Trial Outcomes & Findings for SI-6603 (Condoliase) Study for Lumbar Disc Herniation (Discovery 6603 Study) (NCT NCT03607838)

Last Updated: 2025-07-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

352 participants

Primary outcome timeframe

baseline and 13 weeks

Results posted on

2025-07-24

Participant Flow

Sixty sites screened at least 1 subject, and 41 of these sites enrolled at least 1 subject. The first participant was enrolled in November 2018 and the last participant was enrolled in March 2022.

A total of 807 subjects were screened for enrollment. Of the 352 subjects randomized in the study, 176 were randomized to the SI-6603 group and 176 were randomized to the sham control group. Study drug was received by 169 SI-6603 subjects, and 172 subjects underwent sham control. The reasons for discontinuation from the study before injection were 'withdrawal of consent' (4), 'failure to meet randomization criteria' (3), 'other' (3) and 'physician decision' (1).

Participant milestones

Participant milestones
Measure	SI-6603 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.	Sham Sham injection For patients in the control group, a solution was not prepared, and the needle was not placed in the intervertebral disc.
Overall Study STARTED	176	176
Overall Study Injected	169	172
Overall Study Evaluated Week 13	156	155
Overall Study COMPLETED	135	130
Overall Study NOT COMPLETED	41	46

Reasons for withdrawal

Reasons for withdrawal
Measure	SI-6603 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.	Sham Sham injection For patients in the control group, a solution was not prepared, and the needle was not placed in the intervertebral disc.
Overall Study Lack of Efficacy	14	20
Overall Study Withdrawal by Subject	13	8
Overall Study Lost to Follow-up	6	11
Overall Study Adverse Event	2	2
Overall Study Physician Decision	2	0
Overall Study Failure to meet randomization criteria	1	2
Overall Study Pregnancy	1	0
Overall Study Protocol Violation	1	0
Overall Study Due to work	1	0
Overall Study Litigation	0	1
Overall Study Temperature excursion for study drug	0	1
Overall Study Change of mind	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SI-6603 n=169 Participants 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.	Sham n=172 Participants Sham injection For patients in the control group, a solution was not prepared, and the needle was not placed in the intervertebral disc.	Total n=341 Participants Total of all reporting groups
Age, Continuous	46.8 years STANDARD_DEVIATION 9.36 • n=5 Participants	45.9 years STANDARD_DEVIATION 9.84 • n=7 Participants	46.3 years STANDARD_DEVIATION 9.60 • n=5 Participants
Sex: Female, Male Female	74 Participants n=5 Participants	83 Participants n=7 Participants	157 Participants n=5 Participants
Sex: Female, Male Male	95 Participants n=5 Participants	89 Participants n=7 Participants	184 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	47 Participants n=5 Participants	43 Participants n=7 Participants	90 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	122 Participants n=5 Participants	129 Participants n=7 Participants	251 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	18 Participants n=5 Participants	14 Participants n=7 Participants	32 Participants n=5 Participants
Race (NIH/OMB) White	137 Participants n=5 Participants	142 Participants n=7 Participants	279 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Body Mass Index (BMI)	29.0 kilograms per square meter STANDARD_DEVIATION 4.92 • n=5 Participants	28.4 kilograms per square meter STANDARD_DEVIATION 4.86 • n=7 Participants	28.7 kilograms per square meter STANDARD_DEVIATION 4.89 • n=5 Participants
Smoking History Never smoked	106 Participants n=5 Participants	103 Participants n=7 Participants	209 Participants n=5 Participants
Smoking History Past smoker	34 Participants n=5 Participants	36 Participants n=7 Participants	70 Participants n=5 Participants
Smoking History Current smoker	29 Participants n=5 Participants	33 Participants n=7 Participants	62 Participants n=5 Participants
Occupation Heavy labor	39 Participants n=5 Participants	49 Participants n=7 Participants	88 Participants n=5 Participants
Occupation Light labor	130 Participants n=5 Participants	123 Participants n=7 Participants	253 Participants n=5 Participants
Days of Onset of Current Leg Pain	161.9 days STANDARD_DEVIATION 83.57 • n=5 Participants	172.2 days STANDARD_DEVIATION 79.65 • n=7 Participants	167.1 days STANDARD_DEVIATION 81.66 • n=5 Participants
Herniation Site L4-L5	70 Participants n=5 Participants	71 Participants n=7 Participants	141 Participants n=5 Participants
Herniation Site L5-S1	99 Participants n=5 Participants	101 Participants n=7 Participants	200 Participants n=5 Participants
Worst Leg Pain (VAS)	71.99 mm STANDARD_DEVIATION 9.554 • n=5 Participants	71.82 mm STANDARD_DEVIATION 9.751 • n=7 Participants	71.91 mm STANDARD_DEVIATION 9.640 • n=5 Participants
Worst Back Pain (VAS)	53.73 mm STANDARD_DEVIATION 25.250 • n=5 Participants	52.45 mm STANDARD_DEVIATION 25.261 • n=7 Participants	53.08 mm STANDARD_DEVIATION 25.227 • n=5 Participants
ODI score	48.2 percentage of disability STANDARD_DEVIATION 11.77 • n=5 Participants	49.1 percentage of disability STANDARD_DEVIATION 11.85 • n=7 Participants	48.7 percentage of disability STANDARD_DEVIATION 11.80 • n=5 Participants

PRIMARY outcome

Timeframe: baseline and 13 weeks

Population: Modified intention-to-treat population

Outcome measures

Outcome measures
Measure	SI-6603 n=169 Participants 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.	Sham n=172 Participants Sham injection For patients in the control group, a solution was not prepared, and the needle was not placed in the intervertebral disc.
Change From Baseline to Week 13 in Average Worst Leg Pain Score During the Past 24 Hours Over the Previous 7 Days	-41.7 units on a scale Standard Error 2.38	-34.2 units on a scale Standard Error 2.36

SECONDARY outcome

Timeframe: baseline and 52 weeks

Population: Modified intention-to-treat population

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.

Outcome measures

Outcome measures
Measure	SI-6603 n=169 Participants 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.	Sham n=172 Participants Sham injection For patients in the control group, a solution was not prepared, and the needle was not placed in the intervertebral disc.
Change From Baseline to Week 52 in Average Worst Leg Pain Score During the Past 24 Hours Over the Previous 7 Days	-51.2 units on a scale Standard Error 2.40	-44.7 units on a scale Standard Error 2.41

SECONDARY outcome

Timeframe: baseline and 13 weeks

Population: Modified intention-to-treat population

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.

Outcome measures

Outcome measures
Measure	SI-6603 n=169 Participants 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.	Sham n=172 Participants Sham injection For patients in the control group, a solution was not prepared, and the needle was not placed in the intervertebral disc.
Change From Baseline to Week 13 in Herniation Volume	-103.8 mm^3 Standard Error 10.74	-78.1 mm^3 Standard Error 10.79

SECONDARY outcome

Timeframe: baseline and 13 weeks

Population: Modified intention-to-treat population

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.

Outcome measures

Outcome measures
Measure	SI-6603 n=169 Participants 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.	Sham n=172 Participants Sham injection For patients in the control group, a solution was not prepared, and the needle was not placed in the intervertebral disc.
Change From Baseline to Week 13 in Oswestry Disability Index (ODI) Score	-29.6 percentage of disability Standard Error 1.38	-25.4 percentage of disability Standard Error 1.38

Adverse Events

SI-6603

Serious events: 7 serious events

Other events: 91 other events

Deaths: 1 deaths

Sham

Serious events: 6 serious events

Other events: 62 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	SI-6603 n=167 participants at risk 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.	Sham n=174 participants at risk Sham injection For patients in the control group, a solution was not prepared, and the needle was not placed in the intervertebral disc.
Infections and infestations Abdominal abscess	0.60% 1/167 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.	0.00% 0/174 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.
Infections and infestations Appendicitis	0.00% 0/167 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.	1.1% 2/174 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.
Infections and infestations COVID-19	0.60% 1/167 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.	0.00% 0/174 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.
Infections and infestations Urosepsis	0.60% 1/167 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.	0.00% 0/174 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma	0.60% 1/167 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.	0.00% 0/174 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to spine	0.60% 1/167 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.	0.00% 0/174 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.
Nervous system disorders Sciatica	0.00% 0/167 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.	1.1% 2/174 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.
Gastrointestinal disorders Intestinal obstruction	0.60% 1/167 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.	0.00% 0/174 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.
Hepatobiliary disorders Cholelithiasis	0.00% 0/167 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.	0.57% 1/174 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.
Musculoskeletal and connective tissue disorders Back pain	0.60% 1/167 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.	0.00% 0/174 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/167 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.	0.57% 1/174 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.
Renal and urinary disorders Bladder perforation	0.60% 1/167 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.	0.00% 0/174 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.
Reproductive system and breast disorders Cervical dysplasia	0.60% 1/167 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.	0.00% 0/174 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.

Other adverse events

Other adverse events
Measure	SI-6603 n=167 participants at risk 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.	Sham n=174 participants at risk Sham injection For patients in the control group, a solution was not prepared, and the needle was not placed in the intervertebral disc.
Investigations Magnetic resonance imaging spinal abnormal	28.1% 47/167 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.	9.2% 16/174 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.
Musculoskeletal and connective tissue disorders Back pain	19.2% 32/167 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.	12.6% 22/174 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.
Musculoskeletal and connective tissue disorders Pain in extremity	10.8% 18/167 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.	7.5% 13/174 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.
Investigations Spinal X-ray abnormal	7.8% 13/167 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.	1.7% 3/174 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.
Infections and infestations COVID-19	6.6% 11/167 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.	9.8% 17/174 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.
Investigations C-reactive protein increased	6.0% 10/167 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.	3.4% 6/174 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.
Musculoskeletal and connective tissue disorders Sciatica	3.6% 6/167 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.	5.2% 9/174 • 52 weeks The safety population was defined as all randomized subjects who received the study injection, analyzed according to the treatments subjects received. Two subjects who were randomized to SI-6603, received the sham. These two subjects were analyzed as part of the sham group for safety analyses.

Additional Information

General Manager, Clinical Development Department

Seikagaku Corporation

Phone: (81)3-5220-8593

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI do not make any publication of trial results without the written permission of sponsor.
Publication restrictions are in place

Restriction type: OTHER