Clinical trial NCT06626971: The Use of ARA290 for the Treatment of Diabetic Macular Oedema
Official title: A Phase II Clinical Trial on the Use of ARA 290 for the Treatment of Diabetic Macular Oedema
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Diabetic Macular Oedema
Lead sponsor: Belfast Health and Social Care Trust
Sponsor class: OTHER
Collaborators: name: Araim Pharmaceuticals, Inc.
First posted: 2024-10-04
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: ARA 290-DMO is a prospective, open label, interventional, single centre, investigator led, phase II trial to examine the effect of ARA 290 on diabetic macular oedema in patients with type 1 or 2 diabetes.

The aim or primary objective of the study was to determine whether ARA 290 administered at a daily dose of 4mg subcutaneously for 12 weeks to patients with diabetes mellitus (DM) and DMO would have a beneficial effect on mean change in best corrected visual acuity (BCVA) from baseline values to week 12.

Detailed description: Diabetic retinopathy a very most common cause of sight loss in people of working age. Sight loss occurs in diabetes because of diabetic macular oedema (DMO) and/or proliferative diabetic retinopathy (PDR), both are complications of diabetes in the eye.

In DMO fluid accumulates in the macula, the area responsible for our central sight. As the fluid accumulates the sight drops. The current treatments for DMO include laser and anti VEGF drugs and steroids. Anti VEGF drugs have been very helpful in the treatment of DMO. However, anti VEGF drugs need to be given by an injection into the eye, an Ophthalmologist (eye specialist) or a specialist nurse (a nurse trained for this purpose) will need to deliver this treatment to patients with DMO in the hospital.

Furthermore, patients require injections every four weeks during the first months of treatment and long term treatment is required. Moreover, not all patients respond to anti VEGFs: In 40% of patients the sight may not improve despite these injections. Because many patients with DMO have DMO in both eyes, injections need to be given in both eyes to many patients.

Given the above facts there appeared a clear need to develop new treatments for people with DMO. ARA 290 is a drug that has marked anti-inflammatory properties and has an effect in preventing the death of cells. As inflammation is known to play a role in the occurrence of DMO, it was thought that ARA 290 could potentially be helpful in treating patients with this condition. In light of this, the Investigators carried out this study to find out if ARA 290 was effective in drying the fluid in DMO. If this treatment was successful, benefits may have included a reduction of the demands on health care services and patient benefits of: self administration of the drug at home by the patients; a reduction in hospital visits; treatment of both eyes at once, reduced risks associated with injections; a more pleasant treatment (subcutaneous injection versus an injection into the eye).

Eligibility criteria: Inclusion Criteria:

1. Patients with DR and centre involving DMO with a central subfield thickness of \> 400 microns, as determined using SD-OCT;
2. \>= 18 years of age
3. Clear media and naïve to previous treatments for DMO.

Exclusion Criteria:

1. Macular oedema related to other retinal disease
2. Hazy media that prevents adequate retinal imaging
3. Allergy to fluorescein
4. Previous treatments for DMO
5. DMO with central subfield thickness of \< 400 microns
6. Patients on systemic or topical steroids
7. Use of erythropoiesis stimulating agents within the two months prior to screening or during the trial
8. Treated with any other investigational medication or device within 60 days
9. Pregnant women, women who have not yet reached the menopause (no menses for 12 months or more without an alternative medical cause) who test positive for pregnancy or who are unwilling to take a pregnancy test prior to trial entry or are unwilling to undertake adequate precautions to prevent pregnancy for the duration of the trial.
10. Men who have a female partner and who are unwilling to undertake adequate precautions to prevent pregnancy for the duration of the trial.
11. Female patients who are breastfeeding
12. Active proliferative diabetic retinopathy (PDR) requiring treatment.
13. Patients with other eye diseases besides DR
14. Patients who are unable or unwilling to commit to the study schedule of events
15. Serious illness that is likely to affect the patient's ability to complete the study

Any patient showing a clinically significant improvement between the initial screening and presenting for the first screening/baseline visit may no longer be eligible for the study and will be recorded as a screen failure and will not be entered on to the study.

