Clinical Trial of YH14618 in Patients With Degenerative Disc Disease

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 2b Trial to Evaluate the Efficacy and Safety of YH14618 in Patients With Lumbar Degenerative Disc Disease

Research Hypothesis:

There will be a greater proportion of VAS responders defined as those who achieve ≥ 50% reduction from baseline in VAS for low back pain at week 12 following intradiscal injection of YH14618 compared to placebo. Patients have been diagnosed as one or two symptomatic lumbar degenerative disc disease defined as Pfirrmann grade 2 to 4 using MRI. Patients have suffered from persistent low back pain with at least 3 months of conservative therapy and must have low back pain measured by VAS≥4 cm and modified Oswestry disability index (mODI) ≥30% at the baseline.

Study Overview

• Status: Completed
• Conditions: Disc Degenerative Disease
• Intervention / Treatment: Drug: Placebo; Drug: YH14618

• Study Type: Interventional
• Enrollment (Actual): 326
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Severance Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients diagnosed as one or two symptomatic early lumbar (L1/L2 ~ L5/S1) degenerative disc disease defined as Pfirrmann grade 2 to 4 using MRI performed within 4 weeks prior to randomization.
• Patients have suffered from persistent low back pain with at least 3-month conservative therapy.
• Patients have low back pain measured by VAS≥4cm and mODI≥30% at screening and randomization visit (Day 0).

Exclusion Criteria:

• Clinically significant spine compression fracture, spinal stenosis, or spinal instability.
• Clinically significant sacroiliac joint dysfunction, facet joint pain, or those who are suspected.
• Modic change type III assessed by X-ray and MRI
• History of spine surgery
• Neurologic disorders.
• Any other systemic disease which can influence spine such as rheumatoid arthritis, ankylosing spondylitis, or autoimmune disease.
• Participation in other clinical trials with intradiscal injection (eg, Phase 1/2a YH14618-201 trial, or Cell therapy, etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo group; Placebo	Drug: Placebo; Placebo matching YH14618
Experimental: Group A; YH14618 A mg/disc	Drug: YH14618
Experimental: Group B; YH14618 B mg/disc	Drug: YH14618
Experimental: Group C; YH14618 C mg/disc	Drug: YH14618
Experimental: Group D; YH14618 D mg/disc	Drug: YH14618

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of VAS responders	Proportion of VAS responders defined as those who achieve ≥ 50% reduction in VAS at week 12 from baseline	at 12-week

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of VAS responders	at 24-week
Proportion of mODI responder	at 12-week, 24-week
Changes in VAS score from baseline	Each visit for 24 weeks
Changes in mODI score from baseline	Each visit for 24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of moderate VAS responder	Moderate VAS responder are defined as those who achieve ≥ 30% reduction in VAS from baseline	at 12-week, 24-week
Percent change from baseline to Week 12 and 24 for VAS		Each visit between Week 12 and 24
Proportion of patients who are being VAS responders at Week 12 and maintain the treatment effect of ≥ 50% reduction in VAS up to week 16, 20, and 24		Each visit between Week 12 and 24
Proportion of patients who are being mODI responders at Week 12 and maintain the treatment effect of ≥ 15 points reduction in mODI up to week 16, 20, and 24		Each visit between Week 12 and 24
Change in VAS from Week 12 to Week16, 20, and 24		Each visit between Week 12 and 24
Change in mODI from Week 12 to Week 16, 20, and 24		Each visit between Week 12 and 24
Time to achieve the first ≥ 50% reduction in VAS following the intradiscal injection of Investigational product		For 24 weeks
Pfirrmann grade using MRI at Week 24		Screening, Week 24
Percent change from baseline to Week 24 for Disc Height Index (DHI)		Screening, Week 24
Quality of life measured by EQ-5D and SF-12		at Week 12 and 24
Quality of life measured by EQ-5D		at Week 12 and 24
Quality of life measured by SF-12		at Week 12 and 24
Patient global impression of change		at Week 12 and 24
Clinical global impression of change		at Week 12 and 24
Time to analgesic rescue following the intradiscal injection of Investigational product		For 24 weeks
Amount of rescue medication tablets taken following the intradiscal injection of Investigational product		For 24 weeks
The number of days taken rescue medication following the intradiscal injection of investigational product		For 24 weeks

Collaborators and Investigators

• Sponsor: Yuhan Corporation
• Investigators: Study Director: Su Youn Nam, M.D., Ph.D., Yuhan Corporation

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: December 11, 2014
• First Submitted That Met QC Criteria: December 18, 2014
• First Posted (Estimate): December 19, 2014

Study Record Updates

• Last Update Posted (Estimate): November 10, 2016
• Last Update Submitted That Met QC Criteria: November 8, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Spinal Diseases; Bone Diseases; Intervertebral Disc Degeneration
• Other Study ID Numbers: YH14618-202