Allogeneic Mitochondria (PN-101) Transplantation for Refractory Polymyositis or Dermatomyositis

NCT04976140 | Completed Phase 1

• 1 other identifier: PN-101-101
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 3

Brief Summary

To determine the maximum tolerated dose (MTD) based on the safety and tolerability after single-dose administration of PN-101 in patients with refractory polymyositis or dermatomyositis. To explore the efficacy after single-dose administration of PN-101 in patients with refractory polymyositis or dermatomyositis.

Conditions

Polymyositis; Dermatomyositis

Keywords

mitochondria

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity(DLT)

  Assessment of DLT for each dose group up to 2 weeks after the IP administration. Severity will be graded according to CTCAE, Version 5.0.

  2 weeks after IP administration

• International Myositis And Clinical Studies group-Total Improvement Score(IMACS-TIS)

  Assessment of IMACS-TIS at Week 12 after the IP administration. Total Improvement Score (TIS) based on absolute percentage change is assessed scale 0 to 100. Higher score indicates greater improvement.

  12 weeks after the IP administration

Secondary Outcomes (6)

• International Myositis And Clinical Studies group-Total Improvement Score(IMACS-TIS)

  4 weeks after the IP administration

• International Myositis And Clinical Studies group-Total Improvement Score(IMACS-TIS)

  8 weeks after the IP administration

• Response rate of IMACS-TIS

  12 weeks after the IP administration

• Changes of Core Set Activity Measures(CSAM)

  Visit 2(Day 1), Visit 5(4 weeks), Visit 6(8 weeks), Visit 7(12 weeks)

• Changes of Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)

  Visit 2(Day 1), Visit 5(4 weeks), Visit 6(8 weeks), Visit 7(12 weeks)

Study Arms (3)

Low dose group

EXPERIMENTAL

The investigational product is intravenously administered according to the planned dose.

Biological: PN-101

Intermediate dose group

EXPERIMENTAL

The investigational product is intravenously administered according to the planned dose.

Biological: PN-101

High dose group

EXPERIMENTAL

The investigational product is intravenously administered according to the planned dose.

Biological: PN-101

Interventions

PN-101 BIOLOGICAL

PN-101: Mitochondria isolated from Allogeneic Umbilical Cord-derived Mesenchymal Stem Cells. 3 or 6 subjects are enrolled in each dose group in line with the traditional 3+3 rule-based method, and the investigator intravenously administers a single-dose of the investigational product according to the planned dose.

High dose group; Intermediate dose group; Low dose group

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult aged 19 years or more
• A subject who is diagnosed with polymyositis or dermatomyositis and satisfies all of the followings
• Clinical profile: Slowly progressing clinical profile with symmetrical and apparent muscular weakness confirmed at the proximal muscle (in case of dermatomyositis, clinical findings related with characteristic skin symptoms\*)
• \* Gottron's papules or sign, erythema purpura, poikiloderma, calcinosis cutis, etc.
• Serum test: Serum creatine kinase (CK) elevated (CK ≥ 1.3 × upper limit of normal (ULN)) or serum myositis-specific antibodies (MSA) positive
• Electromyography (EMG): Presence of a finding that indicates myopathy
• Baseline (prior to the investigational product administration) manual muscle testing-8 (MMT-8) result \< 125/150 (bilaterally), and at least 2 of the following International Myositis and Clinical Studies Group (IMACS) core set results
• Physician global disease activity \[visual analogue scale (VAS)\] ≥ 2 cm
• Patient global disease activity \[VAS\] ≥ 2 cm
• Health assessment questionnaire (HAQ) disability assessment ≥ 0.25
• or more items with the serum muscle enzyme \> 1.3 × ULN
• Global extramuscular disease activity \[VAS\] \> 1 cm
• A subject with the drug treatment history of polymyositis or dermatomyositis for ≥ 8 weeks, who cannot receive the conventional treatment due to being refractory or for a side effect and adverse event, and has received glucocorticosteroids at an intermediate dose (prednisone 0.5 mg/kg/day or equivalent) or higher for at least 4 weeks alone or in combination
• A subject who fully understands the trial and provided voluntary written consent to take part in the trial

You may not qualify if:

• A subject with clear muscular damage, with the VAS-based myositis damage index (MDI) of ≥ 5 at screening
• A subject with the following medical history or surgical history
• A surgical operation history within 12 weeks of screening
• Malignant tumor within 5 years of screening (excluding a subject who passed 3 years or more from complete recovery of cervical cancer or skin squamous cell carcinoma)
• A patient with severe respiratory muscular weakening or interstitial pulmonary disease (a patient who has no moderate or severe dyspnea and has stable interstitial pneumonia may participate)
• A patient with the following comorbidity at screening
• Acute viral infection or severe infection
• Active hepatitis B (e.g.: HBsAg positive and HBV DNA detected) or hepatitis C (e.g.: Anti-HCV positive and HCV RNA \[qualitatively\] detective)
• Human Immunodeficiency virus (HIV) positive
• Autoimmune disease such as rheumatoid arthritis (RA), systemic lupus erythematosus, psoriatic arthritis, etc. (however, in case of the overlap syndrome, a subject may participate if diseases other than inflammatory myositis are stable and myositis is thought to be due to inflammatory myositis.)
• Findings of cardiac disorder such as moderate or severe heart failure (New York Heart Association Class III/IV) or QT corrected interval prolonged
• Serious disease that may affect this study, at the discretion of the investigator (neurological disorder, cardiovascular disorder, uncontrolled blood pressure or diabetes, etc.)
• Hematological, renal and hepatic dysfunction based on the following laboratory findings at screening
• Glomerular filtration rate (GFR)\* \< 45 mL/min
• \*eGFR (mL/min/1.73m\^2) = 175 × (serum creatinine concentration (mg/dL))\^-1.154 × (age)\^-0.203 × (0.742 in female) \[modification of diet in renal disease (MDRD) formula\]

Sponsors & Collaborators

• Paean Biotechnology Inc.: lead

Study Sites (3)

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Soonchunhyang University Seoul Hospital

Seoul, 04401, South Korea

Location

Hanyang University Seoul Hospital

Seoul, 04763, South Korea

Location

MeSH Terms

Conditions

Polymyositis; Dermatomyositis

Condition Hierarchy (Ancestors)

Myositis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Eunyoung Lee, MD

  Seoul National University College of Medicine

  PRINCIPAL INVESTIGATOR

• Daehyun Yoo, MD

  Hanyang University College of Medicine

  PRINCIPAL INVESTIGATOR

• Hyunsook Kim, MD

  Soonchunhyang University College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2021
• First Posted: July 26, 2021
• Study Start: December 15, 2021
• Primary Completion: October 6, 2023
• Study Completion: October 6, 2023
• Last Updated: April 3, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (3)