Clinical trial NCT03246399: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Degenerative Disc Disease
Keywords: SM04690
Wnt pathway
Samumed
Lead sponsor: Biosplice Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2017-08-11
Enrollment: 6
Sex: ALL
Minimum age (years): 25
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Safety and tolerability: treatment emergent adverse events (TEAEs)
timeFrame: Day 180
measure: Safety and tolerability: change from baseline in electrocardiogram (ECG) parameters
timeFrame: Baseline and Day 180
measure: Safety and tolerability: change from baseline in physical examination
timeFrame: Baseline and Day 180
measure: Safety and tolerability: change from baseline in clinical laboratory tests
timeFrame: Baseline and Day 180
measure: Safety and tolerability: change from baseline in vital signs
timeFrame: Baseline and Day 180
measure: Incidence of dose-limiting toxicities (DLTs)
timeFrame: Day 180
measure: Pharmacokinetics (PK) of SM04690: Cmax
timeFrame: Day 1
measure: PK of SM04690: tmax
timeFrame: Day 1
measure: PK of SM04690: AUC
timeFrame: Day 1
measure: PK of SM04690: half-life
timeFrame: Day 1
Secondary outcomes:
measure: Change in spine bone mineral density
timeFrame: Baseline and Day 180
measure: Change in hip bone mineral density
timeFrame: Baseline and Day 180
Other outcomes:
measure: Change in lumbar back pain
timeFrame: Baseline and Day 180
measure: Change in disability
timeFrame: Baseline and Day 180
measure: Change in disease activity by physician assessment
timeFrame: Baseline and Day 180
measure: Change in treated intervertebral discs
timeFrame: Baseline and Day 180
measure: Change in disc space height
timeFrame: Baseline and Day 180
Locations:
city: San Diego
country: United States
facility: Research Site
state: California
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Tyler
country: United States
facility: Research Site
state: Texas
city: Richmond
country: United States
facility: Research Site
state: Virginia
Study officials:
affiliation: Biosplice Therapeutics, Inc.
name: Yusuf Yazici, M.D.
role: STUDY_DIRECTOR
References: