Explore the safety and efficacy of subretinal administration of CPK850 gene therapy in patients with retinitis pigmentosa caused by mutations in the RLBP1 gene

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

22 Aug 2018 → 13 May 2026

Decision date (initial)

2024-01-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-508688-54-00

EudraCT number

2016-002696-10

ClinicalTrials.gov

NCT03374657

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety, Efficacy

Safety:
- To evaluate the ocular and systemic safety of a single dose of CPK850 in patients with RLBP1 retinitis pigmentosa.
- Ophthalmic safety parameters: best corrected visual acuity (BCVA), intraocular pressure (IOP), slit lamp examination (biomicroscopy), dilated fundus examination, optical coherence tomography (OCT), and color fundus photography (CFP) parameters.
- Systemic safety parameters: adverse events (AEs), blood chemistry, hematology, urinalysis and vital signs.

Efficacy:
To evaluate the recovery of the rod system in eyes treated with CPK850 as compared to pre-treatment assessments.
- Recovery (pre-bleach minus post-bleach values in log10 units) of dark adaptation (DA) at 1-hour post-bleach.
- Pre-bleach DA values (in log10 units).
- Bleaching effect (bleaching minus pre-bleach thresholds in log10 units).
- Dark adaptation kinetics from pre-bleach to 6 hours post-bleach (in log10 units).

Secondary objectives 6

1. To evaluate the recovery of the cone system in eyes treated with CPK850 as compared to pre-treatment assessments.
2. To evaluate the recovery of the rod system in eyes treated with CPK850 as compared to the untreated eye.
3. To evaluate changes from baseline in measures of visual function in eyes treated with CPK850 as compared to pre-treatment assessments as well as to untreated eyes.
4. To evaluate the changes from baseline in the electrical rod and cone system function in eyes treated with CPK850 as compared to pretreatment assessments as well as to untreated eyes.
5. To evaluate the change from baseline in navigation skills in eyes treated with CPK850 as compared to pre-treatment assessments as well as to untreated eyes.
6. To assess the effects of CPK850 on activities of daily living as compared to pre-treatment assessments.

Conditions and MedDRA coding

Retinitis pigmentosa caused by biallelic mutations in the RLBP1 gene

Regulatory references

Scientific advice from competent authorities

Swedish Medical Products Agency, European Medicines Agency

Plan to share IPD

No

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Written informed consent must be obtained before any assessment is performed.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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 9

1. Unable or unwilling to meet requirements of the study
2. History of hypersensitivity to the study drug or to drugs of similar classes or to any of the medications required in the perioperative period.
3. 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.
4. 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.
5. 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.
6. 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.
7. Cerebrovascular accident (stroke) within the 12 months prior to screening at the discretion of the treating physician.
8. 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.
9. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Number of participants with adverse events (AEs), serious adverse events (SAEs) and deaths
2. 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.)

Secondary endpoints 13

1. Number of patients with recovery of the cone system
2. Number of patients with improvement in rod function in the treated eye vs the untreated eye
3. Change from screening/baseline in Visual field perimetry mean deviation
4. Change from screening/baseline in Total contrast sensitivity score
5. Change from screening/baseline in Light-adapted microperimetry sensitivity
6. Change from screening/baseline in Reading speed
7. Change from screening/baseline in the local electrical activity of the retina
8. Change from screening/baseline in eye dominance
9. Change from screening/baseline in mobility test scores
10. Change from screening/baseline in the National Eye Institute -Visual function questionnaire 25 (NEI-VFQ 25) composite score
11. Change from screening/baseline in the low luminance questionnaire (LLQ) responses
12. Change from screening/baseline in the Functional vision questionnaire (FVQ), as available
13. Change from screening/baseline in the electrical activity of the retina

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 8

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 3 files

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

Application history

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