Overview

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

Status:
Completed
Trial end date:
2021-08-20
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Biosplice Therapeutics, Inc.
Samumed LLC
Treatments:
Adavivint
Lorecivivint
Criteria
Inclusion Criteria:

1. Males and females between 40 and 80 years of age, inclusive, in general good health
apart from their knee OA

2. Ambulatory (single assistive devices such as canes allowed if needed less than 50% of
the time, subjects requiring a walker are excluded)

3. 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)

4. 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

5. 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

6. Pain compatible with OA of the knee(s) for at least 26 weeks prior to the Screening
Visit

7. Primary source of pain throughout the body is due to OA in the target knee

8. Body mass index (BMI) ≤ 40 kg/m2 at the Screening Visit

9. Widespread Pain Index (WPI) score of ≤ 4 and a Symptom Severity Question 2 (SSQ2)
score of ≤ 2 at the Screening Visit and Day 1

10. Pain NRS scores recorded for the target knee on at least 4 out of the 7 days
immediately preceding Day 1

11. Pain NRS scores recorded for the nontarget knee on at least 4 out of the 7 days
immediately preceding Day 1

12. 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

13. 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

14. 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)

15. 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)

16. Willingness to use an electronic diary daily in the evening for the screening period
and 56-week study duration

17. 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

18. 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

19. Full understanding of the requirements of the study and willingness to comply with all
study visits and assessments

20. 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:

1. 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

2. 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

3. 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

4. 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

5. Partial or complete joint replacement in either knee

6. Currently requires use of a lower extremity prosthesis, and/or a structural knee brace
(i.e., a knee brace that contains hardware)

7. Any surgery (e.g., arthroscopy) in either knee within 26 weeks prior to Day 1

8. 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

9. Effusion of the target knee clinically requiring aspiration within 12 weeks prior to
Day 1

10. Use of electrotherapy, acupuncture, physical therapy, therapeutic ultrasound, and/or
chiropractic treatments for knee OA within 4 weeks prior to Day 1

11. Any bone fracture(s) within 26 weeks prior to the Screening Visit

12. Previous treatment with SM04690

13. Subjects who have previously failed screening on this protocol and fail to meet
rescreening criteria

14. 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

15. 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

16. Use of centrally acting analgesics within 12 weeks prior to Day 1

17. Use of anticonvulsants within 12 weeks prior to Day 1

18. Subjects requiring the use of opioids > 1x per week within 12 weeks prior to Day 1

19. 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

20. 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

21. 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

22. Clinically significant abnormal screening hematology values, blood chemistry values,
or urinalysis values as determined by the Investigator

23. 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

24. 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

25. 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

26. History of mania, bipolar disorder, psychotic disorder, schizophrenia, or
schizoaffective disorder

27. 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

28. 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.

29. Hemoglobin A1c (HbA1c) >9 at the Screening Visit

30. 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

31. Any contraindications for an IA injection in the target knee in the opinion of the
Investigator

32. Subjects who have a current or pending disability claim, workers' compensation, or
litigation(s) that may compromise response to treatment

33. 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

34. 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