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

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

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.

Study Overview

• Status: Terminated
• Conditions: Degenerative Disc Disease
• Intervention / Treatment: Drug: SM04690

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92103
      • Research Site
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Research Site
  • Texas
    • Tyler, Texas, United States, 75701
      • Research Site
  • Virginia
    • Richmond, Virginia, United States, 23235
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in lumbar back pain	Evaluate change from baseline lumbar back pain using the Visual Analog Scale (VAS)	Baseline and Day 180
Change in disability	Evaluate change from baseline disability as measured by Oswestry disability index (ODI)	Baseline and Day 180
Change in disease activity by physician assessment	Evaluate change from baseline disease activity using Physician Global Assessment (PGA)	Baseline and Day 180
Change in treated intervertebral discs	Evaluate change from baseline in treated intervertebral discs by modified Pfirrmann grade using Magnetic Resonance Imaging (MRI)	Baseline and Day 180
Change in disc space height	Evaluate change from baseline in disc space height by radiograph	Baseline and Day 180

Collaborators and Investigators

• Sponsor: Biosplice Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2017
• Primary Completion (Actual): November 14, 2018
• Study Completion (Actual): December 4, 2018

Study Registration Dates

• First Submitted: June 29, 2017
• First Submitted That Met QC Criteria: August 7, 2017
• First Posted (Actual): August 11, 2017

Study Record Updates

• Last Update Posted (Actual): April 23, 2019
• Last Update Submitted That Met QC Criteria: April 19, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Samumed; Wnt pathway; SM04690
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Bone Diseases; Intervertebral Disc Degeneration; Spinal Diseases; Anti-Inflammatory Agents; Lorecivivint
• Other Study ID Numbers: SM04690-DDD-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No