A prospective, double-blinded, randomized, placebo-controlled phase 1/2a study to assess safety, tolerability, systemic exposure and preliminary efficacy of single intraarticular injections of three dose levels of SYN321 and placebo in patients with symptomatic knee osteoarthritis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Synartro AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

19 Aug 2025 → 2 Feb 2026

Decision date (initial)

2024-10-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-517920-21-00

EudraCT number

2022-003633-19

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Safety, Efficacy

To evaluate the safety and tolerability of SYN321 after single IA injection in patients with symptomatic KOA. Three (3) dose levels of SYN321 will be evaluated.

Secondary objectives 2

1. To determine the systemic exposure of diclofenac, linker (and linker associated metabolites), and diclofenac lactam (break down products from SYN321).
2. To assess the preliminary efficacy following single IA injections of SYN321 at 3 dose levels in patients with symptomatic KOA.

Conditions and MedDRA coding

knee osteoarthritis

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Swedish Medical Products Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 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.
2. Male or female patient clinically diagnosed with KOA, who have received the diagnosis at least 3 months prior to Visit 1. The KOA diagnosis should be confirmed in the patient’s medical record.
3. Dominant pain in one knee due to KOA between 4 and 8 inclusive on the NRS scale (0-10) with weight bearing pain when walking on a flat surface, at the time of inclusion (checked at screening [Visit 1] and confirmed at Visit 2, pain during the last 7 days).
4. Age 40 to 79 years, inclusive at the time of Visit 1.
5. Body mass index (BMI) ≥ 18.5 and < 35.0 kg/m2.
6. 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.)
7. 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).
8. 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.
9. 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]). Female sterilization 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.
10. Patients without contraindications for treatment with diclofenac.

Exclusion criteria 25

1. 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.
2. Previous IA fracture of the knee.
3. 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.
4. IA injections of steroids or HA or other invasive procedure (e.g., arthroscopy, arthrography, surgery) in the knee within 3 months prior to screening.
5. Conditions or medications that could confound the assessment of pain, as judged by the Investigator.
6. Conditions that could be adversely affected by an IA injection (e.g., eczema, skin infection, high bleeding risk etc.), as judged by the Investigator.
7. Any clinically significant illness (except KOA), medical/surgical procedure, or trauma within 4 weeks of the administration of IMP.
8. Malignancy within the past 5 years, with the exception of in situ removal of basal cell carcinoma.
9. Any planned major surgery within the duration of the trial.
10. Patients who are pregnant, are currently breastfeeding, or intend to become pregnant during the course of the trial.
11. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibodies and/or human immunodeficiency virus (HIV).
12. 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
13. Prolonged QTcF (> 450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the Investigator.
14. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to SYN321, including disinfectants and adhesives or hypersensitivity to acetylsalicylic acid.
15. History of asthma, angioedema, urticaria or acute rhinitis induced by NSAID, including acetylsalicylic acid.
16. Regular use of any prescribed or non-prescribed medications, including but not limited to antacids, analgesics, herbal remedies, vitamins and minerals, within 10 days prior to the first administration of IMP, as well as nasal decongestants without cortisone, antihistamine, or anticholinergics for a maximum of 10 days, at the discretion of the Investigator. Regular use of other medications may be permitted if, in the Investigator’s judgment, they do not place the patient at risk or interfere with trial results. For intake of allowed medications and rescue medication and others, refer to Section 9.6.2.2 and 9.6.2.3.
17. Patient has taken pain medication or has received pain medicine other than paracetamol for conditions unrelated to KOA of the index knee within 10 days prior to the injection.
18. Planned treatment or treatment with another investigational drug within 3 months prior to Day 1. Patients consented and screened but not dosed in previous phase 1 studies will not be excluded.
19. Current smokers or users of nicotine products. Irregular use of nicotine (e.g., smoking, snuffing, chewing tobacco) less than 3 times/week before the screening visit will be allowed.
20. Positive screen for drugs of abuse or alcohol at screening. Positive results that are expected given the patient’s medical history and prescribed medications can be disregarded as judged by the Investigator.
21. History of or current alcohol abuse or excessive intake of alcohol, as judged by the Investigator.
22. History of or current drug abuse, as judged by the Investigator.
23. History of or current use of anabolic steroids, as judged by the Investigator.
24. Plasma donation within 1 month of screening or blood donation (or corresponding blood loss) during the last 3 months prior to screening.
25. The Investigator considers the patient unlikely to comply with trial procedures, restrictions, and requirements.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Frequency, seriousness, and intensity of AEs.
2. Clinically significant changes in electrocardiogram (ECG), vital signs, safety laboratory measurements (hematology, clinical chemistry, coagulation), physical examination findings and local tolerability.

Secondary endpoints 4

1. Concentration of diclofenac, linker (and linker associated metabolites) and diclofenac lactam in plasma and urine. Concentrations in urine will be assessed in an exploratory manner. The following pharmacokinetic (PK) parameters will be explored: maximum plasma concentration (Cmax) and area under the plasma concentration vs. time curve (AUC) Additional PK parameters may be explored if deemed appropriate.
2. Self-registered pain using the NRS (0-10) once daily every day until Day 56. NRS sum of pain intensity difference (SPID) for current pain in the index knee will be analyzed for all time points measured.
3. Self-registered function and quality of life using Knee Injury and Osteoarthritis Outcome Score (KOOS). Change from baseline in average sum of KOOS scores, KOOS subscale scores.
4. Use of rescue medication.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Synartro AB

Sponsor organisation

Synartro AB

Address

Dalgatan 16 A, Uppsala Domkyrkofors Uppsala Domkyrkofors

City

Uppsala

Postcode

752 18

Country

Sweden

Scientific contact point

Organisation

Synartro AB

Contact name

Antonio Bermejo Gomez

Public contact point

Organisation

Synartro AB

Contact name

Magnus Hurst

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications