Phase 2b Study of Izokibep in Non-infectious, Intermediate-, Posterior- or Pan-uveitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Acelyrin Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

22 Dec 2022 → 8 Feb 2025

Decision date (initial)

2024-09-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

ACELYRIN, INC., USA

External identifiers

EU CT number

2024-514975-16-00

EudraCT number

2021-006498-49

ClinicalTrials.gov

NCT05384249

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Safety, Dose response, Efficacy

To demonstrate that izokibep is efficacious compared to placebo, as measured by time to treatment failure occurring at or after week 10 and up to week 52

Secondary objectives 1

1. To demonstrate that izokibep is efficacious, as measured by: • Proportion of subjects that achieve quiescence at week 10 • Change in BCVA from best state achieved before week 10 to week 24 • Change in the NEI-VFQ-25 score from best state achieved before week 10 to week 24 • Change in central retinal thickness (by SD-OCT) from baseline to week 10 • Change in central retinal thickness (by SD-OCT) from best state achieved ≤ week 10 up to week 52 2. To assess the safety and tolerability of izokibep as measured by the incidence of TEAEs, events of special interest, SAEs and clinically significant laboratory values and vital signs 3. To assess the immunogenicity of izokibep as measured by the presence of treatment-emergent ADAs"

Conditions and MedDRA coding

Non-infectious, Intermediate-, Posterior- or Pan-uveitis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Subject has provided signed informed consent including consenting to comply with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2. Subject must be ≥ 18 (or the legal age of consent in the jurisdiction in which the study is taking place) and ≤ 75 years of age, at the time of signing the informed consent.
3. Subject is diagnosed with non-infectious intermediate-, posterior- or pan-uveitis.
4. Active disease defined by the presence of at least 1 of the following criteria in at least 1 eye despite treatment with stable doses of corticosteroids for at least 2 weeks prior to day 1: o Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion by dilated indirect ophthalmoscopy, fundus photography, fluorescein angiography (FA), and Spectral-Domain Optical Coherence Tomography (SD OCT) to determine whether a lesion is active or inactive (the central reading center assessment using FA, fundus photography and/or SD-OCT is required to confirm eligibility prior to day 1). o ≥ 2+ vitreous haze (National Eye Institute [NEI]/Standardization of Uveitis Nomenclature [SUN] criteria) by digital indirect ophthalmoscope and fundus photography (the central reading center assessment using fundus photography is required to confirm eligibility prior to day 1)."
5. Currently receiving treatment with oral corticosteroids (≥ 7.5 mg/day to ≤ 40 mg/day oral prednisone/prednisolone or corticosteroid equivalent) at a stable dose for at least 2 weeks prior to day 1.
6. No known history of active tuberculosis (TB).
7. Subject has a negative TB test at screening, as defined by (T-SPOT TB test may be used to establish eligibility if agreed upon with the medical monitor): o Negative QuantiFERON test OR o Negative purified protein derivative (PPD) test (< 5 mm of induration at 48 to 72 hours after test is placed). - Subjects with a positive PPD test and a history of Bacillus Calmette Guerin vaccination will be allowed with a negative QuantiFERON test. - Subjects with a positive or indeterminate QuantiFERON test are allowed if all of the following are satisfied: • No symptoms of TB as determined by investigator. • Documented history of adequate prophylaxis initiation prior to receiving first dose of study drug. • No known exposure to a case of active TB after most recent prophylaxis. • No evidence of active TB on chest radiograph within 3 months prior first dose of study drug."
8. Male and female subjects: Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a. Male subjects: Male subjects are eligible to participate if they agree to the following during the study drug period and for at least 8 weeks after the last dose of study drug: • Refrain from donating fresh unwashed semen. Plus either: o Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR o Must agree to use contraception/barrier as detailed below:  Agree to use a male condom (and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak) when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant. b. Female subjects: • A female subject is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies: o Is a woman of nonchildbearing potential as defined in Section 10.4 (Contraceptive and Barrier Guidance) OR o Is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of < 1%, as described in Section 10.4, during the study drug period and for at least 8 weeks after the last dose of study drug. The investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study drug. • A WOCBP must have a negative highly sensitive serum pregnancy test at screening and negative urine pregnancy test on day 1 prior to the first dose of study drug; see Section 8.2.6.1. "
9. Have demonstrated inadequate response to adalimumab, or for whom adalimumab is contraindicated.

