A Phase 1/2a Study to Evaluate Single Intraarticular Injections of 3 Dose Levels of SYN321 and Placebo in Patients With Symptomatic Knee Osteoarthritis

NCT06989645 | Completed Phase 1

• 2 other identifiers: SYN321-012024-517920-21-00
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This is a, phase 1/2a trial, to assess the safety, tolerability, systemic exposure as well as preliminary efficacy following a single intra-articular injection of 3 dose levels of SYN321 in patients with symptomatic knee osteoarthritis (KOA).

Conditions

Osteoarthritis of Knee

Keywords

knee osteoarthritis

Outcome Measures

Primary Outcomes (9)

• Incidence and intensity of adverse events

  Frequency, intensity and seriousness of adverse events (AEs) will be assesed. The intensity grades is defined as mild, moderate or severe. AEs will be assessed as not related, possibly or probably related to SYN321

  From IMP injection (day 1) until end of trial visit (day 56)

• Clinically significant changes in ECG

  Single 12-lead ECGs will be recorded in supine position after 10 minutes of rest using an ECG machine. The resting heart rate and PQ/PR, QRS, QT and QTcF intervals will be recorded. Any values outside of normal ranges will be judged as clinically significant or not clinically significant by the Investigator. Abnormal post-IMP administration findings assessed by the Investigator as clinically significant will be reported as Adverse Events.

  From screening until end of trial visit (day 56)

• Clinically significant changes in blood pressure

  Systolic and diastolic blood pressure and pulse will be measured in supine positionafter 10 minutes of rest. Any vital signs outside of normal ranges will be judged as clinically significant or not clinically significant by the Investigator. Abnormal post-IMP administration findings assessed by the Investigator as clinically significant will be reported as Adverse Events.

  From screening until end of trial visit (day 56)

• Clinically significant changes in heart rate

  Heart rate will be measured in supine position after 10 minutes of rest. Any vital signs outside of normal ranges will be judged as clinically significant or not clinically significant by the Investigator. Abnormal post-IMP administration findings assessed by the Investigator as clinically significant will be reported as Adverse Events.

  From screening until end of trial visit (day 56)

• Clinically significant changes in body temperature

  Body temperature will be measured in supine position after 10 minutes of rest. Any vital signs outside of normal ranges will be judged as clinically significant or not clinically significant by the Investigator. Abnormal post-IMP administration findings assessed by the Investigator as clinically significant will be reported as Adverse Events.

  From screening until end of trial visit (day 56)

• Clinically significant changes in Clinical Laboratory Profile

  Safety laboratory data, Clinical chemistry, haematology, and coagulation, will be measured. Any values outside of normal ranges will be judged as clinically significant or not clinically significant by the Investigator. Abnormal post-IMP administration findings assessed by the Investigator as clinically significant will be reported as Adverse Events.

  From screening until end of trial visit (day 56)

• Clinically significant changes in urine analysis

  Urine analysis will be performed. Any values outside of normal ranges will be judged as clinically significant or not clinically significant by the Investigator. Abnormal post-IMP administration findings assessed by the Investigator as clinically significant will be reported as Adverse Events.

  From screening until end of trial visit (day 56)

• Clinically significant changes in Physical Examination

  Assessment of different organ systems. Any abnormalities will be specified and documented as clinically significant or not clinically significant. Abnormal post-IMP administration findings assessed by the Investigator as clinically significant will be reported as AEs

  From screening until end of trial visit (day 56)

• Clinically significant changes of local tolerability reactions

  The infusion site area will be visually inspected at baseline and follow up-visits after the IMP injection. The assessment will include the Investigator's evaluation of swelling, Redness and warmth. Abnormal post-IMP administration findings assessed by the Investigator as clinically significant will be reported as AEs.

  From screening until end of trial visit (day 56)

Secondary Outcomes (10)

• Pharmacokinetic (PK) parameter in plasma - Cmax

  From IMP injection (day 1) until end of trial visit (day 56)

• Pharmacokinetic (PK) parameter in plasma - Cmax

  From IMP injection (day 1) until end of trial visit (day 56)

• Pharmacokinetic (PK) parameter in urine - Cmax

  From IMP injection (day 1) until end of trial visit (day 56)

• Pharmacokinetic (PK) parameter in urine - Cmax

  From IMP injection (day 1) until end of trial visit (day 56)

• Pharmacokinetic (PK) parameter in plasma - AUC

  From IMP injection (day 1) until end of trial visit (day 56)

Study Arms (5)

SYN321, dose level 1

ACTIVE COMPARATOR

Cohort 1: 6 participants recieves SYN321.

Drug: SYN321

SYN321, dose level 2

ACTIVE COMPARATOR

Cohort 2: 6 participants recieves SYN321.

Drug: SYN321

SYN321, dose level 3

ACTIVE COMPARATOR

Cohort 3: 6 participants recieves SYN321.

Drug: SYN321

SYN321, dose level 1,2 or 3

ACTIVE COMPARATOR

Cohort 4: 6 participants recieves SYN321.

Drug: SYN321

Placebo

PLACEBO COMPARATOR

Placebo: 2 participants each from cohort 1, 2 and 3, and 6 participants from cohort 4 receive placebo.

Drug: Placebo

Interventions

SYN321 DRUG

Intra-articular

SYN321, dose level 1; SYN321, dose level 1,2 or 3; SYN321, dose level 2; SYN321, dose level 3

Placebo DRUG

Intra-articular

Also known as: NaCl 9 mg/mL

Placebo

Eligibility Criteria

• Age: 40 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to give electronically informed consent for participation in the trial and willing and able to participate in all procedures and follow-up evaluations necessary to complete the trial.
• Male or female patient clinically diagnosed with KOA, no later than 3 months prior to Visit 1. The KOA diagnosis should be confirmed in the patient's medical record.
• Age 40 to 79 years, inclusive at the time of Visit 1.
• Body mass index (BMI) ≥ 18.5 and \< 35.0 kg/m2.
• Patients without abnormal clinically significant medical history, physical findings, vital signs, hypotension, cardiovascular disease, ECG, and laboratory values at the time of the screening visit, as judged by the Investigator. (Discussion is encouraged between the Investigator and the Medical Monitor regarding the clinical relevance of any abnormal laboratory value during the pre-dose period.)
• Patient is willing to discontinue all pain medication (COX-2 inhibitors, NSAIDs, and opioid analgesics) at least 10 days before trial drug administration (prior to Day 1) and for the trial duration. Paracetamol will be allowed as rescue medication up to max 4000 mg/day (except for 24 hours prior to visit to the trial site).
• Patient agrees not to take additional knee symptom-modifying drugs (e.g., glucosamine, collagen, HA) at least 10 days before trial drug administration (prior to Day 1) and for the trial duration.
• WOCBP must practice abstinence heterosexual intercourse (only allowed when this is the preferred and usual lifestyle of the patient) or agree to use a highly effective method of contraception with a failure rate of \< 1 % to prevent pregnancy from that least 2 weeks prior to the administration of IMP to 4 weeks after the last administration of IMP. In addition, any male partner of a female patient must, unless he has undergone vasectomy, agree to use a condom from the first administration of IMP until 4 weeks after the last administration of IMP.
• The following are considered highly effective methods of contraception:
• combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal),
• progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable),
• intrauterine device \[IUD\]or intrauterine hormone-releasing system \[IUS\]). WOCBP must refrain from donating eggs from the first IMP administration until 3 months after the last IMP administration.
• Women of non-childbearing potential are pre-menopausal females who have undergone any of the following surgical procedures; hysterectomy, bilateral salpingectomy, or bilateral oophorectomy, or who are post-menopausal defined as 12 months of amenorrhea (in questionable cases a blood sample with detection of follicle stimulating hormone \[FSH\] \>25 IU/L is confirmatory).
• Male patients must be willing to use condom or be vasectomized or practice sexual abstinence from heterosexual intercourse (only allowed when this is the preferred and usual lifestyle of the patient) to prevent pregnancy and drug exposure of a partner and refrain from donating sperm from the first administration of IMP until 3 months after the last administration of IMP. Any female partner of a non-vasectomized male patient who is of childbearing potential must use contraceptive methods with a failure rate of \< 1% to prevent pregnancy (see above) from at least 2 weeks prior to the first administration of IMP to 4 weeks after the last administration of IMP.
• Patients without contraindications for treatment with diclofenac.

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the trial, or influence the results or the patient's ability to participate in the trial.
• Previous IA fracture of the knee.
• Patient has rheumatoid arthritis, psoriatic arthritis, or has been diagnosed with any other disorders that is the primary source of their knee pain, including but not limited to: osteonecrosis, radiculopathy, bursitis, tendinitis, tumor, cancer.
• IA injections of steroids or HA or other invasive procedure (e.g., arthroscopy, arthrography, surgery) in the knee within 3 months prior to screening.
• Conditions or medications that could confound the assessment of pain, as judged by the Investigator.
• Conditions that could be adversely affected by an IA injection (e.g., eczema, skin infection, high bleeding risk etc.), as judged by the Investigator.
• Any clinically significant illness (except KOA), medical/surgical procedure, or trauma within 4 weeks of the administration of IMP.
• Malignancy within the past 5 years, with the exception of in situ removal of basal cell carcinoma.
• Any planned major surgery within the duration of the trial.
• Patients who are pregnant, currently breastfeeding, or intend to become pregnant during the course of the trial.
• Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibodies and/or human immunodeficiency virus (HIV).
• After 10 minutes supine rest at the time of screening, any vital signs outside the following ranges:
• Systolic blood pressure (BP): \<90 or \>160 mmHg, or
• Diastolic blood pressure \<50 or \>95 mmHg, or
• Pulse \<40 or \>90 bpm

Sponsors & Collaborators

• Synartro AB: lead
• CTC Clinical Trial Consultants AB: collaborator

Study Sites (1)

Cinical Trial Consultants AB

Uppsala, Sweden

Location

MeSH Terms

Conditions

Osteoarthritis, Knee

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blind-trial
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2025
• First Posted: May 25, 2025
• Study Start: August 19, 2025
• Primary Completion: February 2, 2026
• Study Completion: March 2, 2026
• Last Updated: March 6, 2026

Record last verified: 2026-03

Locations

SE (1)