10.1161/circresaha.114.305951

Endothelial NO-Synthase Gene-Enhanced Progenitor Cell ... We now report that administration of eNOS-transfected early outgrowth EPCs into the pulmonary circulation of patients with stable severe PAH ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00469027

Study Details | NCT00469027 | Pulmonary Hypertension: ... The primary objective is to establish the safety of autologous progenitor cell-based gene therapy of heNOS in patients with severe Pulmonary Arterial ...

5. nature.com nature.com/articles/hr2012217

Therapeutic effect of eNOS-transfected endothelial ... These findings indicate a critical role of eNOS in HPAH treatment and suggest that eNOS-transfected EPCs may provide an effective strategy for HPAH treatment ...

6. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT03001414/

Trial | NCT03001414 The SAPPHIRE clinical trial seeks to establish the efficacy and safety of repeated monthly dosing of autologous EPCs transfected with human eNOS (heNOS) in ...

7. jacc.org jacc.org/doi/10.1016/j.jacc.2006.12.037

Transplantation of Autologous Endothelial Progenitor Cells ... Experimental data suggest that transplantation of EPCs attenuates monocrotaline-induced pulmonary hypertension in rats and dogs. In addition, clinical studies ...