NCT03363165: HI-PAD

Hepatocyte Growth Factor to Improve Functioning in PAD

Completed Phase 2 Results posted Last updated 30 May 2024

What this trial tests

Phase 2 trial testing VM202 in Peripheral Artery Disease in 39 participants. Completed in 5 September 2023.

Timeline

1 January 2018

Primary endpoint
10 February 2023

5 September 2023

Quick facts

Lead sponsor	Northwestern University
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	39
Start date	1 January 2018
Primary completion	10 February 2023
Estimated completion	5 September 2023
Sites	1 location across United States

Drugs / interventions tested

• VM202 — full drug profile →
• Placebo

Conditions studied

• Peripheral Artery Disease — all drugs for Peripheral Artery Disease →

Sponsor

Northwestern University

Who can join

55 and older, any sex, with Peripheral Artery Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Six-minute Walk Distance Primary · Change from baseline to six-month follow-up in six-minute walk distance

Participants walking up and down a 100 foot hallway for six minutes following a standardized protocol. The goal is for them to walk as far as possible in six minutes

Group	Value	95% CI
Placebo	17.01	± 13.76
VM202	3.46	± 12.70

Maximal Treadmill Walking Time Secondary · Change from baseline to three-month follow-up

A Gardner or Modified Gardner treadmill exercise protocol will be used

Group	Value	95% CI
Placebo	-0.59	± 0.73
VM202	1.66	± 0.73

Calf Muscle Perfusion Secondary · Change from baseline to three-month follow-up

Calf muscle perfusion is measured by Magnetic Resonance Imaging (MRI) Unit of measure is ml/minute per 100 gms tissue

Group	Value	95% CI
Placebo	1.98	± 1.90
VM202	2.68	± 1.87

Calf Muscle Biopsy Biochemical Measures (Satellite Cells - Total SCs/100 Fibers) Secondary · Change from baseline to three-month follow-up

A skeletal muscle sample will be obtained from the calf muscle. The outcome is the number of satellite cells per 100 muscle fibers

Group	Value	95% CI
Placebo	-4.83	± 8.23
VM202	3.45	± 6.91

Walking Impairment Questionnaire - Distance Score Secondary · Change from baseline to three-month follow-up

The well validated Walking Impairment Questionnaire will be used to measure patient- perceived walking performance. The WIQ is scored from 0-100, with 100 being the best score. We will use distance and speed sub-components separately.

Group	Value	95% CI
Placebo	6.28	± 5.54
VM202	8.30	± 5.19

The Short-Form-36 Physical Functioning Score Secondary · Change from baseline to three-month follow-up

This well validated quality of life measure will be used to assess changes in patient perceived quality of life. The SF-36 is scored from 0-100, with 100 being the best score.

Group	Value	95% CI
Placebo	8.70	± 4.94
VM202	3.20	± 4.60

The Short-Form-36 Physical Functioning Score Secondary · Change from baseline to six-month follow-up

This well validated quality of life measure will be used to assess changes in patient perceived quality of life. Scored on a 0-100 scale, where 100- is best.

Group	Value	95% CI
Placebo	11.98	± 3.67
VM202	6.84	± 3.32

Walking Impairment Questionnaire - Distance Score Secondary · Change from baseline to six-month follow-up

The well validated Walking Impairment Questionnaire will be used to measure patient- perceived walking performance.

Group	Value	95% CI
Placebo	11.44	± 6.63
VM202	9.31	± 6.01

Six-minute Walk Distance Secondary · Change in six-minute walk distance from baseline to three-month follow-up

Participants walking up and down a 100 foot hallway for six minutes following a standardized protocol. The goal is for them to walk as far as possible in six minutes

Group	Value	95% CI
Placebo	-0.48	± 12.80
VM202	-2.49	± 12.01

Pain-free Treadmill Walking Time Secondary · Change from baseline to three-month follow-up

A Gardner or Modified Gardner treadmill exercise protocol will be used

Group	Value	95% CI
Placebo	0.95	± 0.80
VM202	0.45	± 0.77

Six-minute Walk Distance Secondary · Change from baseline to 12-month follow-up in six minute walk distance.

See above regarding 6-minute walk protocol

Group	Value	95% CI
Placebo	5.02	± 12.17
VM202	2.24	± 11.17

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events forms are collected at 2nd, 3rd, and 4th injection days, as well as the 3-month, 6-month, and 12-month follow-up visits.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 6/18 (33%)

Deaths: 1/18

VM202

Serious: 6/21 (29%)

Deaths: 1/21

Serious adverse events (14 terms)

Reaction	System	Placebo	VM202
Pneumonia	Respiratory, thoracic and mediastinal disorders	—	—
Lower extremity revascularization	General disorders	—	—
Chest pain	General disorders	—	—
Fall and fracture	General disorders	—	—
Dehydration	General disorders	—	—
Bowel obstruction	General disorders	—	—
Colonoscopy	General disorders	—	—
Palpitations and anemia	General disorders	—	—
Blood transfusion/anemia	General disorders	—	—
COVID-19	Respiratory, thoracic and mediastinal disorders	—	—
Pulled muscle	General disorders	—	—
Hypertension	General disorders	—	—
COPD exacerbation	General disorders	—	—
Lower extremity arterial bypass surgery	General disorders	—	—

Other adverse events (7 terms — click to expand)

Reaction	System	Placebo	VM202
Pain or discomfort at the study drug injection sites	General disorders	—	—
Stayed overnight in the hospital	General disorders	—	—
Redness or irritation at the study drug injection sites	General disorders	—	—
Venous thromboembolism (deep venous thrombosis or pulmonary embolism)	General disorders	—	—
Diagnosed with infection at any of the injection sites	General disorders	—	—
Eye disease - proliferative retinopathy	General disorders	—	—
Diagnosed with a new tumor or cancer	General disorders	—	—

Most-reported serious reactions: Pneumonia, Lower extremity revascularization, Chest pain, Fall and fracture, Dehydration, Bowel obstruction, Colonoscopy, Palpitations and anemia.

Data from ClinicalTrials.gov NCT03363165 adverse events section.

Sponsor's own description

HI-PAD is a placebo controlled double-blind randomized pilot clinical trial to determine whether VM202 may improve walking ability in people with lower extremity peripheral artery disease (PAD).

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Therapeutic angiogenesis-based strategy for peripheral artery disease.
   Han J, Luo L, Marcelina O, Kasim V, et al · · 2022 · cited 46× · PMID 35836800 · DOI 10.7150/thno.74785
2. Recent highlights and advances in cardiac gene therapy.
   Oh JG, Ishikawa K. · · 2019 · cited 4× · PMID 32053763
3. Translational Relevance of Advanced Age and Atherosclerosis in Preclinical Trials of Biotherapies for Peripheral Artery Disease.
   Webster KA. · · 2024 · cited 3× · PMID 38275616 · DOI 10.3390/genes15010135
4. Hepatocyte growth factor for walking performance in peripheral artery disease.
   McDermott MM, Sufit R, Domanchuk KJ, Volpe NJ, et al · · 2025 · cited 2× · PMID 39778757 · DOI 10.1016/j.jvs.2024.12.124
5. Medical therapies, comorbid conditions, and functional performance in people with peripheral artery disease enrolled in clinical trials between 2004 and 2021.
   Nayak P, Polonsky T, Tian L, Greenland P, et al · · 2023 · cited 1× · PMID 36588397 · DOI 10.1177/1358863x221145533
6. Community-based recruitment with ankle brachial index testing to identify peripheral artery disease participants for randomized clinical trials.
   McDermott MM, Cetlin MD, Domanchuk KJ, Xu S, et al · · 2026 · PMID 42035974 · DOI 10.1016/j.ahj.2026.107450
7. Gastrocnemius Myofiber Type and Mitochondrial Alterations Associated With Peripheral Artery Disease Severity.
   Kosmac K, Wang RD, Stewart J, Kaur P, et al · · 2025 · PMID 41051228 · DOI 10.1093/function/zqaf047