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

Degenerative Disc Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03246399
• Other study ID #: SM04690-DDD-01
• Status: Terminated
• Phase: Phase 1
• Start date: July 26, 2017
• Est. completion date: December 4, 2018

Study information

• Verified date: April 2019
• Source: Samumed LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: December 4, 2018
• Est. primary completion date: November 14, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Degenerative Disc Disease
• Intervertebral Disc Degeneration
• Spinal Diseases

Intervention

Drug:
• SM04690
suspension formulation of SM04690, delivered via intradiscal injection (single injection)

Locations

Country	Name	City	State
United States	Research Site	Charleston	South Carolina
United States	Research Site	Richmond	Virginia
United States	Research Site	San Diego	California
United States	Research Site	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Samumed LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in lumbar back pain	Evaluate change from baseline lumbar back pain using the Visual Analog Scale (VAS)	Baseline and Day 180
Other	Change in disability	Evaluate change from baseline disability as measured by Oswestry disability index (ODI)	Baseline and Day 180
Other	Change in disease activity by physician assessment	Evaluate change from baseline disease activity using Physician Global Assessment (PGA)	Baseline and Day 180
Other	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
Other	Change in disc space height	Evaluate change from baseline in disc space height by radiograph	Baseline and Day 180
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Incidence of dose-limiting toxicities (DLTs)	Evaluate incidence and severity of DLTs in each cohort	Day 180
Primary	Pharmacokinetics (PK) of SM04690: Cmax	Maximum plasma concentration (Cmax) estimate for a single intradiscal injection of SM04690 Injectable Suspension	Day 1
Primary	PK of SM04690: tmax	Time to Cmax estimate for a single intradiscal injection of SM04690 Injectable Suspension	Day 1
Primary	PK of SM04690: AUC	Area under the plasma-concentration time curve (AUC) estimate for a single intradiscal injection of SM04690 Injectable Suspension	Day 1
Primary	PK of SM04690: half-life	Plasma terminal phase half-life estimate for a single intradiscal injection of SM04690 Injectable Suspension	Day 1
Secondary	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
Secondary	Change in hip bone mineral density	Evaluate change from baseline hip bone mineral density as measured by DXA	Baseline and Day 180