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

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ClinicalTrials.gov Identifier: NCT03246399
Recruitment Status : Active, not recruiting
First Posted : August 11, 2017
Last Update Posted : August 6, 2018
Sponsor:
Information provided by (Responsible Party):
Samumed LLC

Brief 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.

Condition or disease Intervention/treatment Phase
Degenerative Disc Disease Drug: SM04690 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 26, 2017
Estimated Primary Completion Date : November 18, 2018
Estimated Study Completion Date : November 18, 2018

Resource links provided by the National Library of Medicine


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)




Primary Outcome Measures :
  1. Safety and tolerability: treatment emergent adverse events (TEAEs) [ Time Frame: Day 180 ]
    Evaluate the safety and tolerability of SM04690 Injectable Suspension as measured by TEAEs during the entire treatment and observation period

  2. Safety and tolerability: change from baseline in electrocardiogram (ECG) parameters [ Time Frame: Baseline and Day 180 ]
    Evaluate the safety and tolerability of SM04690 Injectable Suspension as measured by change from baseline in ECG parameters

  3. Safety and tolerability: change from baseline in physical examination [ Time Frame: Baseline and Day 180 ]
    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)

  4. Safety and tolerability: change from baseline in clinical laboratory tests [ Time Frame: Baseline and Day 180 ]
    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)

  5. Safety and tolerability: change from baseline in vital signs [ Time Frame: Baseline and Day 180 ]
    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)

  6. Incidence of dose-limiting toxicities (DLTs) [ Time Frame: Day 180 ]
    Evaluate incidence and severity of DLTs in each cohort

  7. Pharmacokinetics (PK) of SM04690: Cmax [ Time Frame: Day 1 ]
    Maximum plasma concentration (Cmax) estimate for a single intradiscal injection of SM04690 Injectable Suspension

  8. PK of SM04690: tmax [ Time Frame: Day 1 ]
    Time to Cmax estimate for a single intradiscal injection of SM04690 Injectable Suspension

  9. PK of SM04690: AUC [ Time Frame: Day 1 ]
    Area under the plasma-concentration time curve (AUC) estimate for a single intradiscal injection of SM04690 Injectable Suspension

  10. PK of SM04690: half-life [ Time Frame: Day 1 ]
    Plasma terminal phase half-life estimate for a single intradiscal injection of SM04690 Injectable Suspension


Secondary Outcome Measures :
  1. Change in spine bone mineral density [ Time Frame: Baseline and Day 180 ]
    Evaluate change from baseline spine bone mineral density as measured by dual-energy x-ray absorptiometry (DXA)

  2. Change in hip bone mineral density [ Time Frame: Baseline and Day 180 ]
    Evaluate change from baseline hip bone mineral density as measured by DXA


Other Outcome Measures:
  1. Change in lumbar back pain [ Time Frame: Baseline and Day 180 ]
    Evaluate change from baseline lumbar back pain using the Visual Analog Scale (VAS)

  2. Change in disability [ Time Frame: Baseline and Day 180 ]
    Evaluate change from baseline disability as measured by Oswestry disability index (ODI)

  3. Change in disease activity by physician assessment [ Time Frame: Baseline and Day 180 ]
    Evaluate change from baseline disease activity using Physician Global Assessment (PGA)

  4. Change in treated intervertebral discs [ Time Frame: Baseline and Day 180 ]
    Evaluate change from baseline in treated intervertebral discs by modified Pfirrmann grade using Magnetic Resonance Imaging (MRI)

  5. Change in disc space height [ Time Frame: Baseline and Day 180 ]
    Evaluate change from baseline in disc space height by radiograph



Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03246399


Locations
United States, California
Research Site
San Diego, California, United States, 92103
United States, South Carolina
Research Site
Charleston, South Carolina, United States, 29406
United States, Texas
Research Site
Tyler, Texas, United States, 75701
United States, Virginia
Research Site
Richmond, Virginia, United States, 23235
Sponsors and Collaborators
Samumed LLC
Investigators
Study Director: Yusuf Yazici, M.D. Samumed LLC

Responsible Party: Samumed LLC
ClinicalTrials.gov Identifier: NCT03246399     History of Changes
Other Study ID Numbers: SM04690-DDD-01
First Posted: August 11, 2017    Key Record Dates
Last Update Posted: August 6, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Samumed LLC:
SM04690
Wnt pathway
Samumed

Additional relevant MeSH terms:
Spinal Diseases
Intervertebral Disc Degeneration
Bone Diseases
Musculoskeletal Diseases