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A First-in-human, Proof of Concept Study of CPK850 in Patients With RLBP1 Retinitis Pigmentosa

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ClinicalTrials.gov Identifier: NCT03374657
Recruitment Status : Recruiting
First Posted : December 15, 2017
Last Update Posted : March 19, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE December 11, 2017
First Posted Date  ICMJE December 15, 2017
Last Update Posted Date March 19, 2021
Actual Study Start Date  ICMJE August 22, 2018
Estimated Primary Completion Date July 28, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 11, 2017)
  • Number of participants with adverse events (AEs), serious adverse events (SAEs) and deaths [ Time Frame: Up to year 5 ]
    Safety events
  • Number of responders in dark adaptation [ Time Frame: Screening/baseline up to year 1 ]
    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 post-treatment visits within one year after treatment.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2017)
  • Number of patients with recovery of the cone system [ Time Frame: Screening/baseline up to year 1 ]
    cone recovery during dark adaptation
  • Number of patients with improvement in rod function in the treated eye vs the untreated eye [ Time Frame: Screening/baseline up to year 1 ]
    rod function during dark adaptation
  • Change from screening/baseline in Visual field perimetry mean deviation [ Time Frame: Screening/baseline up to year 1 ]
    Assessed using automated static perimetry
  • Change from screening/baseline in Total contrast sensitivity score [ Time Frame: Screening/baseline up to year 1 ]
    Contrast sensitivity (ie, the ability to detect relatively dim objects) will be assessed
  • Change from screening/baseline in Light-adapted microperimetry sensitivity [ Time Frame: Screening/baseline up to year 1 ]
    Assessed using standard microperimetry equipment
  • Change from screening/baseline in the local electrical activity of the retina [ Time Frame: Screening/baseline up to year 1 ]
    Assessed using a system designed to record multifocal electroretinogram (ERG) responses from a number of locations at one time
  • Change from screening/baseline in the electrical activity of the retina [ Time Frame: Screening/baseline up to year 1 ]
    Assessed using a system designed to record full-field electroretinogram (ERG) responses with Ganzfeld stimulation.
  • Change from screening/baseline in Reading speed [ Time Frame: Screening/baseline up to year 1 ]
    Assessed using standard reading speed charts
  • Change from screening/baseline in eye dominance [ Time Frame: Screening/baseline up to year 1 ]
    Dominant eye for viewing targets at distance
  • Change from screening/baseline in Change from baseline in mobility test scores [ Time Frame: Screening/baseline up to year 1 ]
    Assessed using a system designed to measure the ability to navigate obstacles in a maze-like environment under varying light conditions
  • Change from screening/baseline in the National Eye Institute - Visual function questionnaire 25 (NEI-VFQ 25) composite score [ Time Frame: Screening/baseline up to year 1 ]
    Questionnaire completed by the participant to measure the influence of visual impairment on quality of life
  • Change from screening/baseline in the low luminance questionnaire (LLQ) responses [ Time Frame: Screening/baseline up to year 1 ]
    Questionnaire completed by the participant to assess visual problems under low luminance conditions, including nighttime
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A First-in-human, Proof of Concept Study of CPK850 in Patients With RLBP1 Retinitis Pigmentosa
Official Title  ICMJE An Open-label First-in-human Single Ascending Dose Study to Explore Safety, Tolerability and Efficacy of Subretinal Administration of CPK850 Gene Therapy in Patients With Retinitis Pigmentosa Due to Mutations in the Retinaldehyde Binding Protein 1 (RLBP1) Gene
Brief Summary The purpose of this first-in-human study is to explore the maximum tolerated dose (MTD) of CPK850 as determined by the single ascending dose ranging portion of the study. This study will also evaluate the safety and potential efficacy of CPK850 on improving visual function in patients with decreased visual function from RLBP1 retinitis pigmentosa due to biallelic mutations in the RLBP1 gene.
Detailed Description This study will potentially include 5 cohorts with a minimum of 3 patients per cohort, with an optional cohort of up to 6 patients. This trial design uses a staggered patient enrollment with continuous data reviews to limit as much unforeseen risk as possible prior to enrolling each patient in each cohort or initiating another cohort. Only one eye (designated as the study or treated eye) will be dosed per patient. Each patient will be followed for 5 years after the subretinal injection of CPK850.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
This is a non-confirmatory, open-label single ascending dose gene replacement-therapy study to assess safety, tolerability and efficacy of CPK850 in patients with RLBP1 retinitis pigmentosa due to biallelic mutations in the RLBP1 gene. The trial design uses a staggered patient enrollment.
Masking: Single (Outcomes Assessor)
Masking Description:

This is a partially masked study. The patients will not be masked. The treating physicians and personnel at the surgical location (surgeons, anesthesiologist, operating room personnel and others) will not be masked.

At the clinical sites, there will be an unmasked ophthalmologist. The remaining assessors at the clinical sites (ophthalmologist, study nurse, ophthalmic technician, etc) doing the ophthalmic examinations should be masked to the study (treated) eye.

The following unmasked sponsor roles are required for this study:

Sponsor clinical staff required to assist in the management and re-supply of investigational drug product.

The independent committee assessing unmasked interim results and the independent analysis team.

All other sponsor staff will stay masked to treatment assignments

Primary Purpose: Treatment
Condition  ICMJE Retinitis Pigmentosa
Intervention  ICMJE Biological: CPK850
In one of 5 dose levels administered via subretinal injection under anesthesia
Study Arms  ICMJE
  • Experimental: CPK Dose 1 (lowest dose)
    CPK850, one subretinal injection to the study eye
    Intervention: Biological: CPK850
  • Experimental: CPK Dose 2 (next lowest dose)
    CPK850, one subretinal injection to the study eye
    Intervention: Biological: CPK850
  • Experimental: CPK Dose 3 (third lowest dose)
    CPK850, one subretinal injection to the study eye
    Intervention: Biological: CPK850
  • Experimental: CPK Dose 4 (next to highest dose)
    CPK850, one subretinal injection to the study eye
    Intervention: Biological: CPK850
  • Experimental: CPK Dose 5 (highest dose)
    CPK850, one subretinal injection to the study eye
    Intervention: Biological: CPK850
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 11, 2017)
15
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 29, 2026
Estimated Primary Completion Date July 28, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male and female patients aged 18 to 70 years inclusive.
  • The visual acuity in the study eye at the screening 1 visit should be no better than 60 ETDRS letters.
  • Clinical diagnosis of Bothnia dystrophy, Newfoundland rod-cone dystrophy or other progressive retinitis pigmentosa phenotype with mutations in the RLBP1 gene verified by genetic testing.
  • Visible photoreceptor (outer nuclear) and Retinal Pigment Epithelium (RPE) layers on standard OCT scan in the study eye at the screening 1 visit.

Exclusion Criteria:

  • History of hypersensitivity to the study drug or to drugs of similar classes or to any of the medications required in the perioperative period.
  • Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints
  • Any contraindication to the planned surgery or anesthesia as determined by the treating physician (surgeon, anesthesiologist, internist, or designee).
  • Women who are pregnant, or lactating or women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for two months after treatment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals
Listed Location Countries  ICMJE Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03374657
Other Study ID Numbers  ICMJE CCPK850X2202
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
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 trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP