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Study to Assess Safety and Efficacy of Engensis in Painful Diabetic Peripheral Neuropathy (REGAiN-1A)

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ClinicalTrials.gov Identifier: NCT04469270
Recruitment Status : Recruiting
First Posted : July 14, 2020
Last Update Posted : November 22, 2021
Sponsor:
Information provided by (Responsible Party):
Helixmith Co., Ltd.

Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of intramuscular (IM) administration of Engensis on pain in participants with painful diabetic peripheral neuropathy (DPN) in the feet and lower legs, as compared to Placebo, as a second Phase 3, well controlled study, sufficient in supporting the efficacy and safety of Engensis.

Condition or disease Intervention/treatment Phase
Diabetic Neuropathy, Painful Biological: Engensis Other: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 152 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Adaptive, Phase 3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Assess the Safety and Efficacy of Engensis in Participants With Painful Diabetic Peripheral Neuropathy
Actual Study Start Date : October 9, 2020
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Engensis
16 (ea) 0.25mg (0.5 mL) injections in each of the right and left gastrocnemius muscles on Days 0, 14, 90, and 104.
Biological: Engensis
Intramuscular injections

Placebo Comparator: Placebo
16 0.5 mL injections in each of the right and left gastrocnemius muscles on Days 0, 14, 90, and 104.
Other: Placebo
Intramuscular injections




Primary Outcome Measures :
  1. Efficacy of Engensis compared to Placebo on painful DPN in the feet and lower legs comparing the Average Daily Pain Score from the Day 0 Visit to the Day 180 Visit on the Brief Pain Inventory for Participants with Diabetic Peripheral Neuropathy [ Time Frame: 180 days ]
    • The Brief Pain Inventory for Participants with Diabetic Peripheral Neuropathy has a minimum score of 0 and a maximum score of 10, with a higher score representing a worse outcome of more pain.


Secondary Outcome Measures :
  1. Efficacy of Engensis on the worst pain in painful DPN in the feet and lower legs by comparing the change from baseline (Day 0) in the Worst Pain score from the Brief Pain Inventory for Diabetic Peripheral Neuropathy to Day 180 compared to Placebo [ Time Frame: 180 days ]
    • The Brief Pain Inventory for Diabetic Peripheral Neuropathy (BPI-DPN) has a minimum score of 0 and a maximum score of 10, with a higher score representing a worse outcome of more pain

  2. Efficacy of Engensis on reducing pain in painful DPN in the feet and lower legs by determining a ≥ 50% reduction in the Average Daily Pain Score from baseline to Day 180 using the Brief Pain Inventory for Participants with Diabetic Peripheral Neuropathy [ Time Frame: 180 days ]
    • The Average Daily Pain Score from the Brief Pain Inventory for Participants with Diabetic Peripheral Neuropathy has a minimum score of 0 and a maximum score of 10 with a higher score representing a worse outcome of more pain

  3. Safety of Engensis in painful DPN in the feet and lower legs by comparing the incidence of adverse and serious adverse events, the incidence of injection site reactions, and the incidence of clinically significant laboratory values to Placebo [ Time Frame: 180 days ]
    • Incidence of adverse events (AEs) and serious adverse events (SAEs)
    • Incidence of injection site reactions
    • Incidence of clinically significant laboratory values

  4. To evaluate the possibility of cellular responses to Engensis [ Time Frame: 104 days ]
    • Change from baseline in the TNF-alpha, IL-1b, IFNy, IL-6, IL-4, IL-10, and IL-12p70 cytokine profile post-dose at the Day 104 visit

  5. To evaluate the possibility of humoral responses to Engensis [ Time Frame: 104 days ]
    • Presence of hepatocyte growth factor (HGF) antibodies


Other Outcome Measures:
  1. To determine whether IM administration of Engensis has the potential for disease modification by measuring the improvement in Bedside Sensory Testing at Day 180 compared to Baseline [ Time Frame: 180 days ]
    • The Bedside Sensory Testing scale has a minimum score of 0 and a maximum score of 10 with a higher score representing a better outcome

  2. To determine whether IM administration of Engensis has the potential for improving quality of life, sensation, proprioception, and deep tendon reflexes by measuring the improvement in Bedside Sensory Testing at Day 180 compared to Baseline [ Time Frame: 180 days ]
    • The Bedside Sensory Testing scale has a minimum score of 0 and a maximum score of 10 with a higher score representing a better outcome



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Male or female participants age ≥ 18 years at time of completion of the informed consent process
  2. Type 1 or 2 diabetes mellitus (DM) and on current Standards of Medical Care in Diabetes - 2020 optimal guideline-directed medical therapy in participants (including vaccine recommendations if possible), AND without unstable diabetes or significant medical problems, such as progressive end-organ disease, within 3 months of or during Screening, in the judgment of the Investigator
  3. Glycosylated hemoglobin A1c (HbA1c) of ≤ 10.0% using the first assessment collected during Screening
  4. Documented diagnosis of bilateral painful DPN in both lower extremities at least 6 months prior to Screening
  5. An Average Daily Pain Score ≥ 4 (standard deviation ≥ 0.3 and ≤ 1.5) that is completed during the 7 days prior to randomization (Day 0)
  6. The physical examination component of the Michigan Neuropathy Screening Instrument (MNSI) score of ≥ 2.5
  7. If on medication for painful DPN (other than gabapentin or pregabalin), must be on a stable dose defined as < 50% change in total dose over 3 months prior to completion of informed consent process
  8. Male participants and their female partners must agree to use double-barrier contraception during the study or provide proof of postmenopausal state (minimum 1 year) or surgical sterility
  9. Male participants must not donate sperm during the study
  10. Female participants must be nonpregnant, nonlactating, and either postmenopausal for at least 1 year, or surgically sterile for at least 3 months, or agree to use double barrier contraception from 28 days prior to randomization and/or their last confirmed menstrual period prior to study randomization (whichever is longer) until the end of the study
  11. Capable and willing to comply with the requirements and restrictions of the protocol and informed consent form
  12. Able to complete all screening activities within 45 days of signing the informed consent form

Exclusion Criteria

  1. Other sources of pain that would prevent accurate assessment of DPN pain (e.g., thoracic and/or lumbar root proximal neuropathy, mononeuritis multiplex)
  2. Peripheral neuropathy caused by a condition other than diabetes: e.g., anatomic (sciatic nerve compression), systemic (monoclonal gammopathy), metabolic (thyroid disease), and toxic (alcohol use) neuropathies
  3. Has taken gabapentin or pregabalin during 30 days before completion of informed consent process or will take at any time during the study
  4. Progressive or degenerative neurological disorder, such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, vascular dementia, multiple sclerosis, or other neurological disorders determined by the Investigator to preclude participation
  5. Symptomatic peripheral artery disease (PAD) or PAD requiring revascularization and/or that may interfere with the conduct of the study
  6. Vasculitis, such as from Buerger's or other disease
  7. Systolic blood pressure >180 mm Hg on tolerable doses of standard antihypertensive medications at Screening determined by the Investigator to preclude participation
  8. Hyperlipidemia or dyslipidemia not being treated with an optimal treatment regimen that follows the Standards of Care for hyperlipidemic/dyslipidemic patients with DM
  9. Class 3 or 4 heart failure
  10. Symptomatic bradycardia or untreated high degree atrioventricular block
  11. Stroke or cerebrovascular accident or myocardial infarction within 3 months before Screening
  12. eGFR < 30 mL/min/1.73 m2
  13. Progressive renal dysfunction, defined as a decrease in eGFR to chronic kidney disease (CKD) Stage 1, 2, or 3 in the past 6 months before Screening
  14. Ophthalmologic conditions pertinent to signs or symptoms of proliferative diabetic retinopathy (PDR) or other ocular conditions that preclude standard ophthalmologic examination
  15. Myopathy (e.g., Duchenne or Becker muscular dystrophy, polymyositis)
  16. Any prior or planned lower extremity amputation (excluding toe amputations) due to diabetic complications or prior lower leg injury (e.g., scarring, muscle atrophy) in the calf area (gastrocnemius) that would significantly reduce the surface area of the skin or amount of intact skeletal muscle required for the 16 treatment injections of Engensis
  17. Active infection requiring antimicrobial agent(s) (chronic infection or severe active infection that may compromise the Participant's well-being or participation in the study, in the Investigator's judgment)
  18. Chronic inflammatory or autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis)
  19. Immunosuppression due to underlying disease (e.g., rheumatoid arthritis, systemic lupus erythematosus) or to currently receiving immunosuppressive drugs, (e.g., chemotherapy, corticosteroids) or to radiation therapy
  20. Participants requiring chronic oral or injectable steroids and unwilling to refrain from taking these drugs for the duration of the study
  21. Participants with a family medical history of 2 or more first-degree relatives (parent, sibling, child) diagnosed to have the same type of cancer - breast cancer, cervical cancer, colon cancer, endometrial cancer, lung cancer, or prostate cancer, or with a family medical history of Lynch syndrome (hereditary non-polyposis colorectal cancer) in any first-degree relative; or who show positive results during cancer screening
  22. Positive human immunodeficiency virus (HIV) or human T-cell lymphotropic virus (HTLV) I/II test at Screening
  23. Participants who have not been cancer-free for ≥ 5 years with the following exceptions (not excluded): Participants with in-situ basal cell or squamous cell carcinoma
  24. Participants with a prior history of stem cell transplant for cancer no matter how long they have been cancer-free
  25. Active acute or chronic hepatitis B
  26. Active hepatitis C
  27. Clinically significant laboratory values or current medical conditions during Screening that, in the judgment of the Investigator, should be exclusionary
  28. Hospital Anxiety and Depression Scale (HADS) score of ≥ 15 on either subscale
  29. History of drug abuse (the habitual taking of addictive or illegal drugs) in the past 3 months and positive for Drugs of Abuse, with the exception of cannabis, during Screening
  30. Participants unwilling to discontinue their use of the following during Screening at least 7 days before starting eDiary entries and not use any of the following during the study:

    • skeletal muscle relaxants
    • opioids
    • transcutaneous electrical nerve stimulation (TENS)
    • acupuncture
    • benzodiazepines (other than stable bedtime dose)
    • injectable or oral steroids
  31. Participants not on a stable dose and not willing to remain on a stable dose during the study for the following drugs:

    • antidepressants
    • antiepileptics
    • duloxetine
  32. Participants currently using the following medications and unwilling to discontinue topical use on the lower legs and feet and throughout the study:

    • capsaicin
    • anesthetic creams (except during Study Injections)
    • anesthetic patches
    • ISDN spray
  33. Use of an investigational drug or treatment in past 30 days or previous participation in a clinical study with Engensis
  34. Body mass index (BMI) ≥ 42 kg/m2
  35. Recent treatment for COVID-19 with ongoing sequelae

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04469270


Contacts
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Contact: Jennifer Guzman 858-428-1225 ClinicalTrials@Helixmith.com

Locations
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Sponsors and Collaborators
Helixmith Co., Ltd.
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Responsible Party: Helixmith Co., Ltd.
ClinicalTrials.gov Identifier: NCT04469270    
Other Study ID Numbers: VMDN-003-2
First Posted: July 14, 2020    Key Record Dates
Last Update Posted: November 22, 2021
Last Verified: November 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Peripheral Nervous System Diseases
Diabetic Neuropathies
Pain
Neuromuscular Diseases
Nervous System Diseases
Neurologic Manifestations
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases