A Study of SI-6603 in Patients With Lumbar Disc Herniation

• Sponsor: Seikagaku Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02421601
• Collaborator: (none)
• Enrollment: 1,011
• Locations: 48
• Arm: 1
• Duration (Months): 35.1
• Patients Per Site: 21.1
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of SI-6603(Condoliase) in patients with lumbar disc herniation.

Condition or Disease	Intervention/Treatment	Phase
Intervertebral Disc Disease; Lumbar Disc Disease	Drug: Condoliase	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1011 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-label Study of SI 6603 in Patients With Lumbar Disc Herniation (Phase III)
• Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: Feb 1, 2018
• Actual Study Completion Date: Feb 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SI-6603 SI-6603: SI-6603 is administrated into the nucleus pulposus of the intervertebral disc	Drug: Condoliase; 1.25 U, intradiscal injection, one time

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (TEAE) [26 weeks]

   A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that began or that worsened in severity after the investigational drug had been administered. All AEs, including intercurrent illnesses and regardless of the relationship to investigational drug, occurring during the study were documented from the signing of the informed consent form until completion of final visit. Concomitant illnesses, which existed before entry into the study, were not considered AEs unless they worsened during the treatment period. All AEs, regardless of the source of identification (e.g., physical examination, laboratory assessment, or reported by patient), had to be documented.

Secondary Outcome Measures

1. Worst Leg Pain as Assessed by Visual Analog Scale (VAS) [26 weeks]

   Worst leg pain intensity during the past 24 hours assessed by Visual Analog Scale (VAS). Scores are recorded by making a handwritten mark on a 100 mm line that represents a continuum between "no pain" (0 mm) and "extreme pain" (100 mm).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with lumbar disc herniation (L1-L2, L2-L3, L3-L4, L4-L5 or L5-S1) as assessed by MRI and clinical symptoms corresponding to position of the impaired nerve root.

• Patients assessed as positive in the Femoral Nerve Stretching (FNS) test for L1-L2, L2-L3, or L3-L4 and Straight Leg Raising (SLR) test.

• Patients with sciatica in either leg.

• Patients with no improvement from conservative treatment

Exclusion Criteria:

• Patients who have 2 or more lumbar disc herniations as assessed by MRI.

• Patients in whom a rupture into the posterior longitudinal ligament is identified by MRI.

• Patients who have undergone lumbar operation, or lumbar percutaneous nucleotomy or lumbar intradiscal therapies

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Mobile	Alabama	United States
2		Phoenix	Arizona	United States
3		Gold River	California	United States
4		Laguna Hills	California	United States
5		Los Gatos	California	United States
6		Riverside	California	United States
7		Temecula	California	United States
8		Greenwood Village	Colorado	United States
9		Clermont	Florida	United States
10		Hialeah	Florida	United States
11		Jacksonville	Florida	United States
12		Miami Gardens	Florida	United States
13		Miami	Florida	United States
14		Naples	Florida	United States
15		Pinellas Park	Florida	United States
16		Saint Petersburg	Florida	United States
17		Sarasota	Florida	United States
18		South Miami	Florida	United States
19		Winter Park	Florida	United States
20		Marietta	Georgia	United States
21		Newnan	Georgia	United States
22		Bloomington	Illinois	United States
23		Carmel	Indiana	United States
24		Shreveport	Louisiana	United States
25		Saint Peters	Missouri	United States
26		Hartsdale	New York	United States
27		Eugene	Oregon	United States
28		Charleston	South Carolina	United States
29		Plano	Texas	United States
30		Sandy	Utah	United States
31		Eichstätt	Bayern	Germany
32		Frankfurt	Hessen	Germany
33		Köln	Nordrhein-Westfalen	Germany
34		Göppingen	Stuttgart	Germany
35		Berlin		Germany
36		Hamburg		Germany
37		Brasov		Romania
38		Bucuresti		Romania
39		Sibiu		Romania
40		Cadiz	Andalucía	Spain
41		Palma de Mallorca	Baleares	Spain
42		Badalona	Barcelona	Spain
43		Terrassa	Barcelona	Spain
44		Valladolid	Castilla Y León	Spain
45		Alcorcón	Madrid	Spain
46		Barcelona		Spain
47		Ourense		Spain
48		Valencia		Spain

Sponsors and Collaborators

• Seikagaku Corporation

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 24, 2016

More Information

Publications

None provided.

• Responsible Party: Seikagaku Corporation
• ClinicalTrials.gov Identifier: NCT02421601
• Other Study ID Numbers: 6603/1132
• First Posted: Apr 20, 2015
• Last Update Posted: Nov 12, 2021
• Last Verified: Nov 1, 2021

• Additional relevant MeSH terms: Spinal Diseases; Intervertebral Disc Displacement

Study Results

Participant Flow

Pre-assignment Detail	Patients are enrolled in the study once eligibility is determined, but after enrollment, injection to the intervertebral disc may not be feasible due to anatomical reasons and patient condition during injection procedure. Therefore, Enrollment number in the Protocol Section (1011) and patients who Started the study (991) are not necessarily the same.

Arm/Group Title	SI-6603
Arm/Group Description	Patients received a single-dose injection of SI-6603 1.25 U into an intervertebral disc.
Period Title: Overall Study
STARTED	991
COMPLETED	909
NOT COMPLETED	82

Baseline Characteristics

Arm/Group Title	SI-6603
Arm/Group Description	Patients received a single-dose injection of SI-6603 1.25 U into an intervertebral disc.
Overall Participants	991
Age, Customized (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.1 (9.69)
Sex: Female, Male (Count of Participants)
Female	539 54.4%
Male	452 45.6%
Race/Ethnicity, Customized (Count of Participants)
Asian	4 0.4%
White	862 87%
Black	103 10.4%
Other	22 2.2%
Region of Enrollment (participants) [Number]
United States	824 83.1%
Germany	70 7.1%
Spain	75 7.6%
Romania	22 2.2%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.44 (6.172)
Leg Pain (VAS) (mm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm]	67.9 (18.48)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAE)
Description	A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that began or that worsened in severity after the investigational drug had been administered. All AEs, including intercurrent illnesses and regardless of the relationship to investigational drug, occurring during the study were documented from the signing of the informed consent form until completion of final visit. Concomitant illnesses, which existed before entry into the study, were not considered AEs unless they worsened during the treatment period. All AEs, regardless of the source of identification (e.g., physical examination, laboratory assessment, or reported by patient), had to be documented.
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

Number of Patients with at Least 1 Treatment-Emergent Adverse Event N (%)

Arm/Group Title	SI-6603
Arm/Group Description	Patients received a single-dose injection of SI-6603 1.25 U into an intervertebral disc.
Measure Participants	991
Count of Participants [Participants]	615 62.1%

2. Secondary Outcome

Title	Worst Leg Pain as Assessed by Visual Analog Scale (VAS)
Description	Worst leg pain intensity during the past 24 hours assessed by Visual Analog Scale (VAS). Scores are recorded by making a handwritten mark on a 100 mm line that represents a continuum between "no pain" (0 mm) and "extreme pain" (100 mm).
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SI-6603
Arm/Group Description	Patients received a single-dose injection of SI-6603 1.25 U into an intervertebral disc.
Measure Participants	900
Mean (Standard Deviation) [units on a scale]	28.6 (29.61)

Adverse Events

Time Frame	26 Weeks
Arm/Group Title	SI-6603
Arm/Group Description	Patients received a single-dose injection of SI-6603 1.25 U into an intervertebral disc.
All Cause Mortality
	SI-6603
	Affected / at Risk (%)	# Events
Total	4/991 (0.4%)
Serious Adverse Events
	SI-6603
	Affected / at Risk (%)	# Events
Total	36/991 (3.6%)
Cardiac disorders
Acute myocardial infarction	1/991 (0.1%)
Cardio-respiratory arrest	1/991 (0.1%)
Gastrointestinal disorders
Ascites	1/991 (0.1%)
Colitis	1/991 (0.1%)
General disorders
Non-cardiac chest pain	2/991 (0.2%)
Pain	1/991 (0.1%)
Hepatobiliary disorders
Cholecystitis	1/991 (0.1%)
Cholelithiasis	1/991 (0.1%)
Infections and infestations
Pneumonia	1/991 (0.1%)
Urinary tract infection bacterial	1/991 (0.1%)
Urosepsis	1/991 (0.1%)
Wound infection	1/991 (0.1%)
Injury, poisoning and procedural complications
Ankle fracture	2/991 (0.2%)
Road traffic accident	2/991 (0.2%)
Spinal compression fracture	1/991 (0.1%)
Toxicity to various agents	1/991 (0.1%)
Wound dehiscence	1/991 (0.1%)
Investigations
Nuclear magnetic resonance imaging abnormal	1/991 (0.1%)
Metabolism and nutrition disorders
Hyponatraemia	1/991 (0.1%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	3/991 (0.3%)
Arthralgia	1/991 (0.1%)
Back pain	1/991 (0.1%)
Osteoarthritis	1/991 (0.1%)
Pain in extremity	1/991 (0.1%)
Paraspinal abscess	1/991 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	1/991 (0.1%)
Breast cancer	1/991 (0.1%)
Hodgkin's disease recurrent	1/991 (0.1%)
Small intestine adenocarcinoma	1/991 (0.1%)
Nervous system disorders
Transient ischaemic attack	2/991 (0.2%)
Cerebral ischaemia	1/991 (0.1%)
Sciatica	1/991 (0.1%)
Syncope	1/991 (0.1%)
Psychiatric disorders
Drug dependence	1/991 (0.1%)
Panic attack	1/991 (0.1%)
Reproductive system and breast disorders
Uterine haemorrhage	1/991 (0.1%)
Respiratory, thoracic and mediastinal disorders
Asthma	2/991 (0.2%)
Chronic obstructive pulmonary disease	1/991 (0.1%)
Vascular disorders
Hypertensive crisis	1/991 (0.1%)
Other (Not Including Serious) Adverse Events
	SI-6603
	Affected / at Risk (%)	# Events
Total	615/991 (62.1%)
Gastrointestinal disorders
Nausea	15/991 (1.5%)
Infections and infestations
Nasopharyngitis	20/991 (2%)
Sinusitis	13/991 (1.3%)
Upper respiratory tract infection	10/991 (1%)
Influenza	10/991 (1%)
Investigations
Nuclear magnetic resonance imaging spinal abnormal	206/991 (20.8%)
Spinal X-ray abnormal	76/991 (7.7%)
C-reactive protein increased	40/991 (4%)
White blood cell count increased	12/991 (1.2%)
Blood triglycerides increased	10/991 (1%)
Metabolism and nutrition disorders
Hypertriglyceridaemia	14/991 (1.4%)
Musculoskeletal and connective tissue disorders
Back pain	158/991 (15.9%)
Pain in extremity	54/991 (5.4%)
Arthralgia	25/991 (2.5%)
Muscle spasms	17/991 (1.7%)
Nervous system disorders
Sciatica	27/991 (2.7%)
Headache	14/991 (1.4%)
Skin and subcutaneous tissue disorders
Rash	11/991 (1.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.