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

NCT03246399 | Terminated Phase 1 FDA Drug

• 1 other identifier: SM04690-DDD-01
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 4

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.

Conditions

Degenerative Disc Disease

Keywords

SM04690; Wnt pathway; Samumed

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (2)

• Change in spine bone mineral density

  Baseline and Day 180

• Change in hip bone mineral density

  Baseline and Day 180

Other Outcomes (5)

• Change in lumbar back pain

  Baseline and Day 180

• Change in disability

  Baseline and Day 180

• Change in disease activity by physician assessment

  Baseline and Day 180

Study Arms (3)

0.03mg SM04690

EXPERIMENTAL

0.03mg SM04690 per 0.5 mL intradiscal injection (single injection at Day 1)

Drug: SM04690

0.07mg SM04690

EXPERIMENTAL

0.07mg SM04690 per 0.5 mL intradiscal injection (single injection at Day 1)

Drug: SM04690

0.15mg SM04690

EXPERIMENTAL

0.15mg SM04690 per 0.5 mL intradiscal injection (single injection at Day 1)

Drug: SM04690

Interventions

SM04690 DRUG

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

0.03mg SM04690; 0.07mg SM04690; 0.15mg SM04690

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Biosplice Therapeutics, Inc.: lead

Study Sites (4)

Research Site

San Diego, California, 92103, United States

Location

Research Site

Charleston, South Carolina, 29406, United States

Location

Research Site

Tyler, Texas, 75701, United States

Location

Research Site

Richmond, Virginia, 23235, United States

Location

MeSH Terms

Conditions

Intervertebral Disc Degeneration

Interventions

lorecivivint

Condition Hierarchy (Ancestors)

Spinal Diseases; Bone Diseases; Musculoskeletal Diseases

Study Officials

• Yusuf Yazici, M.D.

  Biosplice Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2017
• First Posted: August 11, 2017
• Study Start: July 26, 2017
• Primary Completion: November 14, 2018
• Study Completion: December 4, 2018
• Last Updated: April 23, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)