Efficacy and Safety Evaluation of Izokibep in Patients with Non-infectious Intermediate, Posterior, or Pan-uveitis: A Phase 2b Randomized Controlled Trial
- Trial ID
- 2024-514975-16-00
- Protocol
- 21103
- Sponsor
- Acelyrin Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to demonstrate the efficacy of **izokibep** compared to placebo in subjects with non-infectious, intermediate-, posterior-, or pan-uveitis. This is measured by the time to treatment failure occurring at or after week 10 and up to week 52. This objective is clinically relevant as it aims to establish the therapeutic potential of izokibep in managing a condition that can lead to significant visual impairment if not effectively treated.
Secondary objectives include:
- Demonstrating the efficacy of izokibep by assessing the proportion of subjects achieving quiescence at week 10, changes in best-corrected visual acuity (BCVA) and NEI-VFQ-25 score from the best state achieved before week 10 to week 24, and changes in central retinal thickness (measured by SD-OCT) from baseline to week 10 and from the best state achieved ≤ week 10 up to week 52.
- Assessing the safety and tolerability of izokibep by monitoring the incidence of treatment-emergent adverse events (TEAEs), events of special interest, serious adverse events (SAEs), and clinically significant laboratory values and vital signs.
- Evaluating the immunogenicity of izokibep by detecting the presence of treatment-emergent anti-drug antibodies (ADAs).
Participants
The clinical trial involves a total of **75 participants** diagnosed with **non-infectious intermediate-, posterior-, or pan-uveitis**. The study population includes both male and female subjects, aged between 18 and 75 years. Participants were selected based on specific inclusion criteria, including the presence of active disease despite treatment with stable doses of corticosteroids and a negative tuberculosis test. The trial population is characterized by individuals who have demonstrated an inadequate response to adalimumab or for whom adalimumab is contraindicated. Participants are required to maintain stable corticosteroid treatment and adhere to contraceptive guidelines as per local regulations. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, ensuring comprehensive monitoring and adherence to ethical standards.
Plans and Procedures
The clinical trial is designed to evaluate the **efficacy** and safety of **izokibep** in subjects diagnosed with non-infectious, intermediate-, posterior-, or pan-uveitis. This is a Phase 2b pivotal study employing a randomized, double-blind, placebo-controlled design. The trial aims to compare the time to treatment failure between the active treatment group receiving izokibep and the placebo group. The study is expected to span approximately 52 weeks, with participant involvement lasting up to 51 weeks.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as age, diagnosis, and current treatment regimen. The screening process will include assessments like dilated indirect ophthalmoscopy, fundus photography, and fluorescein angiography to verify active disease presence. Following successful screening, participants will be randomized to receive either izokibep or placebo via subcutaneous injection. Subsequent follow-up visits will occur at regular intervals to monitor treatment response, safety, and any adverse events. These visits will include evaluations of quiescence, best-corrected visual acuity (BCVA), and central retinal thickness, among other parameters.
The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted to gather comprehensive data on the primary and secondary endpoints. Participants may be withdrawn from the study prematurely if they experience significant adverse events, fail to comply with study protocols, or if the investigator deems it necessary for their safety. The trial's primary endpoint is the time to treatment failure, while secondary endpoints include measures such as NEI-VFQ-25 score, treatment-emergent adverse events (TEAEs), and laboratory values. The study is not classified as low intervention and is conducted under the sponsorship of ACELYRIN, INC.
Treatment
The clinical trial involves the administration of **Izokibep**, a solution for injection, as the experimental medication. Izokibep is a protein-based therapeutic agent developed by ACELYRIN, INC. The pharmaceutical form of Izokibep is a solution for injection, and it is administered subcutaneously. The maximum daily dose is 160 mg, with a total maximum dose of 160 mg over the treatment period. The treatment period extends up to 51 weeks. The administration schedule and dosing frequency are determined based on the study protocol, and participant compliance is monitored throughout the trial to ensure adherence to the dosing regimen.
The trial also includes a placebo group, which receives the ABY-035 Formulation Buffer (FB) as a comparator treatment. This formulation buffer consists of 10 mM Sodium Phosphate, 150 mM NaCl, and 0.5 mM EDTA at pH 7.0. It is intended for parenteral administration and serves as the placebo for Izokibep in the clinical trial. The placebo is administered in a manner consistent with the experimental treatment to maintain blinding and ensure the integrity of the study results. Compliance with placebo administration is similarly monitored to ensure consistency and reliability of the trial data.
Efficacy
The efficacy of Izokibep in the treatment of non-infectious intermediate-, posterior-, or pan-uveitis will be assessed through a Phase 2b pivotal study. The primary endpoint for evaluating efficacy is the **time to treatment failure**, which will be measured from week 10 up to week 52. Secondary endpoints include quiescence, Best Corrected Visual Acuity (BCVA), NEI-VFQ-25 score, central retinal thickness, treatment-emergent adverse events (TEAEs), events of special interest, serious adverse events (SAEs), laboratory values, vital signs, and anti-drug antibodies (ADAs).
Data collection will involve various validated tools and methods, including dilated indirect ophthalmoscopy, fundus photography, fluorescein angiography (FA), and Spectral-Domain Optical Coherence Tomography (SD OCT) to assess active lesions. The central reading center will confirm eligibility and assess disease activity using these imaging techniques. The schedule for measuring these parameters will align with the study's timeline, ensuring comprehensive data collection at specified intervals to evaluate the efficacy of the treatment accurately.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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.
- 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.
- Subject is diagnosed with non-infectious intermediate-, posterior- or pan-uveitis.
- 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)."
- 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.
- No known history of active tuberculosis (TB).
- 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."
- 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. "
- Have demonstrated inadequate response to adalimumab, or for whom adalimumab is contraindicated.
Exclusion Criteria
- 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."
- 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)."
- 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)"
- 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"
- 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"
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Recruiting | 29 Jun 2022 | 3 |
 Czechia | Not Recruiting | 29 Jun 2022 | 3 |
 France | Not Recruiting | 29 Jun 2022 | 2 |
 Germany | Not Recruiting | 29 Jun 2022 | 2 |
 Italy | Not Recruiting | 29 Jun 2022 | 4 |
 Spain | Not Recruiting | 29 Jun 2022 | 7 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
The ABY-035 Formulation Buffer (FB) 10 mM Sodium Phosphate, 150 mM NaCl, and 0.5 mM EDTA at pH 7.0 is intended to be used for parenteral administration as Placebo of izokibep (ABY-035) in clinical trials. | Placebo | N/A | — | — | — | N/A |
Izokibep | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS | 160 | 51 | PRD9752440 |