Lumbar Disc HerniationPhase 3NCT03607838

SI-6603 (Condoliase) Study for Lumbar Disc Herniation (Discovery 6603 Study)

A Phase 3 study testing SI-6603 in people with Lumbar Disc Herniation, run by Seikagaku Corporation at 67 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study is to evaluate the effectiveness of a single-dose intervertebral disc injection of SI-6603 in subjects with lumbar disc herniation (LDH) Read more about this study

Who is it for?: Ages 30 to 70 years
Conditions the study is for: Lumbar Disc Herniation
What is being tested?: SI-6603
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 352 participants
Where: 67 sitesUnited States
Study dates: 7 Nov 2018to 21 Mar 2023
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 30 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subjects with single-level LDH (L4-L5 or L5-S1 (or L5-L6)) with clear, demonstrable nerve root impingement as assessed by magnetic resonance imaging (MRI) and clinical symptoms corresponding to position of the impaired nerve root.
Subjects with radiculopathy/radicular leg pain in the unilateral leg for 6 weeks or more but 1 year or less.
Subjects with positive result of Straight Leg Raise (SLR) test (≤70°) only on the ipsilateral leg having chief complaint of radiculopathy
Subjects with inadequate improvement in pain caused by LDH despite 6 weeks or more of conservative treatment.

Who cannot join

Subjects who have 2 or more lumbar disc herniations as assessed by MRI.
Subjects who have undergone a lumbar operation, lumbar percutaneous nucleotomy, or lumbar intradiscal therapies at the affected level of lumbar spine.
Subjects who have received block procedure (e.g., spinal injection, epidural injection or nerve block) for treatment of LDH, oral or injectable corticosteroids within 28 days prior to randomization.
Subjects who have received opioids or cannabis by any route of administration, local anesthesia to the back, buttock, or posterior/lateral aspects of the affected leg within 7 days prior to randomization.
Subjects with a body mass index (BMI) ≥40.
Subjects who are receiving compensation according to the Workers' Compensation Act or are involved in personal injury litigation due to a lumbar-related injury.

Trial locations and contacts

67 sites in 1 country.

City, postcode or hospital

67 sites in 1 country

United States67 sites

Augusta University - Medical College of Georgia
Augusta, Georgia, 30912
Ascension Spine and Scoliosis Center
Austin, Texas, 78731
Interventional Spine Medicine
Barrington, New Hampshire, 03825
Clinical Inquest Center Ltd
Beavercreek, Ohio, 45431
Millennium Pain Center
Bloomington, Illinois, 61704
Injury Care Research
Boise, Idaho, 83713
Boulder Neurosurgical Associates
Boulder, Colorado, 80303
Indiana Spine Group
Carmel, Indiana, 46032
New Jersey Regenerative Institute
Cedar Knolls, New Jersey, 07927
Clinical Trials of South Carolina
Charleston, South Carolina, 29406
University of Virginia Orthopaedic Spine Center
Charlottesville, Virginia, 22903
St. Louis Pain Consultants
Chesterfield, Missouri, 63017
Chicago Anesthesia Pain Specialists
Chicago, Illinois, 60657
Florida Spine Institute
Clearwater, Florida, 33765
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
HRMD Research
Dallas, Texas, 75240
META Medical Research Institute
Dayton, Ohio, 45432
Spine and Orthopedic Center
Deerfield Beach, Florida, 33441
Deland Clinical research Unit
DeLand, Florida, 32720
Science Connections, LLC
Doral, Florida, 33166
OtriMed Clinical Research
Edgewood, Kentucky, 41017
Coastal Clinical Research
Fernandina Beach, Florida, 32034
New York - Presbyterian Queens
Flushing, New York, 11355
Holy Cross Medical Group
Fort Lauderdale, Florida, 33334
Pain Medicine Associates, Inc.
Fountain Valley, California, 92708
Advanced Medical Trials
Georgetown, Texas, 78628
DBPS Research, LLC
Greenwood Village, Colorado, 80111
Drug Trials America
Hartsdale, New York, 10530
Comprehensive and Interventional Pain Management LLP
Henderson, Nevada, 89052
Coastal Clinical Research
Jacksonville, Florida, 32224
Main Line Spine
King of Prussia, Pennsylvania, 19406
University of California San Diego - Center for Pain Medicine
La Jolla, California, 92037
The Helm Center for Pain Management
Laguna Woods, California, 92637
Clinical Trials of Southwest Louisiana, LLC
Lake Charles, Louisiana, 70601
Innovative Pain Care Center
Las Vegas, Nevada, 89106
The Anand Spine Group
Los Angeles, California, 90048
VA Greater Los Angeles Healthcare System
Los Angeles, California, 90073
Samaritan Center for Medical Research
Los Gatos, California, 95032
Georgia Institute for Clinical Research, LLC
Marietta, Georgia, 30060
Genoma Research Group, Inc.
Miami, Florida, 33155
Science Connections, LLC (Kendall)
Miami, Florida, 33175
AMPM Research Clinic
Miami Gardens, Florida, 33169
Delta Clinical Research
Mobile, Alabama, 36609
West Virginia University
Morgantown, West Virginia, 26506
SC Pain & Spine Specialists
Murrells Inlet, South Carolina, 29576
Tulane University School of Medicine
New Orleans, Louisiana, 70112
Ainsworth Institute Of Pain Management
New York, New York, 10022
Medical Research International
Oklahoma City, Oklahoma, 73109
Oklahoma City Clinical Research Center
Oklahoma City, Oklahoma, 73159
Neuroscience Research Center LLC
Overland Park, Kansas, 66210
Interventional Pain Specialists
Pasadena, Texas, 77505
Virginia iSpine Physicians, P.C.
Richmond, Virginia, 23235
University of Rochester- Neuromedicine Pain Management Center
Rochester, New York, 14618
UC Davis Spine Center
Sacramento, California, 95816
JBR Clinical Research
Salt Lake City, Utah, 84107
Source Healthcare
Santa Monica, California, 90403
Swedish Pain Management
Seattle, Washington, 98122
Pain Relief Centers
St. Petersburg, Florida, 33709
Pain Relief Centers
Sun City Center, Florida, 33573
Tampa Pain Relief Center
Tampa, Florida, 33603
Florida Pain Relief Group, PLLC
Tampa, Florida, 33614
Premier Medical Associates
The Villages, Florida, 32159
ARH Research, LLC.
The Woodlands, Texas, 77382
Gershon Pain Specialists
Virginia Beach, Virginia, 23454
International Spine, Pain, and Performance Center
Washington D.C., District of Columbia, 20006
The Center for Clinical Research
Winston-Salem, North Carolina, 27103
Conquest Research
Winter Park, Florida, 32789

Other trials in United States

About this study

Official title: A Multicenter, Randomized, Double-blind, Sham-controlled, Comparative Study of SI-6603 in Subjects With Lumbar Disc Herniation (Phase 3)

This study is to evaluate the effectiveness of a single-dose intervertebral disc injection of SI-6603 in subjects with lumbar disc herniation (LDH)

Conditions: Lumbar Disc Herniation
Being tested: SI-6603, Sham injection
Keywords: Lumbar disc herniation, Radiculopathy, Sciatica, Intradiscal injection, Chemonucleolysis
Medical subject headings: Intervertebral Disc Displacement, Radiculopathy, Sciatica

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SI-6603Drug
SI-6603 will be injected into an intervertebral disc.
Sham injectionDrug
The injection will be performed without needle placement into an intervertebral disc.

Study groups in NCT03607838
Study group	Role	What they receive
SI-6603	Experimental	Condoliase: 1.25U, intradiscal injection, one time For patients in the active treatment group, a volume of 1.0 mL was administered into the intervertebral disc in a single dose. Receives: Drug: SI-6603
Sham	Sham comparator	Sham injection For patients in the control group, a solution was not prepared and the needle was not placed in the intervertebral disc. Receives: Drug: Sham injection

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline to Week 13 in Average Worst Leg Pain Score During the Past 24 Hours Over the Previous 7 Days
The primary endpoint was the change from baseline to Week 13 in average worst leg pain score during the past 24 hours over the previous 7 days, as assessed by 100 mm Visual Analog Scale (VAS). VAS is a pain assessment tool with 0 mm representing an absence of pain, and 100 mm representing the worst pain patients have ever experienced.
Measured: baseline and 13 weeks

Secondary outcomes (3)

Change From Baseline to Week 52 in Average Worst Leg Pain Score During the Past 24 Hours Over the Previous 7 Days
One of the key secondary endpoints was the change from baseline to Week 52 in average worst leg pain score during the past 24 hours over the previous 7 days, as assessed by 100 mm Visual Analog Scale (VAS). VAS is a pain assessment tool with 0 mm representing an absence of pain, and 100 mm representing the worst pain patients have ever experienced.
Measured: baseline and 52 weeks
Change From Baseline to Week 13 in Herniation Volume
One of the key secondary endpoints was change from baseline to Week 13 in herniation volume. Herniation volumes were assessed with MRI by a central imaging facility.
Measured: baseline and 13 weeks
Change From Baseline to Week 13 in Oswestry Disability Index (ODI) Score
One of the key secondary endpioints was change from baseline to Week 13 in Oswestry Disability Index (ODI) score. The ODI questionnaire is designed to provide information as to how the patient's back (or leg) pain affects their ability to manage in everyday life. A higher score on the ODI indicates a more severe disability. The final index score is calculated as a percentage, with 0% indicating no disability and 100% indicating highest disability.
Measured: baseline and 13 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Nov 201821 Mar 2023

