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

  • STATUS
    Recruiting
  • End date
    Dec 31, 2022
  • participants needed
    152
  • sponsor
    Helixmith Co., Ltd.
Updated on 20 July 2022
diabetes
gabapentin
pregabalin
hemoglobin a1c
glycosylated hemoglobin
peripheral neuropathy
diabetic peripheral neuropathy

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.

Description

Overall Design VMDN-003-2 is an adaptive Phase 3, double-blind, randomized, placebo-controlled, multicenter study designed to assess the efficacy and safety of Engensis (containing the active pharmaceutical ingredient VM202) in Participants with painful DPN. Following completion of the informed consent process, Screening activities (during 45 days [from Day -52 to Day -7] prior to Day 0) will determine which Participants meet all-but-one eligibility criteria, which are assessed by an adjudication procedure, followed by completion of a 7-day eDiary prior to Day 0. Eligible participants will be enrolled and randomly assigned in a double-blind fashion and in a 1:1 ratio on Day 0 to either Engensis or Placebo. During Screening, medical history and familial cancer history, demographics, vital signs, height, body mass index (BMI), waist size, physical examination, retinal fundoscopy (by an ophthalmologist), 12-lead electrocardiogram (ECG), ultrasound of the right and left gastrocnemius muscles (to guide IM Study Injections), laboratory assessments, estimated glomerular filtration rate (eGFR), HBA1c levels, viral screening, a record of all concomitant medications and procedures, urine drug analysis, and urine pregnancy test for females of childbearing potential will be conducted. In addition, the following procedures will be conducted during Screening: Hospital Anxiety and Depression Scale (HADS), Accurate Pain Reporting (APR) and Placebo Response Reduction (PRR), Michigan Neuropathy Screening Instrument (MNSI), and cancer screening tests.

During 7 days before Day 0 and randomization, Participants must complete the full Brief Pain Inventory for Diabetic Peripheral Neuropathy (BPI-DPN) on an eDiary for determining the Average Daily Pain Scores (ADPSs) for at least 5 out of the 7 days. Adverse event (AE) assessments will start upon completion of the consent process at the start of Screening.

At any time prior to dosing on Day 0, Bedside Sensory Testing (BST) should be administered.

Following randomization, and prior to the first IM injections of Engensis or Placebo on Day 0, the partial BPI-DPN, , and quality of life instruments will be completed. Blood will be collected for testing of selected cytokines, anti-HGF antibodies, and laboratory assessments.

All Participants will receive sixteen (16) 0.5-mL IM injections of Engensis or Placebo in each calf gastrocnemius muscle at each of two Visits during two Treatment Cycles: Treatment Cycle 1 on Day 0 and Day 14, and Treatment Cycle 2 on Day 90 and Day 104. At 2 hours (± 1 hour) after completion of IM injections of Engensis or Placebo on Days 0 and 14 and Days 90 and 104, vital signs and blood draw for cytokine levels will be performed. Treatment-emergent adverse event (TEAE) assessment, including injection site reactions, will start as of randomization (Day 0) and continue throughout the study. Follow-up Study Visits will be conducted on Days 28, 60, 150, and 180 or early termination (ET). Vital signs will be recorded at all Study Visits. At the Day 180 Visit (end of study), the following assessments will be conducted: the full BPI-DPN (performed for 7 days prior to the Day 180 Visit), MNSI, BST, Patient Global Impression of Change (PGIC), and the quality of life assessments (36-item Short Form Health Survey [SF-36] and EuroQol Health Utilities Index [EQ-5D]), urine drug analysis, retinal fundoscopy, physical examination, concomitant medications and procedures, and anti-HGF antibodies. Blood will be drawn for determination of serum chemistry, lipid profile, pregnancy status, hematology, and HbA1c levels. The purpose of this study is to assess the efficacy and safety of Engensis compared to Placebo as measured by changes in the means of the Average Daily Pain Scores (ADPSs) of the full BPI-DPN, selected blood cytokines, BST, and assessments of injection site reactions, physical examination, laboratory assessments, vital signs, TEAEs, and serious adverse events (SAEs).

Study and Treatment Duration:

Screening will occur up to 52 days prior to Baseline (Day 0) and Participants will be followed from Day 0, the day of first Study Injections, to Day 180/ET.

Visit Frequency:

Consented Participants will be seen and evaluated for enrollment during Screening (up to 52 days prior to Baseline, Day 0). There are 8 visits to the Clinical Site during the study from Day 0 to Day 180 for Study Injections and follow-up.

Intervention Groups and Duration:

Two treatment groups of Participants (Engensis or Placebo) will be in the study for 180 days.

Number of Participants (N = 152 to approximately 250):

The target sample size is a minimum of 152 Participants and the maximum sample size is 250 Participants based on the proposed adaptive design analysis. The final sample size of Participants to be enrolled and evaluated will be determined by the independent Data Monitoring Committee (DMC). An interim analysis will be conducted after approximately 50% of Participants in the target sample (i.e., 76 Participants) have completed the primary efficacy endpoint at Day 180 or have withdrawn prematurely. The DMC will make a recommendation based on an unblinded (comparative) power analysis.

Details
Condition Diabetic Neuropathy, Painful
Treatment Placebo, Engensis
Clinical Study IdentifierNCT04469270
SponsorHelixmith Co., Ltd.
Last Modified on20 July 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Male or female participants age ≥ 18 years at time of completion of the informed consent process
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
Glycosylated hemoglobin A1c (HbA1c) of ≤ 10.0% using the first assessment collected during Screening
Documented diagnosis of bilateral painful DPN in both lower extremities at least 6 months prior to Screening
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)
The physical examination component of the Michigan Neuropathy Screening Instrument (MNSI) score of ≥ 2.5
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
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
Male participants must not donate sperm during the study
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
Capable and willing to comply with the requirements and restrictions of the protocol and informed consent form
Able to complete all screening activities within 45 days of signing the informed consent form

Exclusion Criteria

Other sources of pain that would prevent accurate assessment of DPN pain (e.g., thoracic and/or lumbar root proximal neuropathy, mononeuritis multiplex)
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
Has taken gabapentin or pregabalin during 30 days before completion of informed consent process or will take at any time during the study
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
Symptomatic peripheral artery disease (PAD) or PAD requiring revascularization and/or that may interfere with the conduct of the study
Vasculitis, such as from Buerger's or other disease
Hyperlipidemia or dyslipidemia not being treated with an optimal treatment regimen that follows the Standards of Care for hyperlipidemic/dyslipidemic patients with DM
Systolic blood pressure >180 mm Hg on tolerable doses of standard antihypertensive medications at Screening determined by the Investigator to preclude participation
Class 3 or 4 heart failure
Symptomatic bradycardia or untreated high degree atrioventricular block
Stroke or cerebrovascular accident or myocardial infarction within 3 months before Screening
eGFR < 30 mL/min/1.73 m2
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
Ophthalmologic conditions pertinent to signs or symptoms of proliferative diabetic retinopathy (PDR) or other ocular conditions that preclude standard ophthalmologic examination
Myopathy (e.g., Duchenne or Becker muscular dystrophy, polymyositis)
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
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)
Chronic inflammatory or autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis)
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
Participants requiring chronic oral or injectable steroids and unwilling to refrain from taking these drugs for the duration of the study
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
Positive human immunodeficiency virus (HIV) or human T-cell lymphotropic virus (HTLV) I/II test at Screening
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
Active acute or chronic hepatitis B
Participants with a prior history of stem cell transplant for cancer no matter how long they have been cancer-free
Active hepatitis C
Clinically significant laboratory values or current medical conditions during Screening that, in the judgment of the Investigator, should be exclusionary
Hospital Anxiety and Depression Scale (HADS) score of ≥ 15 on either subscale
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
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
opioids
skeletal muscle relaxants
transcutaneous electrical nerve stimulation (TENS)
acupuncture
benzodiazepines (other than stable bedtime dose)
injectable or oral steroids
Participants not on a stable dose and not willing to remain on a stable dose during
antidepressants
the study for the following drugs
antiepileptics
duloxetine
capsaicin
anesthetic creams (except during Study Injections)
Participants currently using the following medications and unwilling to discontinue
anesthetic patches
topical use on the lower legs and feet and throughout the study
ISDN spray
Recent treatment for COVID-19 with ongoing sequelae
Use of an investigational drug or treatment in past 30 days or previous participation
in a clinical study with Engensis
Body mass index (BMI) ≥ 42 kg/m2
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