A Study of the Safety, Tolerability, and Pharmacokinetics of SM04690 Injectable Suspension Following Single Intradiscal Injection in Subjects With Degenerative Disc Disease
Primary Purpose
Degenerative Disc Disease
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SM04690
Sponsored by
About this trial
This is an interventional treatment trial for Degenerative Disc Disease focused on measuring SM04690, Wnt pathway, Samumed
Eligibility 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
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
0.03mg SM04690
0.07mg SM04690
0.15mg SM04690
Arm Description
0.03mg SM04690 per 0.5 mL intradiscal injection (single injection at Day 1)
0.07mg SM04690 per 0.5 mL intradiscal injection (single injection at Day 1)
0.15mg SM04690 per 0.5 mL intradiscal injection (single injection at Day 1)
Outcomes
Primary Outcome Measures
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
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
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)
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)
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)
Incidence of dose-limiting toxicities (DLTs)
Evaluate incidence and severity of DLTs in each cohort
Pharmacokinetics (PK) of SM04690: Cmax
Maximum plasma concentration (Cmax) estimate for a single intradiscal injection of SM04690 Injectable Suspension
PK of SM04690: tmax
Time to Cmax estimate for a single intradiscal injection of SM04690 Injectable Suspension
PK of SM04690: AUC
Area under the plasma-concentration time curve (AUC) estimate for a single intradiscal injection of SM04690 Injectable Suspension
PK of SM04690: half-life
Plasma terminal phase half-life estimate for a single intradiscal injection of SM04690 Injectable Suspension
Secondary Outcome Measures
Change in spine bone mineral density
Evaluate change from baseline spine bone mineral density as measured by dual-energy x-ray absorptiometry (DXA)
Change in hip bone mineral density
Evaluate change from baseline hip bone mineral density as measured by DXA
Full Information
NCT ID
NCT03246399
First Posted
June 29, 2017
Last Updated
April 19, 2019
Sponsor
Biosplice Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03246399
Brief Title
A Study of the Safety, Tolerability, and Pharmacokinetics of SM04690 Injectable Suspension Following Single Intradiscal Injection in Subjects With Degenerative Disc Disease
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Terminated
Why Stopped
Study stopped due to business reasons, following full enrollment of the first dose cohort.
Study Start Date
July 26, 2017 (Actual)
Primary Completion Date
November 14, 2018 (Actual)
Study Completion Date
December 4, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biosplice Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Degenerative Disc Disease
Keywords
SM04690, Wnt pathway, Samumed
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
0.03mg SM04690
Arm Type
Experimental
Arm Description
0.03mg SM04690 per 0.5 mL intradiscal injection (single injection at Day 1)
Arm Title
0.07mg SM04690
Arm Type
Experimental
Arm Description
0.07mg SM04690 per 0.5 mL intradiscal injection (single injection at Day 1)
Arm Title
0.15mg SM04690
Arm Type
Experimental
Arm Description
0.15mg SM04690 per 0.5 mL intradiscal injection (single injection at Day 1)
Intervention Type
Drug
Intervention Name(s)
SM04690
Intervention Description
suspension formulation of SM04690, delivered via intradiscal injection (single injection)
Primary Outcome Measure Information:
Title
Safety and tolerability: treatment emergent adverse events (TEAEs)
Description
Evaluate the safety and tolerability of SM04690 Injectable Suspension as measured by TEAEs during the entire treatment and observation period
Time Frame
Day 180
Title
Safety and tolerability: change from baseline in electrocardiogram (ECG) parameters
Description
Evaluate the safety and tolerability of SM04690 Injectable Suspension as measured by change from baseline in ECG parameters
Time Frame
Baseline and Day 180
Title
Safety and tolerability: change from baseline in physical examination
Description
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)
Time Frame
Baseline and Day 180
Title
Safety and tolerability: change from baseline in clinical laboratory tests
Description
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)
Time Frame
Baseline and Day 180
Title
Safety and tolerability: change from baseline in vital signs
Description
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)
Time Frame
Baseline and Day 180
Title
Incidence of dose-limiting toxicities (DLTs)
Description
Evaluate incidence and severity of DLTs in each cohort
Time Frame
Day 180
Title
Pharmacokinetics (PK) of SM04690: Cmax
Description
Maximum plasma concentration (Cmax) estimate for a single intradiscal injection of SM04690 Injectable Suspension
Time Frame
Day 1
Title
PK of SM04690: tmax
Description
Time to Cmax estimate for a single intradiscal injection of SM04690 Injectable Suspension
Time Frame
Day 1
Title
PK of SM04690: AUC
Description
Area under the plasma-concentration time curve (AUC) estimate for a single intradiscal injection of SM04690 Injectable Suspension
Time Frame
Day 1
Title
PK of SM04690: half-life
Description
Plasma terminal phase half-life estimate for a single intradiscal injection of SM04690 Injectable Suspension
Time Frame
Day 1
Secondary Outcome Measure Information:
Title
Change in spine bone mineral density
Description
Evaluate change from baseline spine bone mineral density as measured by dual-energy x-ray absorptiometry (DXA)
Time Frame
Baseline and Day 180
Title
Change in hip bone mineral density
Description
Evaluate change from baseline hip bone mineral density as measured by DXA
Time Frame
Baseline and Day 180
Other Pre-specified Outcome Measures:
Title
Change in lumbar back pain
Description
Evaluate change from baseline lumbar back pain using the Visual Analog Scale (VAS)
Time Frame
Baseline and Day 180
Title
Change in disability
Description
Evaluate change from baseline disability as measured by Oswestry disability index (ODI)
Time Frame
Baseline and Day 180
Title
Change in disease activity by physician assessment
Description
Evaluate change from baseline disease activity using Physician Global Assessment (PGA)
Time Frame
Baseline and Day 180
Title
Change in treated intervertebral discs
Description
Evaluate change from baseline in treated intervertebral discs by modified Pfirrmann grade using Magnetic Resonance Imaging (MRI)
Time Frame
Baseline and Day 180
Title
Change in disc space height
Description
Evaluate change from baseline in disc space height by radiograph
Time Frame
Baseline and Day 180
10. Eligibility
Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yusuf Yazici, M.D.
Organizational Affiliation
Biosplice Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Research Site
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29406
Country
United States
Facility Name
Research Site
City
Tyler
State/Province
Texas
ZIP/Postal Code
75701
Country
United States
Facility Name
Research Site
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23235
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
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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