First posted31 Jul 2018
Study start7 Nov 2018
Primary completion3 Aug 2022
Study completion21 Mar 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Lumbar Disc HerniationStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 352 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03607838
Sponsor's protocol ID: 6603 /1133
Status last verified: Jul 2025
First submitted: 24 Jul 2018
Last updated: 24 Jul 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Macadaeg KE, Kim KD, Gupta PB, Rivera J, Patel A, Chauhan K, Watanabe J, Seo T, Zucker E, Candido K. Impact of Condoliase on Health-related Quality of Life in Participants With Radicular Leg Pain Associated With Lumbar Disk Herniation: Results From a United States Phase 3 Clinical Trial. Spine (Phila Pa 1976). 2025 Jun 15;50(12):796-803. doi: 10.1097/BRS.0000000000005327. Epub 2025 Mar 11.
PubMed 40066868
Kim KD, Ahadian F, Hassanzadeh H, Rivera J, Candido K, Gershon S, Patel A, Gupta PB, Miller AE, Formoso FJ, Fuerst T, Zucker E, Seo T, Watanabe J, Matsuyama Y, Chiba K, Macadaeg KE. A phase 3, randomized, double-blind, sham-controlled trial of SI-6603 (condoliase) in patients with radicular leg pain associated with lumbar disc herniation. Spine J. 2024 Dec;24(12):2285-2296. doi: 10.1016/j.spinee.2024.08.006. Epub 2024 Aug 19.
PubMed 39168360

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Selective Nerve Root Block Versus Sham to Reduce Surgery for Lumbar Disc Herniation
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H-Reflex-Guided Direction-Sensitive Exercise Versus Standard Extension Exercise for Functional Recovery in Patients With Lumbar Disc Prolapse
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All Lumbar Disc Herniation trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Randomized, Double-blind, Sham-controlled, Comparative Study of SI-6603 in Subjects With Lumbar Disc Herniation (Phase 3)
ClinicalTrials.gov ID: NCT03607838
Acronym / sponsor ID: 6603 /1133
Conditions: Lumbar Disc Herniation
Keywords: Lumbar disc herniation, Radiculopathy, Sciatica, Intradiscal injection, Chemonucleolysis
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 352 participants (actual)
Lead sponsor: Seikagaku CorporationIndustry (pharma, biotech, devices)
Study start: 7 Nov 2018 (actual)
Primary completion: 3 Aug 2022 (actual)
Study completion: 21 Mar 2023 (actual)
First posted: 31 Jul 2018 (actual)
Results: Posted 11 Jul 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study is to evaluate the effectiveness of a single-dose intervertebral disc injection of SI-6603 in subjects with lumbar disc herniation (LDH)

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
SI-6603	Experimental	Drug: SI-6603Condoliase: 1.25U, intradiscal injection, one time For patients in the active treatment group, a volume of 1.0 mL was administered into the intervertebral disc in a single dose.
Sham	Sham comparator	Drug: Sham injectionSham injection For patients in the control group, a solution was not prepared and the needle was not placed in the intervertebral disc.

Who may qualify

Ages: 30 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Subjects with single-level LDH (L4-L5 or L5-S1 (or L5-L6)) with clear, demonstrable nerve root impingement as assessed by magnetic resonance imaging (MRI) and clinical symptoms corresponding to position of the impaired nerve root.
Subjects with radiculopathy/radicular leg pain in the unilateral leg for 6 weeks or more but 1 year or less.
Subjects with positive result of Straight Leg Raise (SLR) test (≤70°) only on the ipsilateral leg having chief complaint of radiculopathy
Subjects with inadequate improvement in pain caused by LDH despite 6 weeks or more of conservative treatment.

Key exclusion criteria (6 listed)

Subjects who have 2 or more lumbar disc herniations as assessed by MRI.
Subjects who have undergone a lumbar operation, lumbar percutaneous nucleotomy, or lumbar intradiscal therapies at the affected level of lumbar spine.
Subjects who have received block procedure (e.g., spinal injection, epidural injection or nerve block) for treatment of LDH, oral or injectable corticosteroids within 28 days prior to randomization.
Subjects who have received opioids or cannabis by any route of administration, local anesthesia to the back, buttock, or posterior/lateral aspects of the affected leg within 7 days prior to randomization.
Subjects with a body mass index (BMI) ≥40.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SI-6603SI-6603 will be injected into an intervertebral disc.	Drug	SI-6603
Sham injectionThe injection will be performed without needle placement into an intervertebral disc.	Drug	Sham

Primary outcome

Change From Baseline to Week 13 in Average Worst Leg Pain Score During the Past 24 Hours Over the Previous 7 Days
Time frame: baseline and 13 weeks
The primary endpoint was the change from baseline to Week 13 in average worst leg pain score during the past 24 hours over the previous 7 days, as assessed by 100 mm Visual Analog Scale (VAS). VAS is a pain assessment tool with 0 mm representing an absence of pain, and 100 mm representing the worst pain patients have ever experienced.

3 secondary outcomes

Change From Baseline to Week 52 in Average Worst Leg Pain Score During the Past 24 Hours Over the Previous 7 Days
Time frame: baseline and 52 weeks
Change From Baseline to Week 13 in Herniation Volume
Time frame: baseline and 13 weeks
Change From Baseline to Week 13 in Oswestry Disability Index (ODI) Score
Time frame: baseline and 13 weeks

Results and safety

Results posted to the registry on 11 Jul 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
SI-6603	176	135
Sham	176	130

Primary outcome: Change From Baseline to Week 13 in Average Worst Leg Pain Score During the Past 24 Hours Over the Previous 7 Days

Time frame: baseline and 13 weeks. Least squares mean (Standard Error). Unit: units on a scale

Measure	SI-6603 n = 169	Sham n = 172
Value	-41.7 (2.38)	-34.2 (2.36)

SI-6603 vs Sham: Mean Difference (Final Values): -7.5 (95% CI -14.1 to -0.9), p = 0.0263, Mixed Models Analysis

Population analysed: Modified intention-to-treat population

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 52 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
SI-6603	7 of 167 (4.2%)	91 of 167 (54.5%)	1 of 167
Sham	6 of 174 (3.4%)	62 of 174 (35.6%)	0 of 174

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40066868Macadaeg KE, Kim KD, Gupta PB, Rivera J, Patel A, Chauhan K, Watanabe J, Seo T, Zucker E, Candido K. Impact of Condoliase on Health-related Quality of Life in Participants With Radicular Leg Pain Associated With Lumbar Disk Herniation: Results From a United States Phase 3 Clinical Trial. Spine (Phila Pa 1976). 2025 Jun 15;50(12):796-803. doi: 10.1097/BRS.0000000000005327. Epub 2025 Mar 11.
Derived from this study: PubMed 39168360Kim KD, Ahadian F, Hassanzadeh H, Rivera J, Candido K, Gershon S, Patel A, Gupta PB, Miller AE, Formoso FJ, Fuerst T, Zucker E, Seo T, Watanabe J, Matsuyama Y, Chiba K, Macadaeg KE. A phase 3, randomized, double-blind, sham-controlled trial of SI-6603 (condoliase) in patients with radicular leg pain associated with lumbar disc herniation. Spine J. 2024 Dec;24(12):2285-2296. doi: 10.1016/j.spinee.2024.08.006. Epub 2024 Aug 19.

Related trials for Lumbar Disc Herniation

Not yet recruiting
Effects of Spinal Mobilization With and Without Clinical Pilates in Patients With Lumbar Disc Herniationc Herniation
Disc Herniation
Enrolling by invitationObservational study
Intradiscal Ozone/Oxygen Injection for Treatment of Contained Lumbar Disc Herniation
Lumbar Disc Herniation
Not yet recruiting
Selective Nerve Root Block Versus Sham to Reduce Surgery for Lumbar Disc Herniation
Lumbar Disc Herniation, Lumbar Radiculopathy
Not yet recruiting
H-Reflex-Guided Direction-Sensitive Exercise Versus Standard Extension Exercise for Functional Recovery in Patients With Lumbar Disc Prolapse
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RecruitingObservational study
Pulmonary Mechanics and Cerebral Oxygenation During Prone Lumbar Disc Surgery
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

67 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing SI-6603 in people with Lumbar Disc Herniation, run by Seikagaku Corporation at 67 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 67 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline to Week 13 in Average Worst Leg Pain Score During the Past 24 Hours Over the Previous 7 Days (time frame: baseline and 13 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03607838, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2025.