Safety, Tolerability, and Effectiveness of Intramuscular Injection of CELZ-201-DDT for the Treatment of Chronic Lower Back Pain

This study is a double-blinded, randomized, placebo-controlled, dose escalation Phase 1/2a study. The objective is to determine the safety, tolerability, and efficacy of CELZ-201-DDT administered as an intramuscular injection for the treatment of lower back pain in patients with Degenerative Disc Disease. Subjects who meet all criteria for inclusion will be enrolled and randomized into either low, medium, high, or expanded high dose of CELZ-201-DDT versus Placebo, with a total of 45 subjects enrolled. Dosing cohorts I-III will contain ten subjects (n=10), with eight subjects (n=8) receiving the investigational product and two subjects (n=2) randomized to receive placebo. Dosing cohort IV will contain fifteen subjects (n=15), with ten subjects (n=10) receiving the investigational product and five subjects (n=5) randomized to receive placebo. Each subject will receive six paraspinal intramuscular injections (three injections per side) of either CELZ-201-DDT or placebo into the lumbar musculature under direct ultrasound guidance.

Inclusion criteria

• Ability of participant to understand and the willingness to sign a written informed consent document.
• Between 18-80 years of age and may be of either gender or any race.
• Subjects must have failed at least two standard of care (SOC) therapies before being enrolled in the study: 1) exercise/physical therapy; 2) oral analgesic including nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; 3) skeletal muscle relaxants. Subjects must have tried each SOC therapy for at least 3 months before failure is determined.
• Patients must have failed the SOC therapies within 12 months of enrollment in the clinical trial.
• Proof for one of the following tests already performed in the clinical care of the patient for lower back pain: 1) MRI scan demonstrating at least one disc level with grade II or greater disc degeneration using the Pfirrmann grading system; 2) Oswestry Disability Index for Back Pain score of 21-80%; 3) Visual Analogue Scale for pain of >5 on a scale of 0-10.
• Female subjects must not be breast feeding and must have no intention to become pregnant during the study, and she is using contraceptive drugs or devices.
• Any male subject must agree to use contraceptives and not donate sperm during the study.
• Subjects may be on stable opioids, narcotics, or muscle relaxants for ≥30 days before screening.

Exclusion criteria

• History of cancer in the last five years.
• Spinal infections and spinal tumors.
• Renal insufficiency requiring dialysis or an eGFR of less than 60 mL/min/1.73m2.
• ALT, AST greater than 2 times or Total Bilirubin 1.5 times the upper limit of the normal range.
• Positive pregnancy test.
• History of blood cell diseases.
• Uncontrolled diabetes mellitus - HgA1c >8%.
• Uncontrolled hypertension defined as a systolic blood pressure of >140 mmHg or diastolic blood pressure of >90 mmHg at the time of screening. If subjects have their hypertension appropriately treated, then they would be eligible to enroll.
• Patients known to have any active infection, including infection of the injection site(s), and/or any active systemic or local infection.
• Patients on chronic immunosuppressive transplant therapy. Patients receiving <5 mg of Prednisone daily may be included.
• Subjects having a concomitant life-threatening disease in which their life expectancy is estimated to be less than 2 years.
• Recent smoking history or substance abuse (within six weeks).
• Heavy alcohol use (greater than 14 drinks per week for men or 7 drinks per week for women per NIAAA)
• Use of an investigational drug, device or product, or participation in a drug research study within a period of 30 days prior to receiving study treatment.
• Any patient who has received gene therapy in the past.
• Subjects with an average baseline MED >90 mg/day during the screening period are excluded. The average will be calculated over a 7-day time period.
• Body Mass Index (BMI) > 40 kg/m2.