A Study of the Safety, Tolerability, and Pharmacokinetics of SM04690 Injectable Suspension Following Single Intradiscal Injection in Subjects With Degenerative Disc Disease

Study Overview
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Brief Summary
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SM04690-DDD-01 is a Phase 1, open-label, dose escalation study. SM04690 Injectable Suspension will be administered via a single intradiscal injection to subjects with degenerative disc disease (DDD) under fluoroscopic guidance. Groups of 6 subjects will be enrolled in successive cohorts. Subjects will participate in a 6 month follow-up period. Clinic visits will be Screening, Treatment Visit Day 1, and Follow-up Visit Days 2, 15, 28, 60, 90, 135, and 180.

Official Title
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A Phase 1, Open-label Study of the Safety, Tolerability, and Pharmacokinetics of SM04690 Injectable Suspension Following Single Intradiscal Injection in Subjects With Degenerative Disc Disease

Conditions
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Degenerative Disc Disease

Intervention / Treatment
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* Drug: SM04690


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Degenerative disease in a maximum of two and a minimum of one lumbar disc (L4/L5 or L5/S1) Persistent low back pain due to DDD for at least 3 months prior to study start Full understanding of the requirements of the study and willingness to comply with all study visits and assessments Subjects must have read and understood the informed consent form, and must have signed it prior to any study-related procedure being performed Exclusion Criteria: Women who are pregnant, lactating, or have a positive pregnancy result at study start Women of child bearing potential who are sexually active and are not willing to use a highly effective method of birth control during the study period Males who are sexually active and have a partner who is capable of becoming pregnant, neither of whom have had surgery to become sterilized or whom are not using a highly effective method of birth control Body mass index (BMI) > 35 Previous participation in a Samumed clinical trial investigating SM04690 History of compression fractures and/or osteoporosis Any herniation in the lumbar spine as identified by MRI Congenital or acquired diseases leading to spine deformations History of hypersensitivity or allergies to any ingredient of the study medication Participation in a clinical research trial that included the receipt of an investigational product or any experimental therapeutic procedure, or an observational research trial related to DDD within 8 weeks prior to any study injection, or planned participation in any such trial; the last date of participation in the trial, not the last date of receipt of investigational product, must be at least 8 weeks prior to study start Poor peripheral venous access Any contraindications to MRI according to MRI guidelines History of malignancy; however, subjects with prior history of in situ cancer or basal or squamous cell skin cancer, completely cured, are eligible. Any diagnosed psychiatric condition that includes, but is not limited to, a history of mania, bipolar disorder, psychotic disorder, schizophrenia, schizoaffective disorder, major depressive disorder, or generalized anxiety disorder Prior surgical procedures (e.g., discectomy, intradiscal electrothermal therapy, intradiscal radiofrequency, artificial disc replacement, and interbody fusion) on the lumbar spine Any planned or elective surgery during the study period Any known active infections, including hepatitis B or hepatitis C infection, and/or infections that may compromise the immune system such as human immunodeficiency virus (HIV) Current or prior history of any spinal infection (i.e., discitis, septic arthritis, or epidural abscess) Any lumbar intradiscal injection procedure (e.g., injection of corticosteroids, methylene blue, dextrose, etc.), myelograms, discography, and/or lumbar epidural or transforaminal injections with corticosteroids or nerve-blocking anesthetics (e.g, lidocaine, bupivacaine) within 3 months prior to study start Any electrotherapy (i.e., transcutaneous electrical nerve stimulation [TENS] unit) or acupuncture for DDD within 4 weeks prior to study medication injection History of or current/pending disability claim, workers' compensation, or litigation(s) related to back pain/injury Subjects who are immediate family members (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study at any investigative site, or are directly affiliated with the study at any investigative site Subjects employed by Samumed, LLC, or any of its affiliates or development partners (that is, an employee, temporary contract worker, or designee) responsible for the conduct of the study, or who are immediate family members (spouse, parent, child, or sibling; biological or legally adopted) of said employees responsible for the conduct of the study

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.03mg SM04690<br>0.03mg SM04690 per 0.5 mL intradiscal injection (single injection at Day 1) | Drug: SM04690<br>* suspension formulation of SM04690, delivered via intradiscal injection (single injection)<br>|
| Experimental: 0.07mg SM04690<br>0.07mg SM04690 per 0.5 mL intradiscal injection (single injection at Day 1) | Drug: SM04690<br>* suspension formulation of SM04690, delivered via intradiscal injection (single injection)<br>|
| Experimental: 0.15mg SM04690<br>0.15mg SM04690 per 0.5 mL intradiscal injection (single injection at Day 1) | Drug: SM04690<br>* suspension formulation of SM04690, delivered via intradiscal injection (single injection)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability: treatment emergent adverse events (TEAEs) | Evaluate the safety and tolerability of SM04690 Injectable Suspension as measured by TEAEs during the entire treatment and observation period | Day 180 | 
| Safety and tolerability: change from baseline in electrocardiogram (ECG) parameters | Evaluate the safety and tolerability of SM04690 Injectable Suspension as measured by change from baseline in ECG parameters | Baseline and Day 180 | 
| Safety and tolerability: change from baseline in physical examination | Evaluate the safety and tolerability of SM04690 Injectable Suspension as measured by change from baseline in physical examination (number of subjects with clinically significant change in physical examination) | Baseline and Day 180 | 
| Safety and tolerability: change from baseline in clinical laboratory tests | Evaluate the safety and tolerability of SM04690 Injectable Suspension as measured by change from baseline in clinical laboratory tests (number of subjects with clinically significant changes in laboratory test parameters) | Baseline and Day 180 | 
| Safety and tolerability: change from baseline in vital signs | Evaluate the safety and tolerability of SM04690 Injectable Suspension as measured by change from baseline in vital signs (number of subjects with clinically significant changes in vital signs) | Baseline and Day 180 | 
| Incidence of dose-limiting toxicities (DLTs) | Evaluate incidence and severity of DLTs in each cohort | Day 180 | 
| Pharmacokinetics (PK) of SM04690: Cmax | Maximum plasma concentration (Cmax) estimate for a single intradiscal injection of SM04690 Injectable Suspension | Day 1 | 
| PK of SM04690: tmax | Time to Cmax estimate for a single intradiscal injection of SM04690 Injectable Suspension | Day 1 | 
| PK of SM04690: AUC | Area under the plasma-concentration time curve (AUC) estimate for a single intradiscal injection of SM04690 Injectable Suspension | Day 1 | 
| PK of SM04690: half-life | Plasma terminal phase half-life estimate for a single intradiscal injection of SM04690 Injectable Suspension | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in spine bone mineral density | Evaluate change from baseline spine bone mineral density as measured by dual-energy x-ray absorptiometry (DXA) | Baseline and Day 180 | 
| Change in hip bone mineral density | Evaluate change from baseline hip bone mineral density as measured by DXA | Baseline and Day 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SM04690, Wnt pathway, Samumed