Safety Study of PTP-001 for Treating Knee Osteoarthritis

Study Overview
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Brief Summary
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Evaluation of safety, tolerability, and efficacy of a single intra-articular (IA) injection of PTP-001, an allogeneic placental tissue particulate, in individuals with knee osteoarthritis (OA).

Detailed Description
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This open-label, dose-escalation study is expected to enroll 20 participants, 40-80 years of age and test two doses (low and high dose) of PTP-001, an allogeneic placental tissue particulate, in two unique cohorts of 10 participants each. Each participant will receive a single intra-articular (IA) injection of PTP-001. Following the completion of the first cohort in which 10 participants (Kellgren-Lawrence Grade 2 or 3 knee OA) will be treated with the low dose of PTP-001, safety data will be reviewed by an independent Data and Safety Monitoring Board (DSMB).

Official Title
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A Prospective, Open-Label, Dose-Escalation Phase 1 Study of Intra-Articular Administration of an Allogeneic Human Placental Tissue Particulate (PTP-001) for the Treatment of Knee Osteoarthritis

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Biological: Biological: PTP-001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written consent to participate in the study Male or female, aged 40 to 80 years Symptomatic knee OA with Kellgren-Lawrence radiographic classification of 2 or 3 Non-responsive after at least 3 months of conservative therapy for knee OA Females of childbearing potential must have negative pregnancy test result prior to treatment and must commit to highly effective methods of contraception for at least 6 months after treatment Willingness to report oral analgesic treatment used for knee pain and to discontinue analgesic treatment for knee pain in 24 hours prior to each study visit Willingness to limit use of pain rescue medication to oral acetaminophen for management of painful knee OA flare Exclusion Criteria: Body mass index (BMI) ≥ 40 kg/m2 or BMI ≥ 35 kg/m2 with condition that warrants weight loss surgery Presence of active infection of index knee or systemic infection requiring treatment within 3 months of Screening Administration of IA injection within 3 months of Screening Significant acute injury to index knee within 3 months of Screening Surgery to index knee within 6 months of Screening or planned surgery to index knee within 6 months after Screening Unstable index knee joint History of radiation therapy of index knee Known vascular or neurological disorder affecting the index knee Osteonecrosis of either knee Clinical diagnosis of inflammatory arthritis Clinical diagnosis of autoimmune disease affecting the musculoskeletal system Use of any other investigational therapy within 3 months of Screening or planned for the duration of the study Current anti-coagulant use History of receiving a solid organ or hematologic transplant History of malignancy or radiotherapy within 5 years of Screening, except for basal or squamous cell carcinoma of the skin Use of immunosuppressive or chemotherapeutic agents within 5 years of Screening Known allergy to local anesthetics or allograft tissues Known history of hepatitis Known history of thrombotic or thromboembolic phenomena. Known history of primary or secondary immunodeficiency disorders Presence of concurrent medical condition that, in the investigator's judgement, could compromise participant safety or interfere with the required study assessments and study participation. Note: Other protocol defined inclusion/exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Open-label, dose-escalation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PTP-001 - Low Dose (100 mg)<br>intra-articular injection of 100 mg PTP-001 resuspended with 4 mL of normal saline | Biological: Biological: PTP-001<br>* allogeneic placental tissue particulate<br>|
| Experimental: PTP-001 - High Dose (200 mg)<br>intra-articular injection of 200 mg PTP-001 resuspended with 4 mL of normal saline | Biological: Biological: PTP-001<br>* allogeneic placental tissue particulate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of local and systemic treatment emergent adverse events (AEs) and incidence of abnormal laboratory and immunogenicity panels | Incidence of local and systemic treatment emergent adverse events (AEs), including clinical laboratory and immunogenicity panels, after a single intra-articular injection of PTP-001. | Baseline to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Western Ontario and McMaster University (WOMAC) Pain Responder Rate |  | Week 26 and Week 52 | 
| WOMAC Physical Function Responder Rate |  | Week 26 and Week 52 | 
| Change from baseline in pain of the index knee, by evaluating the WOMAC Pain subscale score (the possible total score ranging from 0-50 for pain) | WOMAC Numerical Rating Scale (NRS) 3.1 questionnaire is a health status measure questionnaire of 24 questions comprising 3 subscales (pain, stiffness and physical function). WOMAC A (measure of pain) is measured on 11-point NRS ranging from 0 (none) to 10 (extreme), where higher score represents higher pain. | Baseline to Week 52 | 
| Change from baseline in physical function of the index knee, by evaluating the WOMAC Physical Function subscale score (the possible total score ranging from 0-170 for Physical Function) | WOMAC Numerical Rating Scale (NRS) 3.1 questionnaire is a health status measure questionnaire of 24 questions comprising 3 subscales (pain, stiffness and physical function). WOMAC C (measure of physical function) is measured on 11-point NRS ranging from 0 (none) to 10 (extreme), where higher score represents higher pain. | Baseline to Week 52 | 
| Change from baseline in patient global assessment of OA, by assessing the participants assessment of how they are doing considering arthritis in index knee (the possible answers include Very Good, Good, Acceptable, Poor, Very Poor |  | Baseline to Week 52 | 
| Change from baseline in health-related quality of life, by assessing the items from the Short Form 36 (SF-36) survey | The SF-36 measures 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health (the possible total normalized score ranges from 0-100). Higher scores on the SF-36 indicate better health status. | Baseline to Week 52 |