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PolymyositisPhase 1/2NCT04976140

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

A Phase 1/2 study testing PN-101 in people with Polymyositis and Dermatomyositis, run by Paean Biotechnology Inc. at 3 sites in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 19 years and older
Conditions the study is for
Polymyositis, Dermatomyositis
What is being tested?
PN-101
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
3 sitesSouth Korea
Study dates
15 Dec 2021to 6 Oct 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 14Show fewer
  • 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
  • 1 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

Who cannot join

  • 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
Show all 30Show fewer
  • 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
  • Findings of muscular inflammation or myopathy other than the indication (inclusion body myositis (IBM), drug-induced myopathy, amyloid myopathy, myotonic dystrophy, etc.)
  • 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]
  • Hemoglobin < 10 g/dL
  • White blood cell (WBC) count < 3.0×10^9/L
  • Absolute neutrophil count (ANC) < 1.5×10^9/L (1500/mm^3)
  • Platelet count < 100×10^9/L
  • AST and ALT > 2.5 × ULN (except for the elevation due to muscle enzyme at the discretion of the investigator)
  • Alkaline phosphatase (ALP) > 2.5 × ULN
  • Total bilirubin > 1.5 × ULN (> 3 × ULN, in case of Gilbert's syndrome)
  • Thyroid stimulating hormone level exceeding the normal range (however, if the level exceeds the normal range due to the study indication at the discretion of the investigator, the subjects are allowed to enroll.)
  • A subject with a difficulty in the efficacy assessment including the muscular strength assessment during the trial
  • A subject who is determined to require prohibited concomitant treatment during the trial
  • Pregnant woman and lactating mother or woman of childbearing potential and man who is planning to have a child or not willing to practice acceptable contraception* during the trial
  • Hormonal contraception, intrauterine device or intrauterine system implant, double barrier method (use of both male condom and occlusive cap (contraceptive diaphragm or cervical cap) along with spermicide), surgical sterilization procedure/operation (vasectomy, tubal ligation, etc.)
  • Participation in other clinical trial and administration of an investigational product or application of an investigational device within 4 weeks or half-life x 5 (whichever is longer) prior to screening
  • A subject who is otherwise ineligible for this trial, at the discretion of the investigator

Trial locations and contacts

3 sites in 1 country.

South Korea3 sites

  • Seoul National University Hospital

    Seoul, 03080

  • Soonchunhyang University Seoul Hospital

    Seoul, 04401

  • Hanyang University Seoul Hospital

    Seoul, 04763

Other trials in South Korea

About this study

Official title: A Prospective, Open, Dose-escalation, Multi-center, Phase 1/2a Trial to Evaluate the Safety, Tolerability and to Explore the Efficacy of PN-101 in Patients With Refractory Polymyositis or Dermatomyositis

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.

Read the detailed description

This Phase 1/2a clinical trial involves patients diagnosed with refractory polymyositis or dermatomyositis.

The initial safety assessment is conducted, including development of DLT in subjects up to Week 2 after the investigational product administration.

[DLT assessment criteria and method]

  • Low dose or intermediate dose level
  1. No DLT developing in the initially enrolled 3 subjects (0/3): Increase the dose to the next dose group
  2. DLT developing 1 of 3 subjects (1/3): Enroll 3 additional subjects at the same dose group and then assess DLT, and ① DLT developing in 1 out of total 6 subjects (1/3+0/3; 1/6): Increase the dose to the next dose group ② DLT developing in ≥ 2 out of total 6 subjects (≥ 2/6): In case of the low dose level, the trial is discontinued without MTD determination. In case of the intermediate dose level, MTD is assessed at the low dose which is a one lower dose level
  • High dose level
  1. No DLT developing in the initially enrolled 3 subjects (0/3): Declare as the MTD
  2. DLT developing 1 of 3 subjects (1/3): Enroll 3 additional subjects at the same dose group and then assess DLT, and ① DLT developing in 1 out of total 6 subjects (1/3+0/3; 1/6): Declare as the MTD ② DLT developing in ≥ 2 out of total 6 subjects (≥ 2/6): Assess MTD at the intermediate dose which is the one lower dose level
Being tested
PN-101
Keywords
mitochondria
Medical subject headings
Polymyositis, Dermatomyositis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PN-101Biological

    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.

Study groups in NCT04976140
Study groupRoleWhat they receive
Low dose groupExperimentalThe investigational product is intravenously administered according to the planned dose.
Receives: Biological: PN-101
Intermediate dose groupExperimentalThe investigational product is intravenously administered according to the planned dose.
Receives: Biological: PN-101
High dose groupExperimentalThe investigational product is intravenously administered according to the planned dose.
Receives: Biological: PN-101

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 2 weeks after IP administration

  2. 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.

    Measured: 12 weeks after the IP administration

Secondary outcomes (6)

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

    Assessment of IMACS-TIS at week 4 after the IP administration. Total Improvement Score (TIS) based on absolute percentage change is assessed scale 0 to 100. Higher score indicates greater improvement.

    Measured: 4 weeks after the IP administration

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

    Assessment of IMACS-TIS at week 8 after the IP administration. Total Improvement Score (TIS) based on absolute percentage change is assessed scale 0 to 100. Higher score indicates greater improvement.

    Measured: 8 weeks after the IP administration

  3. Response rate of IMACS-TIS

    Proportion of subjects with the IMACS-TIS ≥ 20 at week 12 after the IP administration.

    Measured: 12 weeks after the IP administration

  4. Changes of Core Set Activity Measures(CSAM)

    Changes in CSAM for the IMACS assessed at week 4, week 8 and week 12 after the IP administration from the baseline (Visit 2).

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

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

    Changes in CDASI assessed at week 4, week 8 and week 12 after the IP administration from the baseline (Visit 2) for dermatomyositis only.

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

  6. Changes of Peak Pruritus Numeral Rating Scale(PPNRS)

    Changes in PPNRS assessed at week 4, week 8 and week 12 after the IP administration from the baseline (Visit 2) for dermatomyositis only. The intensity of pruritis is assessed on a patient reported scale 0 to 10.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jul 2021
  2. Study start15 Dec 2021
  3. Primary completion6 Oct 2023
  4. Study completion6 Oct 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04976140
Sponsor's protocol ID
PN-101-101
Status last verified
Apr 2024
First submitted
1 Jul 2021
Last updated
3 Apr 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Suh J, Lee YS. Mitochondria as secretory organelles and therapeutic cargos. Exp Mol Med. 2024 Feb;56(1):66-85. doi: 10.1038/s12276-023-01141-7. Epub 2024 Jan 4.

    PubMed 38172601

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing PN-101 in people with Polymyositis and Dermatomyositis, run by Paean Biotechnology Inc. at 3 sites in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting Toxicity(DLT) (time frame: 2 weeks after IP administration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04976140, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2024.

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