STRIDES-X-ray: A Study Utilizing Patient-Reported and Radiographic Outcomes and Evaluating the Safety and Efficacy of Lorecivivint (SM04690) for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis

Sponsor

Biosplice Therapeutics, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT03928184

Collaborator

(none)

513

Enrollment

Locations

Arms

27.1

Actual Duration (Months)

5.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase 3 study is a multicenter, randomized, double-blind, placebo-controlled study of lorecivivint injected intra-articularly (IA) into the target knee (most painful) joint of moderately to severely symptomatic osteoarthritis (OA) subjects at a single dose of 0.07 mg lorecivivint per 2 mL injection. This study will utilize radiographs and patient reported outcomes (PROs) to evaluate the safety and efficacy of lorecivivint.

Condition or Disease	Intervention/Treatment	Phase
Knee Osteoarthritis	Drug: Lorecivivint Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

513 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 3, 56-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Utilizing Patient-Reported and Radiographic Outcomes to Evaluate the Efficacy and Safety of a Single Injection of SM04690 Injected in the Target Knee Joint of Moderately to Severely Symptomatic Osteoarthritis Subjects

Actual Study Start Date :

May 17, 2019

Actual Primary Completion Date :

Aug 20, 2021

Actual Study Completion Date :

Aug 20, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 0.07 mg lorecivivint One intra-articular injection of 0.07 mg lorecivivint in 2 ml vehicle	Drug: Lorecivivint Healthcare professional-administered intra-articular injection; performed on Day 1 Other Names: SM04690
Placebo Comparator: Vehicle One intra-articular injection of 0 mg lorecivivint in 2 ml vehicle	Drug: Placebo Healthcare professional-administered intra-articular injection; performed on Day 1

Arm

Intervention/Treatment

Experimental: 0.07 mg lorecivivint

One intra-articular injection of 0.07 mg lorecivivint in 2 ml vehicle

Drug: Lorecivivint

Healthcare professional-administered intra-articular injection; performed on Day 1

Other Names:

SM04690

Placebo Comparator: Vehicle

One intra-articular injection of 0 mg lorecivivint in 2 ml vehicle

Drug: Placebo

Healthcare professional-administered intra-articular injection; performed on Day 1

Outcome Measures

Primary Outcome Measures

Change from baseline in OA pain in the target knee (pain NRS) [Baseline and Week 12]
Evaluate change from baseline OA pain in the target knee as assessed by the weekly averages of daily pain numeric rating scale (NRS). The pain NRS is an 11-point scale [0-10] for subject self-reporting of average knee pain in the last 24 hours; 0 indicates no pain, and 10 represents the worst possible pain.

Secondary Outcome Measures

Change from baseline in OA pain in the target knee (Pain NRS) [Baseline, Weeks 24 and 52]
Evaluate change from baseline OA pain in the target knee as assessed by the weekly averages of daily pain Numeric Rating Scale (NRS). The pain NRS is an 11-point scale [0-10] for subject self-reporting of average knee pain in the last 24 hours; 0 indicates no pain, and 10 represents the worst possible pain.
Change from baseline in OA function in the target knee (WOMAC Function) [Baseline, Weeks 12, 24 and 52]
Evaluate change from baseline OA function in the target knee as assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function subscore (WOMAC Function). The WOMAC is a widely-used, proprietary outcome measurement tool used to evaluate the condition of subjects with OA of the knee and hip, including pain (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on a scale from 0 (lowest pain/lowest stiffness/highest function) to 4 (highest pain/highest stiffness/lowest function). The WOMAC Function subscore ranges from 0 to 68.
Change from baseline in OA disease activity (Patient Global Assessment) [Baseline, Weeks 12, 24 and 52]
Evaluate change from baseline OA disease activity as assessed by Patient Global Assessment. The Patient Global Assessment is an 11-point [0-10] Numeric Rating Scale [NRS] on which the subjects will rate how they feel their target knee OA is doing, considering all the ways in which their target knee OA may affect them. The NRS is anchored by descriptors at each end ("Very Good" on the left and "Very Bad" on the right).
Change from baseline in usage of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen for target knee OA pain [Baseline and Week 52]

Other Outcome Measures

Change from baseline in serum bone biomarkers [Baseline and Week 56]
Evaluate change from baseline in serum bone biomarkers N-terminal propeptides of procollagen type I [PINP] and β-C-terminal telopeptide [β-CTX]
Change from baseline in a serum cartilage biomarker [Baseline and Week 56]
Evaluate change from baseline in serum cartilage biomarker cartilage oligomeric matrix protein [COMP]
Change from baseline in medial joint space width (mJSW) in the target knee [Baseline and Week 52]
Evaluate change from baseline in mJSW as documented by radiograph of the target knee
Change from baseline in health-related quality of life (HRQOL) [Baseline and Week 52]
Evaluate change from baseline in HRQOL as assessed by the 36-Item Short Form Health Survey (SF-36). The SF-36 consists of eight scaled scores which are the weighted sums of the questions in their section (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health). Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. A score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Change from baseline in OA pain in the target knee (WOMAC Pain) [Baseline, Weeks 12, 24 and 52]
Evaluate change from baseline in OA pain in the target knee as assessed by WOMAC pain subscore (WOMAC Pain). The WOMAC is a widely-used, proprietary outcome measurement tool used to evaluate the condition of subjects with OA of the knee and hip, including pain (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on a scale from 0 (lowest pain/lowest stiffness/highest function) to 4 (highest pain/highest stiffness/lowest function). The WOMAC Pain subscore ranges from 0 to 20.
Change from baseline in OA pain, function and stiffness (WOMAC Total score) [Baseline, Weeks 12, 24 and 52]
Evaluate change from baseline in OA pain, function and stiffness as a composite outcome measure as assessed by WOMAC Total score. The WOMAC is a widely-used, proprietary outcome measurement tool used to evaluate the condition of subjects with OA of the knee and hip, including pain (5 questions), stiffness (2 questions), and physical functioning (17 questions) of the joints. Each question is measured on a scale from 0 (lowest pain/lowest stiffness/highest function) to 4 (highest pain/highest stiffness/lowest function). WOMAC Total is a composite of the three domains (pain/stiffness/function) with a total score of 0 to 96.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Males and females between 40 and 80 years of age, inclusive, in general good health apart from their knee OA
Ambulatory (single assistive devices such as canes allowed if needed less than 50% of the time, subjects requiring a walker are excluded)
Diagnosis of femorotibial OA in the target knee by standard American College of Rheumatology (ACR) criteria at the Screening Visit (clinical AND radiographic criteria); OA of the knee is not to be secondary to any rheumatologic conditions (e.g., rheumatoid arthritis)
mJSW by radiograph between 1.5 and 4 mm, inclusive, in the target knee within 12 weeks of the Screening Visit as assessed by independent central readers
Radiographic disease Stage 2 or 3 in the target knee within 12 weeks of the Screening Visit according to the Kellgren-Lawrence (KL) grading of knee OA as assessed by independent central readers
Pain compatible with OA of the knee(s) for at least 26 weeks prior to the Screening Visit
Primary source of pain throughout the body is due to OA in the target knee
Body mass index (BMI) ≤ 40 kg/m2 at the Screening Visit
Widespread Pain Index (WPI) score of ≤ 4 and a Symptom Severity Question 2 (SSQ2) score of ≤ 2 at the Screening Visit and Day 1
Pain NRS scores recorded for the target knee on at least 4 out of the 7 days immediately preceding Day 1
Pain NRS scores recorded for the nontarget knee on at least 4 out of the 7 days immediately preceding Day 1
Daily OA knee pain diary average NRS intensity score ≥ 4 and ≤ 8 in the target knee on the 11-point (0-10) NRS scale for the 7 days immediately preceding Day 1
Daily OA knee pain diary average NRS intensity score < 4 in the nontarget knee on the 11-point (0-10) NRS scale for the 7 days immediately preceding Day 1
WOMAC Pain of 20-40 (out of 50) for the target knee at baseline regardless of if the subject is on symptomatic oral treatment (baseline questionnaire completed during the screening period prior to randomization)
WOMAC Function of 68-136 (out of 170) for the target knee at baseline regardless of if the subject is on symptomatic oral treatment (baseline questionnaire completed during the screening period prior to randomization)
Willingness to use an electronic diary daily in the evening for the screening period and 56-week study duration
Negative drug test for amphetamine, buprenorphine, cocaine, methadone, opiates, phencyclidine (PCP), propoxyphene, barbiturates, benzodiazepine, methaqualone, and tricyclic antidepressants, unless any of these drugs are allowed per protocol and prescribed by a physician to treat a specific condition
Subjects with depression or anxiety must be clinically stable for at least 12 weeks prior to the Screening Visit and, if on treatment for depression or anxiety, be on at least 12 weeks of stable therapy
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 (ICF), and must have signed and dated it prior to any study-related procedure being performed

Exclusion Criteria:

Pregnant women, breastfeeding woman, and women who are not post-menopausal (defined as 12 months with no menses without an alternative medical cause) or permanently surgically sterile (includes hysterectomy, bilateral salpingectomy, and bilateral oophorectomy), who have a positive or indeterminate pregnancy test result at the Screening Visit or Day 1
Women who are not post-menopausal or permanently surgically sterile who are sexually active, and who are not willing to use birth control during the study period
Men who are sexually active and of reproductive potential, who have partners who are capable of becoming pregnant, and who are not willing to use birth control during the study period
Significant malalignment of anatomical axis (medial angle formed by the femur and tibia) of the target knee (varus > 10°, valgus > 10°) by radiograph within 12 weeks of the Screening Visit as assessed by independent central readers
Partial or complete joint replacement in either knee
Currently requires use of a lower extremity prosthesis, and/or a structural knee brace (i.e., a knee brace that contains hardware)
Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to Day 1
Intra-articular (IA) injection into the target knee with a therapeutic aim including, but not limited to, hyaluronic acid, platelet-rich plasma (PRP),and stem cell therapies within 26 weeks prior to Day 1, or IA glucocorticoids within 12 weeks prior to Day 1
Effusion of the target knee clinically requiring aspiration within 12 weeks prior to Day 1
Use of electrotherapy, acupuncture, physical therapy, therapeutic ultrasound, and/or chiropractic treatments for knee OA within 4 weeks prior to Day 1
Any bone fracture(s) within 26 weeks prior to the Screening Visit
Previous treatment with SM04690
Subjects who have previously failed screening on this protocol and fail to meet rescreening criteria
Participation in a clinical research trial that included the receipt of an investigational product (IP) or any experimental therapeutic procedure within 26 weeks prior to the Screening Visit, or planned participation in any such trial
Treatment with systemic (oral, intramuscular, or intravenous) glucocorticoids ≥10 mg prednisone or the equivalent per day within 4 weeks prior to Day 1, or subjects on <10 mg prednisone or the equivalent per day who have not maintained a stable regimen for at least 2 weeks prior to Day 1 in the opinion of the Investigator
Use of centrally acting analgesics within 12 weeks prior to Day 1
Use of anticonvulsants within 12 weeks prior to Day 1
Subjects requiring the use of opioids > 1x per week within 12 weeks prior to Day 1
Topical local anesthetic agents (gels, creams, or patches such as the Lidoderm patch) used for the treatment of knee OA within 7 days of Day 1
Planned surgery scheduled during the study period, not including non-surgical invasive procedures conducted for a diagnostic or therapeutic purpose scheduled during the study period
History of malignancy within the last 5 years, not including subjects with prior history of adequately treated in situ cervical cancer or basal or squamous cell skin cancer
Clinically significant abnormal screening hematology values, blood chemistry values, or urinalysis values as determined by the Investigator
Any condition, that, in the opinion of the Investigator, constitutes a risk or contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation
Other conditions that, in the opinion of the Investigator, could affect study endpoint assessments of either knee, including, but not limited to, peripheral neuropathy (e.g., diabetic neuropathy), symptomatic hip osteoarthritis, symptomatic degenerative disc disease, and patellofemoral syndrome
Comorbid conditions that could affect study endpoint assessments of the target knee, including, but not limited to, rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, gout or pseudogout, and fibromyalgia
History of mania, bipolar disorder, psychotic disorder, schizophrenia, or schizoaffective disorder
Any known active infections, including urinary tract infection, upper respiratory tract infection, sinusitis, suspicion of IA infection, hepatitis B or hepatitis C infection, and/or infections that may compromise the immune system such as human immunodeficiency virus (HIV) at Day 1
Any chronic condition that has not been well controlled or subjects with a chronic condition who have not maintained a stable therapeutic regimen of a prescription therapy in the opinion of the Investigator.
Hemoglobin A1c (HbA1c) >9 at the Screening Visit
If using NSAIDs and/or acetaminophen, subjects who have not maintained a stable regimen in the opinion of the Investigator for at least 4 weeks prior to Day 1
Any contraindications for an IA injection in the target knee in the opinion of the Investigator
Subjects who have a current or pending disability claim, workers' compensation, or litigation(s) that may compromise response to treatment
Subjects who are immediate family members (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study at any investigative site, or are directly affiliated with the study at any investigative site
Subjects employed by Samumed, LLC, or any of its affiliates or development partners (that is, an employee, temporary contract worker, or designee) responsible for the conduct of the study, or who are immediate family members (spouse, parent, child, or sibling; biological or legally adopted) of said employees responsible for the conduct of the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35205
2	Research Site	Birmingham	Alabama	United States	35215
3	Research Site	Birmingham	Alabama	United States	35216
4	Research Site	Peoria	Arizona	United States	85381
5	Research Site	Phoenix	Arizona	United States	85037
6	Research Site	Tucson	Arizona	United States	85712
7	Research Site	Little Rock	Arkansas	United States	72205
8	Research Site	Anaheim	California	United States	92805
9	Research Site	Garden Grove	California	United States	92840
10	Research Site	Norco	California	United States	92860
11	Research Site	Pomona	California	United States	91767
12	Research Site	San Diego	California	United States	92103
13	Research Site	San Marcos	California	United States	92078
14	Research Site	Spring Valley	California	United States	91978
15	Research Site	Westminster	California	United States	92683
16	Research Site	Boulder	Colorado	United States	80301
17	Research Site	Colorado Springs	Colorado	United States	80918
18	Research Site	Denver	Colorado	United States	80209
19	Research Site	Waterbury	Connecticut	United States	06708
20	Research Site	Clearwater	Florida	United States	33761
21	Research Site	Coral Gables	Florida	United States	33134
22	Research Site	Hialeah	Florida	United States	33016
23	Research Site	Miami Lakes	Florida	United States	33014
24	Research Site	Miami	Florida	United States	33143
25	Research Site	Orlando	Florida	United States	32806
26	Research Site	Oviedo	Florida	United States	32765
27	Research Site	Port Orange	Florida	United States	32127
28	Research Site	Sunrise	Florida	United States	33351
29	Research Site	West Palm Beach	Florida	United States	33409
30	Research Site	Winter Haven	Florida	United States	33880
31	Research Site #1	Winter Park	Florida	United States	32789
32	Research Site #2	Winter Park	Florida	United States	32789
33	Research Site	Marietta	Georgia	United States	30060
34	Research Site	Newnan	Georgia	United States	30265
35	Research Site	Stockbridge	Georgia	United States	30281
36	Research Site	Woodstock	Georgia	United States	30189
37	Research Site	Boise	Idaho	United States	83713
38	Research Site	Meridian	Idaho	United States	83642
39	Research Site	Bloomington	Illinois	United States	61704
40	Research Site	Gurnee	Illinois	United States	60031
41	Research Site	Oak Brook	Illinois	United States	60523
42	Research Site	Rockford	Illinois	United States	61114
43	Research Site	Anderson	Indiana	United States	46011
44	Research Site	Evansville	Indiana	United States	47714
45	Research Site	Valparaiso	Indiana	United States	46383
46	Research Site	Kansas City	Kansas	United States	66160
47	Research Site	Wichita	Kansas	United States	67205
48	Research Site	Monroe	Louisiana	United States	71203
49	Research Site	New Orleans	Louisiana	United States	70124
50	Research Site	Wheaton	Maryland	United States	20902
51	Research Site	Boston	Massachusetts	United States	02111
52	Research Site	Bay City	Michigan	United States	48706
53	Research Site	Troy	Michigan	United States	48085
54	Research Site	Hazelwood	Missouri	United States	63042
55	Research Site	Saint Louis	Missouri	United States	63141
56	Research Site	La Vista	Nebraska	United States	68128
57	Research Site	Lincoln	Nebraska	United States	68516
58	Research Site	Omaha	Nebraska	United States	68114
59	Research Site	Albuquerque	New Mexico	United States	87108
60	Research Site	Great Neck	New York	United States	11021
61	Research Site	Hartsdale	New York	United States	10530
62	Research Site	New York	New York	United States	10016
63	Research Site 1	New York	New York	United States	10021
64	Research Site 2	New York	New York	United States	10021
65	Research Site	Rochester	New York	United States	14609
66	Research Site	Williamsville	New York	United States	14221
67	Research Site	Charlotte	North Carolina	United States	28209
68	Research Site	Leland	North Carolina	United States	28451
69	Research Site	Salisbury	North Carolina	United States	28144
70	Research Site	Winston-Salem	North Carolina	United States	27103
71	Research Site	Fargo	North Dakota	United States	58104
72	Research Site	Cincinnati	Ohio	United States	45219
73	Research Site	Cincinnati	Ohio	United States	45224
74	Research Site	Cincinnati	Ohio	United States	45242
75	Research Site	Columbus	Ohio	United States	43235
76	Research Site	Oklahoma City	Oklahoma	United States	73103
77	Research Site	Oklahoma City	Oklahoma	United States	73112
78	Research Site	Duncansville	Pennsylvania	United States	16635
79	Research Site	Fort Mill	South Carolina	United States	29707
80	Research Site	Greenville	South Carolina	United States	29607
81	Research Site	Greer	South Carolina	United States	29651
82	Research Site	Mount Pleasant	South Carolina	United States	29464
83	Research Site	Rapid City	South Dakota	United States	57702
84	Research Site	Austin	Texas	United States	78745
85	Research Site	Bedford	Texas	United States	76021
86	Research Site	Carrollton	Texas	United States	75007
87	Research Site	Dallas	Texas	United States	75231
88	Research Site	Edinburg	Texas	United States	78539
89	Research Site	Houston	Texas	United States	77029
90	Research Site	Houston	Texas	United States	77055
91	Research Site	Plano	Texas	United States	75075
92	Research Site	San Antonio	Texas	United States	78215
93	Research Site	San Antonio	Texas	United States	78229
94	Research Site	San Antonio	Texas	United States	78258
95	Research Site	Draper	Utah	United States	84020
96	Research Site	Murray	Utah	United States	84123
97	Research Site	Salt Lake City	Utah	United States	84107
98	Research Site	Charlottesville	Virginia	United States	22911
99	Research Site	Richmond	Virginia	United States	23219