A Long-Term Safety and Efficacy Study of Lorecivivint in Subjects With Osteoarthritis of the Knee

A Long-Term Extension Study Evaluating the Safety and Efficacy of Lorecivivint in Subjects With Osteoarthritis of the Knee

Study OA-07 was a randomized, double-blind, placebo-controlled, Phase 3, multicenter, 2-year clinical trial that enrolled subjects from the recently completed Study OA-11 (NCT03928184).

The first 48 weeks of OA-07 the trial was placebo-controlled with subjects receiving the same randomized treatment received in OA-11. Investigators, research staff and subjects remained blinded to treatment allocation.

At Week 48, all subjects were administered LOR in the open-label portion of the trial.

At Visit 1E (on Day 1), upon completion of initial study procedures (e.g., informed consent, eligibility requirements, clinical evaluations including pregnancy testing [as applicable], baseline patient-reported outcome [PRO] assessments and safety data collection), subjects received a blinded IA injection of either LOR or PBO (as originally randomized in the parent [OA-11] study) into their target knee.

At Visit 3E (Week 48), upon completion of scheduled clinical, medical, safety and Patient-reported outcome (PRO) assessments, all subjects received an open-label injection of IA LOR into their target knee, such that previously PBO-treated subjects were effectively crossed over to the LOR treatment cohort.

Subjects were given the option to either receive a final injection of IA LOR into their target knee and complete both Visit 6E (Week 100) assessments and End-of-Study Visit assessments, or receive no injection and complete End-of-Study Visit assessments only. Subjects who had completed Visit 6E prior to the announcement of study closure were instructed to return to the clinic for End-of-Study Visit assessments.

Study OA-07's initial study design was to assess the safety and efficacy of additional treatment with LOR compared to PBO over one year and conclude at Visit 3E. The study was amended to become an open-label study at the Visit 3E that included an End-of-Study visit but without a specified time. The study was intended and described in the protocol to be run until such time as the Sponsor chose to close it. Study OA-07 was administratively closed at Visit 6E (Week 100), with no safety concerns, one year into the open-label study. For these reasons, Study OA-07 is considered a completed study.

Inclusion Criteria:

1. Completion of the Study SM04690-OA-11 (NCT03928184)
2. Compliance with procedures in study SM04690-OA-11, in the opinion of the Investigator
3. Fully understanding study requirements and willingness to comply with study visits and assessments
4. Understanding and signing of the informed consent form (ICF) prior to any study-related procedures

Exclusion Criteria:

1. 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
2. Any contraindications for an intra-articular (IA) injection in the target knee in the opinion of the Investigator
3. Any known reason identified by the Investigator or Sponsor that the subject may not be compliant with study visits or may no longer be an appropriate candidate for the study (e.g. planned major surgery, knee replacement during the parent study, planning to move away from the research site, or initiation of a prohibited concomitant medication including, but not limited to, IA injection of glucocorticoids, hyaluronic acid derivatives, platelet-rich plasma, stem cell therapies, or other agents with therapeutic intent into the target knee)
4. Participation in a clinical research trial (other than the prior SM04690-OA-11 study) that included the receipt of an investigational product (IP) or any experimental therapeutic procedure within 12 weeks before any study injection, or planned participation in any such trial
5. Current or pending disability claim, workers' compensation, or litigation(s) that may compromise response to treatment
6. Pregnant women, breastfeeding women, 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 Visit 1E (Day 1)
7. Women who are not post-menopausal or permanently surgically sterile who are sexually active, and who are not willing to use birth control (as outlined in the protocol) during the study period