Exclusion criteria 5

1. Disease-related Medical Conditions 1. Subject with isolated anterior uveitis 2. Subject with serpiginous choroidopathy 3. Subject with confirmed or suspected infectious uveitis, including but not limited to infectious uveitis due to TB, syphilis, cytomegalovirus, Lyme disease, toxoplasmosis, human T-lymphotropic virus type 1 infection, Whipple’s disease, herpes zoster virus and herpes simplex virus 4. Subject with corneal or lens opacity that precludes visualization of the fundus or that likely requires cataract surgery during the duration of the study 5. Planned (elective) eye surgery during the course of the study 6. History of prior refractive laser surgery, laser surgery of the macula (including photodynamic therapy or focal laser photocoagulation), retinal laser photocoagulation, or neodymium-doped yttrium aluminum garnet posterior capsulotomy ≤ 30 days before day 1 7. History of any other prior ocular surgery ≤ 3 months prior to day 1 except surgery for cosmetic reasons that is not expected to impact vision 8. Subject with intraocular pressure of ≥ 25 mmHg while on ≥ 2 glaucoma medications or evidence of glaucomatous optic nerve injury 9. Subject with severe vitreous haze that precludes visualization of the fundus prior to first dose of study drug 10. Subject has a contraindication for mydriatic eye drops OR subject cannot be dilated sufficiently well to permit good fundus visualization 11. Subject with BCVA < 20 letters (Early Treatment Diabetic Retinopathy Study [ETDRS]) in at least 1 eye prior to first dose of study drug 12. Subject with proliferative or severe non-proliferative retinopathy or clinically significant macular edema due to diabetic retinopathy 13. Subject with neovascular/wet age-related macular degeneration 14. Subject with an abnormality of the vitreo-retinal interface (eg, vitreomacular traction, epiretinal membranes) with the potential for macular structural damage independent of the inflammatory process 15. Subject with a history of active scleritis ≤ 12 months of first dose of study drug."
2. Other Medical Conditions 16. Active IBD within 3 years prior to enrollment 17. Active infection or history of infection as follows: a. Any active infection for which oral anti-infectives (antibiotics, antivirals, antifungals) were used ≤ 14 days prior to first dose of study drug b. A serious infection requiring hospitalization or IV anti-infectives (antibiotics, antivirals, antifungals) ≤ 30 days prior to first dose of study drug c. Recurrent or chronic infections or other active infections that in the opinion of the investigator might cause this study to be detrimental to the subject 18. Candida infection requiring systemic treatment ≤ 3 months prior to first dose of study drug 19. Removed from the protocol version 2.0 20. Uncontrolled, clinically significant system disease such as diabetes mellitus, hypertension, cardiovascular disease including moderate to severe heart failure (New York Heart Association class III/IV), moderate to severe renal disease, or moderate to severe liver disease, as determined by investigator 21. History of demyelinating disease (including myelitis) or neurological symptoms suggestive of demyelinating disease 22. Malignancy within 5 years except treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, or in situ breast ductal carcinoma 23. History or evidence of any clinically significant disorder, condition or disease that, in the opinion of the investigator, may pose a risk to subject safety or interfere with the study evaluation, procedures or completion 24. Tuberculosis or fungal infection seen on available chest x-ray taken ≤ 3 months of screening or at screening (Exception: documented evidence of completed treatment and clinically resolved) 25. Known history of human immunodeficiency virus (HIV)."
3. Prior/Concomitant Therapy 26. Prior exposure to izokibep or any other IL-17 inhibitor and IL-17 receptor inhibitors (eg, secukinumab, ixekizumab, bimekizumab and brodalumab) 27. Prior exposure to biologics that have a potential for or known association with progressive multifocal leukoencephalopathy (ie, natalizumab [Tysabri®], rituximab [Rituxan®] or efalizumab [Raptiva®]) 28. Exposure to TNF-α inhibitors, IL-1, IL-12, IL-23, IL-12/23 receptor inhibitors or Janus kinase inhibitors within 5 half-lives prior to first dose of study drug 29. Subject on > 1 concomitant non-biologic non-corticosteroid systemic immunosuppressive therapy at baseline and during the study 30. If entering the study on 1 concomitant immunosuppressive therapy, and the dose has not been stable within the last 4 weeks prior to day 1 or is not within the following allowable doses at day 1: o Methotrexate ≤ 25 mg per week (oral or SC) o Cyclosporine ≤ 4 mg/kg/day o Mycophenolate mofetil ≤ 3 mg/day or an equivalent drug to mycophenolate mofetil (eg, mycophenolic acid) at an equivalent dose approved by the medical monitor o Azathioprine ≤ 175 mg/day o Tacrolimus (oral formulation) ≤ 8 mg/day 31. Subject has received Retisert®, Iluvien®, or Yutiq® (glucocorticosteroids implant) ≤ 3 years prior to the first dose of study drug or has had complications related to the device. The subject has had any of these glucocorticosteroids implant removed ≤ 3 months prior to the first dose of study drug or has had complications related to the removal of the device 32. Subject has received intraocular or periocular corticosteroids ≤ 3 months prior to the first dose of study drug 33. Subject has received Ozurdex® (dexamethasone implant) ≤ 6 months prior to the first dose of study drug 34. Subject has received intravitreal methotrexate ≤ 3 months prior to the first dose of study drug 35. Subject has received any of the following intravitreal anti-vascular endothelial growth factor (VEGF) therapy or their biosimilars: o Lucentis® (ranibizumab) or Avastin® (bevacizumab) ≤ 73 days prior to the first dose of study drug o anti-VEGF Trap (aflibercept) ≤ 88 days prior to the first dose of study drug o or within 84 days of baseline for Beovu® (brolucizumab) ≤ 112 days prior to the first dose of study drug 36. Subject on systemic carbonic anhydrase inhibitor ≤ 1 week prior to screening 37. Subject on cyclophosphamide ≤ 30 days prior to the first dose of study drug 38. Any prior or current use of chlorambucil 39. Received live vaccination ≤ 12 weeks prior to dosing or scheduled to receive a live vaccine ≤ 12 weeks following the last dose of study drug 40. Participating in another clinical study or participated in a clinical study involving administration of a study drug within the following time period prior to dosing: 12 weeks, 5 half-lives or twice the duration of the biological effect of the study drug (whichever is longer)"
4. Diagnostic Assessments Laboratory abnormalities and measurements 41. Positive hepatitis B surface antigen (HBsAg) or detected sensitivity on the hepatitis B virus (HBV) DNA polymerase chain reaction (PCR) qualitative test for hepatitis B core antibody (HBcAb)/hepatitis B surface antibody (HBsAb) positive subjects OR positive hepatitis C virus antibody test at screening 42. A positive test for syphilis at screening 43. Laboratory abnormalities at screening: a. Hemoglobin < 9 g/dL b. Platelet count < 100,000/mm3 c. White blood cell count < 3,000 cells/mm3 d. Aspartate aminotransferase and/or alanine aminotransferase ≥ 2.5 times the upper limit of normal e. Moderate or severe renal impairment (ie, creatine clearance < 60 mL/min) (Modification of Diet in Renal Disease [MDRD] formula) Note: Laboratory value(s) out of range due to sampling error or that might be within range after medically appropriate supplementation may be repeated up to 2 times within the screening window before the subject is considered a screen fail. 44. Any other laboratory abnormality that in the opinion of the investigator will pose a risk to subject safety or interfere with the study evaluation, procedures or completion"
5. Other Exclusions 45. History of hypersensitivity or allergy to izokibep or its excipients 46. History of hypersensitivity or allergy to fluorescein dye 47. Previously enrolled, randomized to or withdrawn from this study 48. Active substance abuse (drug or alcohol) within 24 weeks prior to first dose of study drug, as determined by the investigator 49. Any condition that compromises the ability of the subject to give written informed consent, or the subject’s unwillingness or inability to comply with study procedures (ie, subjects who have been placed in an institution on the basis of an official or court order or subject is dependent on the sponsor/investigator or the trial site) 50. History of hypersensitivity to prednisone/prednisolone, or any of its excipients"

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to treatment failure

Secondary endpoints 1

1. • Quiescence • BCVA • NEI-VFQ-25 score • Central retinal thickness • Central retinal thickness • TEAEs, events of special interest and SAEs • Laboratory values and vital signs at collected timepoints • ADAs"

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Acelyrin Inc.

Sponsor organisation

Acelyrin Inc.

Address

4149 Liberty Canyon Road

City

Agoura Hills

Postcode

91301-5146

Country

United States

Scientific contact point

Organisation

Acelyrin Inc.

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

Acelyrin Inc.

Contact name

Clinical Trial Information Desk

Third parties 10

Locations

6 EU/EEA countries · 23 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 34 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