Evaluation of Efficacy, Tolerability, and Pharmacokinetics of MYMD1 for Chronic Inflammation and Sarcopenia/Frailty

NCT05283486 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: MyMD-PK-003
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief Summary

The study will be conducted to investigate the efficacy, tolerability and pharmacokinetics of MYMD1 in participants with chronic inflammation associated with sarcopenia/frailty, a condition linked to elevated levels of proinflammatory cytokines.

Conditions

Sarcopenia; Frailty; Aging

Keywords

frailty; aging; sarcopenia

Outcome Measures

Primary Outcomes (32)

• Demonstrate reduction of chronic inflammatory markers in participants treated with MYMD1

  Effect on serum levels of sTNFR1, IL-6, and TNFα over 28 days of treatment

  Screening

• Demonstrate reduction of chronic inflammatory markers in participants treated with MYMD1

  Effect on serum levels of sTNFR1, IL-6, and TNFα over 28 days of treatment

  Day 1

• Demonstrate reduction of chronic inflammatory markers in participants treated with MYMD1

  Effect on serum levels of sTNFR1, IL-6, and TNFα over 28 days of treatment

  Day 7

• Demonstrate reduction of chronic inflammatory markers in participants treated with MYMD1

  Effect on serum levels of sTNFR1, IL-6, and TNFα over 28 days of treatment

  Day 14

• Demonstrate reduction of chronic inflammatory markers in participants treated with MYMD1

  Effect on serum levels of sTNFR1, IL-6, and TNFα over 28 days of treatment

  Day 21

• Demonstrate reduction of chronic inflammatory markers in participants treated with MYMD1

  Effect on serum levels of sTNFR1, IL-6, and TNFα over 28 days of treatment

  Day 28

• To evaluate the PK of oral doses of MYMD1 capsules

  Area Under the Curve (AUC) (0-last): variation of a drug concentration in blood plasma as a function of time, compared across treatment and placebo groups.

  Cohorts 1, 2, 3, 4: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 24 hrs; Day 7, pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 24; Day 14, pre-dose, 0.5 hrs; Day 21, pre-dose, 0.5 hrs; Day 28, pre-dose, 0.5 hrs]

• To evaluate the PK of oral doses of MYMD1 capsules

  Pharmacokinetics: Cmax - Maximum Concentration of drug substance in blood plasma, compared across treatment and placebo groups.

  Cohorts 1, 2, 3, 4: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 24 hrs; Day 7, pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 24; Day 14, pre-dose, 0.5 hrs; Day 21, pre-dose, 0.5 hrs; Day 28, pre-dose, 0.5 hrs]

• To evaluate the PK of oral doses of MYMD1 capsules

  Pharmacokintetics: tmax - Time to Maximum Concentration of drug substance in blood plasma, compared across treatment and placebo groups.

  Cohorts 1, 2, 3, 4: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 24 hrs; Day 7, pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 24; Day 14, pre-dose, 0.5 hrs; Day 21, pre-dose, 0.5 hrs; Day 28, pre-dose, 0.5 hrs]

• To evaluate the PK of oral doses of MYMD1 capsules

  Pharmacokinetics: t1/2 - Time to metabolize 1/2 of dose (eg, half-life) of drug substance, measured in blood plasma, compared across treatment and placebo groups.

  Cohorts 1, 2, 3, 4: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 24 hrs; Day 7, pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 24; Day 14, pre-dose, 0.5 hrs; Day 21, pre-dose, 0.5 hrs; Day 28, pre-dose, 0.5 hrs]

• To evaluate the PK of oral doses of MYMD1 capsules

  Pharmacokinetics: CL/F - Oral Clearance of the drug substance (CL/F), compared across treatment and placebo groups.

  Cohorts 1, 2, 3, 4: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 24 hrs; Day 7, pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 24; Day 14, pre-dose, 0.5 hrs; Day 21, pre-dose, 0.5 hrs; Day 28, pre-dose, 0.5 hrs]

• To evaluate the PK of oral doses of MYMD1 capsules

  Pharmacokinetics: Volume of Distribution (V2/F ) - Volume of Distribution of the drug substance (V2/F), compared across treatment and placebo groups.

  Cohorts 1, 2, 3, 4: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 24 hrs; Day 7, pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 24; Day 14, pre-dose, 0.5 hrs; Day 21, pre-dose, 0.5 hrs; Day 28, pre-dose, 0.5 hrs]

• To evaluate the PK (urine) of oral doses of MYMD1 capsules

  urine sample collection for presence of parent drug - MYMD1

  Day 1 (predose)

• To evaluate the PK (urine) of oral doses of MYMD1 capsules

  urine sample collection for presence of parent drug - MYMD1

  Day 1 (0-4 hrs post dose)

• To evaluate the PK (urine) of oral doses of MYMD1 capsules

  urine sample collection for presence of parent drug - MYMD1

  Day 1 (4-8 hrs post dose)

• To evaluate the PK (urine) of oral doses of MYMD1 capsules

  urine sample collection for presence of parent drug - MYMD1

  Day 1(8-24hrs post dose)

• To evaluate the PK (urine) of oral doses of MYMD1 capsules

  urine sample collection for presence of parent drug - MYMD1

  Day 7 (predose)

• To evaluate the PK (urine) of oral doses of MYMD1 capsules

  urine sample collection for presence of parent drug - MYMD1

  Day 7 (0-4 hours post dose)

• To evaluate the PK (urine) of oral doses of MYMD1 capsules

  urine sample collection for presence of parent drug - MYMD1

  Day 7 (4-8 hours post dose)

• To evaluate the PK (urine) of oral doses of MYMD1 capsules

  urine sample collection for presence of parent drug - MYMD1

  Day 7 (8-24hrs post dose)

• To evaluate the PK (urine) of oral doses of MYMD1 capsules

  urine sample collection for presence of parent drug - MYMD1

  Day 14 (predose)

• To evaluate the PK (urine) of oral doses of MYMD1 capsules

  urine sample collection for presence of parent drug - MYMD1

  Day 14 (0-4 hours post dose)

• To evaluate the PK (urine) of oral doses of MYMD1 capsules

  urine sample collection for presence of parent drug - MYMD1

  Day 14 (4-8 hours post dose)

• To evaluate the PK (urine) of oral doses of MYMD1 capsules

  urine sample collection for presence of parent drug - MYMD1

  Day 14 (8-24 hours post dose)

• To evaluate the PK (urine) of oral doses of MYMD1 capsules

  urine sample collection for presence of parent drug - MYMD1

  Day 21 (predose)

• To evaluate the PK of oral doses of MYMD1 capsules

  urine sample collection for presence of parent drug - MYMD1

  Day 21 (0-4 hrs post dose)

• To evaluate the PK (urine) of oral doses of MYMD1 capsules

  urine sample collection for presence of parent drug - MYMD1

  Day 21 (4-8 hours post dose)

• To evaluate the PK (urine) of oral doses of MYMD1 capsules

  urine sample collection for presence of parent drug - MYMD1

  Day 21 (8-24 hours post dose)

• To evaluate the PK (urine) of oral doses of MYMD1 capsules

  urine sample collection for presence of parent drug - MYMD1

  Day 28 (pre dose)

• To evaluate the PK (urine) of oral doses of MYMD1 capsules

  urine sample collection for presence of parent drug - MYMD1

  Day 28 (0-4hours post dose)

• To evaluate the PK (urine) of oral doses of MYMD1 capsules

  urine sample collection for presence of parent drug - MYMD1

  Day 28 (4-8 hours post dose)

• To evaluate the PK (urine) of oral doses of MYMD1 capsules

  urine sample collection for presence of parent drug - MYMD1

  Day 28 (8-24 hours post dose)

Secondary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  28 days

Study Arms (8)

Cohort 1: MYMD1 600mg

EXPERIMENTAL

Subjects randomly assigned to the MYMD1 600mg cohort

Drug: MYMD-1 600MG

Cohort 1: Placebo 600mg

PLACEBO COMPARATOR

Subjects assigned to the 600mg placebo group

Drug: placebo 600mg

Cohort 2: MYMD1 750mg

EXPERIMENTAL

Subjects randomly assigned to the MYMD1 750 cohort

Drug: MYMD-1 750mg

Cohort 2: Placebo 750mg

PLACEBO COMPARATOR

Subjects assigned to the 750mg placebo group

Drug: placebo 750mg

Cohort 3: MYMD1 900mg

EXPERIMENTAL

Subjects randomly assigned to the MYMD1 900mg cohort

Drug: MYMD-1 900mg

Cohort 3: Placebo 900mg

PLACEBO COMPARATOR

Subjects assigned to the 900mg placebo group

Drug: placebo 900mg

Cohort 4: MYMD1 1050mg

ACTIVE COMPARATOR

Subjects randomly assigned to the MYMD1 1050mg cohort

Drug: MYMD-1 1050mg

Cohort 4: Placebo group 1050mg

PLACEBO COMPARATOR

Subjects assigned to the 1050mg placebo group

Drug: placebo 1050mg

Interventions

MYMD-1 600MG DRUG

Cohort 1: 600mg drug

Also known as: MYMD1 600mg

Cohort 1: MYMD1 600mg

MYMD-1 750mg DRUG

Cohort 2: 750mg drug

Also known as: MYMD1 750mg

Cohort 2: MYMD1 750mg

MYMD-1 900mg DRUG

Cohort 3: 900mg drug

Also known as: MYMD1 900mg

Cohort 3: MYMD1 900mg

MYMD-1 1050mg DRUG

Cohort 4: 1050mg drug

Also known as: MYMD1 1050mg

Cohort 4: MYMD1 1050mg

placebo 600mg DRUG

Cohort 1: 600mg placebo

Also known as: placebo-600mg

Cohort 1: Placebo 600mg

placebo 750mg DRUG

Cohort 2: 750mg placebo

Also known as: placebo-750mg

Cohort 2: Placebo 750mg

placebo 900mg DRUG

Cohort 3: 900mg placebo

Also known as: placebo-900mg

Cohort 3: Placebo 900mg

placebo 1050mg DRUG

Cohort 4: 1050mg placebo

Also known as: placebo-1050mg

Cohort 4: Placebo group 1050mg

Eligibility Criteria

• Age: 65 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Aged 65 years or older, at the time of signing the ICF
• Type of Participant and Disease Characteristics
• Elevated biomarkers of inflammation (serum IL-6 level ≥2.5 pg/mL and/or sTNFR1 level ≥1500 pg/mL)
• Low gait speed ≤ 0.8 m/s
• Short Physical Performance Battery (SPPB) score ≤8
• Weight
• Body weight ≥35 kg Other
• Adequate dietary intake
• Able to complete a 4-meter timed walk
• Assessment and documentation of sarcopenia-related loss of muscle mass based on Dual-energy X-ray absorptiometry (DXA) -derived appendicular skeletal muscle mass index (ASMI) measurements.
• Reproductive Status
• Male participants who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
• Female participants are eligible to participate if they do not qualify as a woman of childbearing potential (WOCBP)
• Informed Consent
• Capable of giving signed informed consent as described in Appendix 2, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol

You may not qualify if:

• Taking anti-inflammatory drugs on a daily basis. Note: If the participant has been stable on their antidepressant regimen for at least 3 months and agrees not to increase the medicine for the 28 days of treatment in the trial, they may be allowed into the study
• Currently tobacco users or those who used tobacco within 30 days of study entry
• Dementia, encephalopathy or any medical condition impacting cognition
• Medical conditions that would impact mobility testing or handgrip strength including
• Rheumatoid arthritis, any autoimmune condition, Parkinson's disease, muscular dystrophy, cerebral vascular accident, lower or upper extremity neuropathy, major skeletal joint deformity, upper extremity joint dysfunction, partial or complete upper extremity amputation or missing anatomy impacting grip, history of pain with walking, gout, chronic obstructive pulmonary disease, congestive heart failure, exercise induced angina, lower extremity amputation (partial or complete) or missing anatomy impacting walking, recent surgery or hospitalization (past 3 months); lower or upper extremity fracture in the past 6 months, lower or upper extremity tendinitis, diagnosis of cancer other than basal cell carcinoma, dialysis dependent renal disease, Meniere's disease, spinal cord fracture or compression, paraplegia or quadriplegia or any other medical condition that in the opinion of the Investigator would impair measurement of a 6-minute walk or handgrip strength
• A lower limb fracture in the past 6 months or any impairment or disease severely affecting gait (eg, stroke with hemiparesis, myasthenia gravis, Parkinson's disease, peripheral polyneuropathy, intermittent claudication in advanced peripheral vascular disease, spinal stenosis, or severe osteoarthritis of the knee or hip with ineffective pain management)
• Requires regular assistance from another person for general activities of daily living (eg, bathing, dressing, toileting)
• History of cardiac conduction abnormalities, arrhythmias, and/or bradycardia
• Intraocular surgery and laser procedures for refractive correction within 6 months prior to screening
• Any underlying muscle disease including active myopathy or muscular dystrophy
• Confirmed diagnosis of heart failure classified as New York Heart Association Class III or IV (eg, dilated cardiomyopathy)
• Type I diabetes or uncontrolled Type 2 diabetes
• Chronic kidney disease (estimated glomerular filtration rate \[eGFR\] \<60 mL/min)
• History of confirmed chronic obstructive pulmonary disease with a severity Grade \>2 on the Medical Research Council Dyspnea Scale
• Confirmed rheumatoid arthritis or other systemic autoimmune disease requiring immunosuppressive therapy or corticosteroids \>10 mg/day prednisone equivalent

Sponsors & Collaborators

• TNF Pharmaceuticals, Inc.: lead

Study Sites (3)

Clinical Research of West Florida, Inc

Clearwater, Florida, 33765, United States

Location

Clinical Research of West Florida

Tampa, Florida, 33606, United States

Location

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Sarcopenia; Frailty

Interventions

isomyosmine

Condition Hierarchy (Ancestors)

Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pathologic Processes

Study Officials

• Leonard Dunn, MD

  Clinical Research of West Florida

  PRINCIPAL INVESTIGATOR

• Lon Lynn, DO

  Clinical Research of West Florida

  PRINCIPAL INVESTIGATOR

• Jeremy Walston, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind clinical trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2022
• First Posted: March 17, 2022
• Study Start: February 1, 2022
• Primary Completion: June 7, 2023
• Study Completion: June 7, 2023
• Last Updated: October 30, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)