Primary outcomes:
measure: Primary Outcome - Best corrected distance visual acuity.
timeFrame: From baseline to week 12 (+/- 7 days)
Secondary outcomes:
measure: Secondary Outcome - Central subfield thickness
timeFrame: Changes from baseline to week 12 (+/- 7 days).
measure: Secondary Outcome - Central retinal sensitivity
timeFrame: Changes from baseline to week 12 (+/- 7 days)
measure: Secondary Outcome - Retinal perfusion
timeFrame: Changes from baseline to week 12 (+/- 7 days)
measure: Secondary Outcome - Tear production
timeFrame: Changes from baseline to week 12 (+/- 7 days)
measure: Secondary Outcome - Patient reported outcome
timeFrame: Changes from baseline to week 12 (+/- 7 days)
measure: Secondary Outcome - Change in inflammatory markers
timeFrame: Changes from baseline to week 12 (+/- 7 days)
measure: Secondary Outcome - Number of Adverse events
timeFrame: Changes from baseline to week 12 (+/- 7 days)
measure: Secondary Outcome -% of participants with ≥ 15 ETDRS letter gain
timeFrame: baseline to week 12
measure: Secondary Outcome -% of participants with ≥ 10 ETDRS letter gain
timeFrame: baseline to week 12
measure: Secondary Outcome - Patient reported outcomes
timeFrame: Changes from baseline to week 12 (+/- 7 days)
measure: Secondary Outcome - Change in glycosylated albumin
timeFrame: Changes from baseline to week 12 (+/- 7 days)
measure: Secondary Outcome - Change in carbamylated albumin
timeFrame: Changes from baseline to week 12 (+/- 7 days)
Other outcomes:
measure: Exploratory Outcome - Change in Adenosine Deaminase (ADA)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome - Change in Artemin (ARTN)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome - Axin-1 (AXIN1)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome - Beta-nerve growth factor (BDNF)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome - Caspase 8 (CASP-8)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome - C-C motif chemokine 4 (CCL4)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome - C-C motif chemokine 19 (CCL19)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome - C-C motif chemokine 20 (CCL20)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome - C-C motif chemokine 25 (CCL25)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome - C-C motif chemokine 28 (CCL28)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome - CD40L receptor (CD40)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome - CUB domain-containing protein 1 (CDCP1)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome - C-X-C motif chemokine 1 (CXCL1)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome - C-X-C motif chemokine 5 (CXCL5)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -C-X-C motif chemokine 6 (CXCL6)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -C-X-C motif chemokine 9 (CXCL9)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -C-X-C motif chemokine 10 (CXCL10)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -C-X-C motif chemokine 11 (CXCL11)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Cystatin D (CST5)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Delta and Notch-like epidermal growth factor related recep (DNER)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Eotaxin-1 (CCL11)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -karyotic translation initiation factor 4Ebinding protein 1 (4E-BP1)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Fibroblast growth factor 5 (FGF-5)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Fibroblast growth factor 19 (FGF-19)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Fibroblast growth factor 21 (FGF-21)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Fibroblast growth factor 23 (FGF-23)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Fms-related tyrosine kinase 3 ligand (Flt3L)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Fractalkine (CX3CL1)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Glial cell line-derived neurotrophic factor (hGDNF)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Hepatocyte growth factor (HGF)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interferon gamma (IFN-gamma)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interleukin-1 alpha (IL-1 alpha)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interleukin-2 (IL-2)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interleukin-2 receptor subunit beta (IL-2RB)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interleukin-4 (IL-4)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interleukin-5 (IL-5)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interleukin-6 (IL-6)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interleukin-7 (IL-7)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interleukin-8 (IL-8)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interleukin-10 (IL-10)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interleukin-10 receptor subunit alpha (IL-10RA)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interleukin-10 receptor subunit beta (IL-10RB)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interleukin-12 subunit beta (IL-12B)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interleukin-13 (IL-13)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -interleukin-15 receptor subunit alpha (IL-15RA)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interleukin-17A (IL-17A)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interleukin-17C (IL-17C)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interleukin-20 (IL-20)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interleukin-20 receptor subunit alpha (IL-20RA)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interleukin-23 (IL-24)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interleukin-22 receptor subunit alpha-1 (IL-22 RA1)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Interleukin-33 (IL-33)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Latency-associated peptide transforming growth factor beta 1 (LAP TGF-beta-1)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Leukemia inhibitory factor receptor (LIF-R)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Macrophage colony-stimulating factor 1 (CSF-1)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Macrophage inflammatory protein 1-alpha (MIP1 alpha)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Matrix metalloproteinase-1 (MMP-1)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Matrix metalloproteinase-10 (MMP-10)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Monocyte chemotactic protein 1 (MCP-1)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Monocyte chemotactic protein 2 (MCP-2)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Monocyte chemotactic protein 3 (MCP-3)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Monocyte chemotactic protein 4 (MCP-4)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Natural killer cell receptor 2B4 (CD244)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Neurotrophin-3 (NT-3)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Neurturin (NRTN)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Oncostatin-M (OSM)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Osteoprotegerin (OPG)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Programmed cell death 1 ligand 1 (PD-L1)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Protein S100-A12 (EN-RAGE)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Signaling lymphocytic activation molecule (SLAMF1)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -SIR2-like protein 2 (SIRT2)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -STAM-binding protein (STAMPB)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Stem cell factor (SCF)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Sulfotransferase 1A1 (ST1A1)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -T-cell surface glycoprotein CD5 (CD5)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -T cell surface glycoprotein CD6 isoform (CD6)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Thymic stromal lymphopoietin (TSLP)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -TNF-beta (TNFB)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -TNF-related activation-induced cytokine (TRANCE)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -TNF-related apoptosis-inducing ligand (TRAIL)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Transforming growth factor alpha (TGF-alpha)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Tumor necrosis factor (ligand) superfamily, member 12 (TWEAK)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Tumor necrosis factor (TNF)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Tumor necrosis factor ligand superfamily member 14 (TNFSF14)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Tumor necrosis factor ligand superfamily member 9 (TNFSF9)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Urokinase-type plasminogen activator (uPA)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome -Vascular endothelial growth factor A (VEGF-A)
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome - Carbamylated albumin
timeFrame: Baseline to week 12 (+/- 7 days)
measure: Exploratory Outcome - Glycosylatedalbumin
timeFrame: Baseline to week 12 (+/- 7 days)
Locations:
city: Belfast
country: United Kingdom
facility: Belfast Health & Social Care Trust
state: Co Antrim
Study officials:
affiliation: Belfast Health & Social Care Trust and Queen's University Belfast
name: Noemi Lois
role: STUDY_CHAIR
References: