CPK850 for Retinitis pigmentosa (RLBP1-associated)

Inclusion criteria

• {"criterion_text":"- Written informed consent must be obtained before any assessment is performed.\n- Male and female patients aged 18 to 70 years. All female patients must have negative pregnancy test results at the screening visits and just prior to the treatment day.\n- The patients must have sufficiently clear ocular media and adequate pupil dilation to permit fundus photographs of adequate clarity and performance of vitrectomy and subretinal injection.\n- Patients must meet surgical requirements. In addition, patients must weigh at least 40 kg to participate in the study, and must have a body mass index (BMI) <40 kg/m2. BMI = Body weight (kg) / [Height (m)]2.\n- The visual acuity in the study eye at the screening 1 visit should be no better than 60 early treatment diabetic retinopathy study (ETDRS) letters. In Cohort 1, patients with visual acuity from 35 ETDRS letters to Hand Motion visual acuity will be included. For Cohorts 2 and beyond, patients with visual acuity of 60 ETDRS letters to Hand Motion visual acuity will be enrolled. Consideration for inclusion in Cohorts 1 and 2 only may be given to patients with visual acuity as low as Light Perception at the screening 1 visit, if they meet all other inclusion/exclusion criteria and at the agreement of the sponsor and principal investigators.\n- Clinical diagnosis of Bothnia dystrophy, Newfoundland rod-cone dystrophy or other progressive retinitis pigmentosa phenotype with biallelic mutations in the RLBP1 gene verified by Clinical Laboratory Improvement Amendments (CLIA), Good Laboratory Practices (GLP) or equivalent molecular genetics testing.\n- Visible photoreceptor (outer nuclear) and retinal pigment epithelium (RPE) layers on standard OCT scan in the study eye at the screening 1 visit as confirmed by the Central Reading Center.\n- Dark adaptation bleaching effect in the study eye at short wavelength stimulus of > 1.0 log unit at 2 of the 3 baseline measures obtained prior to treatment."}

Exclusion criteria

• {"criterion_text":"- Unable or unwilling to meet requirements of the study\n- History of hypersensitivity to the study drug or to drugs of similar classes or to any of the medications required in the perioperative period.\n- Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints; for example: glaucoma (IOP ≥25 mm Hg despite treatment with anti-glaucoma medication or low tension glaucoma), corneal or significant lenticular opacities, retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization of any cause.\n- Any active infection or ocular disease involving ocular adnexa including infectious conjunctivitis, keratitis, scleritis, endophthalmitis, as well as idiopathic or autoimmune-associated uveitis in either eye.\n- Any contraindication to the planned surgery or anesthesia as determined by the treating physician (surgeon, anesthesiologist, primary care physician or designee). Use of systemic anticoagulant therapies during the study, such as warfarin, heparin or similar are to be evaluated by the treating physician as potential exclusions. The use of aspirin is not usually an exclusion criterion unless indicated by the treating physician. Abnormal vital signs and/or Electrocardiograms (ECGs) that suggest potential contraindications for planned study anesthesia are exclusions.\n- Known history of or current clinically significant arrhythmias, myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI) within 6 months prior to screening or patients with heart failure New York Heart Association (NYHA) class IIIV at the discretion of the treating physician or cardiologist.\n- Cerebrovascular accident (stroke) within the 12 months prior to screening at the discretion of the treating physician.\n- Complicating systemic diseases or clinically significant abnormal laboratory values. Complicating systemic diseases would include those in which the disease itself, or the treatment for the disease, can alter ocular function. Examples are malignancies whose treatment could affect central nervous system function (for example radiation treatment of the orbit; leukemia with central nervous system (CNS)/optic nerve involvement). Also patients with immunocompromising diseases would be excluded since they would have susceptibility to opportunistic infections.\n- Women who are pregnant or nursing (lactating), as well as male and female patients of childbearing potential that are unwilling to use contraception as per study requirements."}

Primary endpoints

• {"endpoint_text":"- Number of participants with adverse events (AEs), serious adverse events (SAEs) and deaths","definition_or_measurement_approach":"Count of participants experiencing AEs, SAEs, and deaths as recorded during study assessments (safety monitoring: ocular and systemic safety parameters including AEs, blood chemistry, hematology, urinalysis and vital signs)."}
• {"endpoint_text":"- Number of responders in dark adaptation (A patient is considered a responder if sensitivity recovery values at 1-hour post-bleach are observed to be outside of the patient's prediction interval at ≥2 consecutive posttreatment visits within one year after treatment.)","definition_or_measurement_approach":"Responder definition provided in parentheses: a patient is a responder if sensitivity recovery values at 1-hour post-bleach are outside the patient's prediction interval at ≥2 consecutive posttreatment visits within one year after treatment; measurement based on dark adaptation testing (pre-bleach and post-bleach values in log10 units)."}

Secondary endpoints

• {"endpoint_text":"- Number of patients with recovery of the cone system","definition_or_measurement_approach":"Recovery assessed by cone system function measures compared to pre-treatment assessments."}
• {"endpoint_text":"- Number of patients with improvement in rod function in the treated eye vs the untreated eye","definition_or_measurement_approach":"Improvement measured by rod function assessments comparing treated versus untreated eye."}
• {"endpoint_text":"- Change from screening/baseline in Visual field perimetry mean deviation","definition_or_measurement_approach":"Change from baseline in visual field perimetry mean deviation compared to screening."}
• {"endpoint_text":"- Change from screening/baseline in Total contrast sensitivity score","definition_or_measurement_approach":"Change from baseline in total contrast sensitivity score."}
• {"endpoint_text":"- Change from screening/baseline in Light-adapted microperimetry sensitivity","definition_or_measurement_approach":"Change from baseline in light-adapted microperimetry sensitivity."}
• {"endpoint_text":"- Change from screening/baseline in Reading speed","definition_or_measurement_approach":"Change from baseline in reading speed assessments."}
• {"endpoint_text":"- Change from screening/baseline in the local electrical activity of the retina","definition_or_measurement_approach":"Change from baseline in local retinal electrical activity (electrophysiology measures)."}
• {"endpoint_text":"- Change from screening/baseline in eye dominance","definition_or_measurement_approach":"Change from baseline in assessments of eye dominance."}
• {"endpoint_text":"- Change from screening/baseline in mobility test scores","definition_or_measurement_approach":"Change from baseline in mobility test scores."}
• {"endpoint_text":"- Change from screening/baseline in the National Eye Institute -Visual function questionnaire 25 (NEI-VFQ 25) composite score","definition_or_measurement_approach":"Change from baseline in NEI-VFQ-25 composite score."}
• {"endpoint_text":"- Change from screening/baseline in the low luminance questionnaire (LLQ) responses","definition_or_measurement_approach":"Change from baseline in LLQ responses."}
• {"endpoint_text":"- Change from screening/baseline in the Functional vision questionnaire (FVQ), as available","definition_or_measurement_approach":"Change from baseline in FVQ scores, when available."}
• {"endpoint_text":"- Change from screening/baseline in the electrical activity of the retina","definition_or_measurement_approach":"Change from baseline in whole-retina electrical activity (electrophysiology measures)."}

Sweden

Earliest CTIS Part Ii Submission Date

29-11-2023

Latest Decision Or Authorization Date

19-01-2024

Processing Time Days

51

Number Of Sites

1

Number Of Participants

21

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Parexel International (IRL) Limited

Responsibilities

sponsorDuties code: 12; contact email: Clinical.Enquiries@parexel.com

Name

Parexel International Corp.

Responsibilities

Ancillary supplies

Name

Ora Inc.

Responsibilities

Mobility vendor and reading center

Third parties

• {"country":"United Kingdom","full_name":"Labcorp Early Development Laboratories Limited","duties_or_roles":"sponsorDuties codes: 10,8","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"sponsorDuties codes: 12; contact email: Clinical.Enquiries@parexel.com","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"ClinBay SPRL.","duties_or_roles":"sponsorDuties codes: 10","organisation_type":"SME"}
• {"country":"United States","full_name":"Actigraph LLC","duties_or_roles":"Activity monitoring vendor","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Duke Reading Center","duties_or_roles":"Reading Center","organisation_type":"SME"}
• {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"Ancillary supplies","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Ora Inc.","duties_or_roles":"Mobility vendor and reading center","organisation_type":"Pharmaceutical company"}
• {"country":"Sweden","full_name":"Apoteket AB","duties_or_roles":"sponsorDuties codes: 14","organisation_type":"Pharmaceutical company"}