Study of OLP-1002 Injections for Reducing Moderate to Severe Pain Due to Osteoarthritis in Hip and/or Knee Joint

The study consists of two Stages (Stage 1 and Stage 2)

Stage 1: It is an open-label, dose-finding study employing a single ascending dose design to determine appropriate dose level starting dose of OLP-1002 for Stage 2 of the study in participants with moderate to severe pain due to osteoarthritis in a hip and/or knee joint.

Stage 1 consists of following:

• Screening period: up to 15 days (± 2 days) (defined as Day -23 to -9)
• Washout period: 5 days (± 1 day) (defined as Day -8 to -4)
• Baseline period: 3 days (± 1 day) (defined as Day -3 to -1)
• Treatment period: 1 day (defined as Day 1): participants will be subcutaneously administered a single dose of OLP-1002 at the assigned dose level (1 μg, 3 μg, 10 μg, 25 μg, 50 μg, 80 μg)
• Follow-up period: 30 days (± 5 days) (defined as Day 2 to 30)

Approximately 30 participants will be enrolled in Stage 1 of the study

Stage 2: The study will be a double-blind, placebo-controlled, parallel-arm study of up to 2 selected single doses of OLP-1002 to evaluate the efficacy of OLP-1002 in the treatment of pain in participants with moderate to severe pain due to osteoarthritis in a knee or hip joint.

Dose levels for Stage 2 will be 1 μg and 2 μg of OLP-1002. Dose selection was based on the conclusions drawn from the internal efficacy data review analysis conducted by Sponsor from data collected in Stage 1 of the study.

Stage 2 consists of following:

• Screening Period: up to 14 days (± 2 days)
• Baseline Period: 3 days (± 1 day)
• Treatment: 1 day (± 2 days)
• Follow-up period: 42 days from last dose, D43 (± 5 days)

Approximately 90 participants will be enrolled in Stage 2 of the study

Inclusion criteria

• Willing and able to provide written informed consent prior to any study-related procedures being performed in accordance with Good Clinical Practice (GCP), International Council for Harmonisation (ICH) and local regulations.
• Male or female aged ≥ 35 years to ≤ 70 years as of the date of enrolment into the study
• No history of cardiac disease including arterial or venous thrombi, cardiac arrhythmia, myocardial infarction, admission to hospital for unstable angina, cardiac angioplasty or stent implantation within 90 days prior to Screening.
• Body mass index (BMI) ≥ 18 kg/m2 < 40 kg/m2 at Screening.
• Pain in hip or knee joints, every day for at least 1-month during the 3 months prior to Screening.

Note: Participants must have a pain severity score of ≥ 5 based on the 3-day mean VAS score during the Baseline Period and must have recorded the pain score every day during the Baseline Period.

• Diagnosis of Osteoarthritis (OA) of the index hip or knee: moderate to severe osteoarthritis, based on American College of Rheumatology (ACR) criteria with Kellgren Lawrence x-ray grade of at least 2, as diagnosed by the radiologist or rheumatologist.
• Western Ontario and McMaster Universities Osteoarthritis (WOMAC) pain score of ≥ 10 out of 20 in the index hip or knee at Screening.
• Willing and able to provide their historical use of nonsteroidal anti-inflammatory drugs (NSAIDs) either over-the-counter (OTC) per recommendation of a physician or prescribed during the past 6 months (the pain in the target knee and/or hip required).
• Women of childbearing potential (WOCBP) must be non-pregnant and non-lactating, and must use acceptable, highly effective double contraception from Screening until 90 days after the last dose of IP. Double contraception is defined as a condom AND one other form of the following:

• Established hormonal contraception (for example, approved oral contraceptive pills [OCPs], long-acting implantable hormones, injectable hormones),
• A vaginal ring or an intrauterine device (IUD), or
• Documented evidence of surgical sterilisation at least 6 months prior to Screening (eg, tubal occlusion, hysterectomy, bilateral salpingectomy, or bilateral oophorectomy for women or vasectomy for men [with appropriate post-vasectomy documentation of the absence of sperm in semen] provided the male partner is a sole partner).

Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not considered highly effective methods of birth control. A participant's treatment is acceptable.

• Women not of childbearing potential must be postmenopausal for ≥ 12 months. Post-menopausal status will be confirmed through testing of FSH levels ≥ 40 IU/L at Screening for amenorrhoeic female participants. Female participants who are abstinent from heterosexual intercourse will also be eligible.

Female participants who are in a same-sex relationship are not required to use contraception.

• Male participants must be surgically sterile (>30 days since vasectomy with no viable sperm), abstinent, or if engaged in sexual relations with a WOCBP, the participant and his partner must be surgically sterile (eg, tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or using an acceptable, highly effective contraceptive method from Screening until 90 days after the last dose of IP. Acceptable methods of contraception include the use of condoms and the use of an effective contraceptive for the female partner that includes: OCPs, long-acting implantable hormones, injectable hormones, a vaginal ring or an IUD.

Male participants with a same-sex partner (abstinence from penile-vaginal intercourse) are eligible when this is their preferred and usual lifestyle.

• WOCBP must have a negative pregnancy test at Screening and Day 1 and be willing to have additional pregnancy tests as required throughout the study.
• Male participants must agree not donate sperm for at least 90 days after the last dose of IP.
• Agree to maintain their usual levels of activity throughout the course of the study.
• Willing to abstain from other intra-articular treatments of the joint and any joint surgery while on the study.
• Able to comply with study procedures, including the completion of daily questionnaires.
• Subjects suffering from moderate to severe pain secondary to diagnosed OA of the knee and/or hip joint with fit for range of age & BMI will be included with proof of COVID 19 full vaccinations and intention of the participation in the study.

Exclusion criteria

• Known history or current symptomatic heart failure as per New York Heart Association (NYHA) classes II-IV, including unstable angina, myocardial infarction, serious cardiac arrhythmia, cerebral vascular accident, coronary/peripheral artery bypass graft surgery, transient ischaemic attack, or pulmonary embolism within 90 days prior to Screening.

Participants with small pulmonary embolism not thought to put participants at higher risks of AEs may be allowed on a case-by-case basis in discussion with Sponsor.

• History of malignancy except for basal cell carcinoma with successful removal, ALL other non-melanoma skin cancers excised successfully more than 2 years ago, and cervical intraepithelial neoplasia that has been successfully cured more than 5 years prior to the Screening Period.
• Any of the following:

• Intra-articular treatment injections (including but not limited to corticosteroids, hyaluronic acid, platelet rich plasma, BOTOX®, local anaesthetics) within 3 months prior to the Screening period,
• QTcF > 450 ms confirmed by repeat ECG measurement,
• QRS duration > 120 ms confirmed by repeat ECG measurement,
• PR interval > 220 ms confirmed by repeat ECG measurement,
• Findings which would make QTc measurements difficult or QTcF data uninterpretable as per Investigator discretion,
• History of additional risk factors for torsades de pointes (eg, heart failure (class III/IV according to the New York Heart Association [NYHA]), hypo/hyperkalaemia, family history of long QT syndrome), or
• Taking any arrhythmic or arrythmia evoking agents.
• Unable or unwilling to cease the use of all pain reducing medications and all pain reducing devices, prescription or otherwise, as of the first day of the study Baseline Period and until the End of Study visit. These include all topical and oral opioid and antiinflammatory medications, herbal and homeopathic remedies, electrostimulation therapy (EST) and neuromuscular re-education (NMRE). This excludes the use of paracetamol provided that a participant is able and willing to utilise paracetamol/acetaminophen (2 g/day) as rescue medication or up to 4 g/day for intolerable pain following consent from the PI (or designee) without prior approval from the Sponsor, as of the first day of the study, Baseline Period, and until the End of Study visit.

Note: The participant may continue taking usual medication for maintenance of health.

• Any of the following laboratory abnormalities within 14 days of Day 1:

• Platelet count < 100,000 cells/mm3.
• Total neutrophil count < 1500 cells/mm3.
• Serum creatinine ≥ 1.5 x upper limit of normal (ULN).
• Alanine aminotransferase (ALT) > 3.0 x ULN).
• Aspartate aminotransferase (AST) > 3.0 x ULN.
• Alkaline phosphatase > 2.0 x ULN.
• Bilirubin > 1.5 x ULN.
• Aural Temperature ≥ 38 degree Celsius or other evidence of an infection.
• History of alcoholism, substance abuse or dependence during the 12 months prior to Screening:

• During the study, alcohol consumption of > 21 units per week for males and > 14 units per week for females will not be allowed. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits.
• Positive urine drug screen (confirmed by repeat) or alcohol consumption (self-report) higher than the permissible limit, as mentioned above, at Screening or Baseline shall be excluded from the study.
• Has an allergy or hypersensitivity to OLP-1002 or its constituents.
• Female participants who are pregnant at Screening or are planning on becoming pregnant, or are currently breastfeeding up to 90 days from end of study.
• Any medical condition or comorbidities as assessed by the Investigator, that could adversely impact study participation or safety, conduct of the study, or interfere with pain assessments.
• Active skin conditions such as dermatitis, allergy, eczema, psoriasis, or abnormal skin healing. This criterion is applied in general and is not limited to the active disease at the planed injection site.
• Tattoos, scars, or moles that in the opinion of the Investigator are likely to interfere with dosing or study assessments at any of the potential injection sites.
• Depression of moderate or greater severity as assessed by the Investigator or via the Patient Health Questionnaire (PHQ-9 ≥10) at the Screening visit.
• History of psychotic symptoms, whether controlled or not and/or requiring antipsychotic treatment, or history of a suicidal attempt/s within 180 days prior to Screening.
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndromerelated illness, acute or history of chronic hepatitis B or C. Positive tests for HIV-1 or HIV-2 antibodies, hepatitis B surface antigen, or hepatitis C antibodies at Screening.
• Concurrent medical or arthritic conditions that could interfere with evaluation of the index joint including fibromyalgia, rheumatoid arthritis, or other inflammatory arthropathies affecting the joint eg, sciatica, diabetic neuropathy, multiple sclerosis.
• Has undergone arthroscopic or open surgery to the joint within 180 days of Screening visit.
• Has undergone replacement surgery of the treatment joint within 180 days of Screening visit.
• The presence of surgical hardware /medical device or other foreign bodies in the treatment joint within 180 days of Screening visit.
• Use or intend to use any prescription medications/products other than those medications for health conditions (eg, hypertension, diabetes or other disease), within 14 days prior to the Screening visit until the EOS (End of Study) Visit, unless deemed acceptable by the Investigator (or designee).

Note: Prescription medication is permitted except for pain control, if deemed acceptable by the Investigator (or designee).

• Use or intend to use slow-release medications/products considered to still be active within 14 days prior to the Screening visit until the EOS Visit, unless deemed acceptable by the Investigator (or designee).
• Receipt of blood products within 60 days prior to the Screening visit until the EOS Visit.
• Donation of blood from 90 days prior to Screening until the EOS Visit, plasma from 14 days prior to Screening until the EOS Visit, or platelets from 42 days prior to Screening until the EOS Visit.
• Poor peripheral venous access.
• Is a Sponsor employee.
• Has participated in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days or 5 half-lives of the IP, whichever is longer, prior to the Screening visit.
• Has participated in any trial of a device, supplement, cognitive/behavioural therapy, physiotherapy or active exercise study within 30 days prior to the Screening visit.
• Has previously received any dose of OLP-1002.
• In the opinion of the Investigator (or designee), should not participate in this study.
• Subjects who have history of or current serious illness with cardiac, vascular, cancer, infectious, mental, and laboratory abnormality will be excluded from this study.