Safety and Efficacy of CRISPR/Cas9 mRNA Instantaneous Gene Editing Therapy to Treat Refractory Viral Keratitis

NCT04560790 | Completed DMC

• 1 other identifier: JYMS-CXL#02
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety, tolerability and efficacy of a single escalating doses of BD111 CRISPR/Cas9 mRNA Instantaneous Gene Editing Therapy administered via corneal injection in participants with refractory herpetic viral keratitis.

Conditions

Viral Keratitis; Blindness Eye; Herpes Simplex Virus Infection; Cornea

Keywords

Herpes simplex virus type 1 (HSV-1); CRISPR/Cas9 mRNA; instantaneous gene editing

Outcome Measures

Primary Outcomes (3)

• Effective clearance of HSV-1 genome

  Judge HSV-1 genome clearance effective according to DNA sequencing results by methods of Plaque assay,Elisa,PCR etc.

  12 months

• Rate of reblindness in 3 participants with Refractory HSV Keratitis

  180 days after corneal surgical, calculate rate of reblindness of treated eye in 3 participants.

  12 months

• HSV-1 virus testing outcome of the intervention eye

  Herpes virus content before and after treatment were determinated by methods of plaque assay, ELISA, PCR etc. Compare the viral content changes with baseline.

  12 months

Secondary Outcomes (4)

• Corneal graft survival time

  12 months

• Visual improvement compared with baseline

  12 months

• Concentration of dose limiting toxicities

  12 months

• Concentration of maximum tolerated dose

  12 months

Study Arms (1)

BD111 Adults single group Dose

EXPERIMENTAL

Administered by corneal injection surgery. Dosage form:injection solution. Dose:200uL. Frequency of administration: one time injection.

Drug: BD111 Adult single group Dose

Interventions

BD111 Adult single group Dose DRUG

3-6 Participants will receive a single group dose administered via corneal injection in the study eye.

BD111 Adults single group Dose

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients (replase) with refractory keratitis caused by herpes virus type I who has had at least one time failed corneal transplant.
• Age between 18 to 70 years.
• No systemic immune eye disease.
• Good eyelid structure and blink function.
• Exists the potential of visual recovery by evaluation of ocular structure and function.
• Patients with refractory keratitis who are repeatedly infected with HSV-1 virus (more than three times per year) and resistant to topical or systemic anti-viral agents, with no response to regular immunosuppressive agents.
• Patients who are obviously suffering from relapse HSV infections with corneal perforation, requiring corneal transplantation;
• No history of corneal trauma.
• Subjects or their legal guardians voluntarily participate in this study, sign informed consent, good compliance and cooperation with follow-up visits.

You may not qualify if:

• Lacrimal coating and blink function loss.
• Schirmer's test result is less than 2mm for severe dry eye disease.
• Pregnant and lactating women (pregnancy defined in this study as positive urine pregnancy test).
• Currently is involved in clinical trials of other drugs or medical devices.
• Active eye infection (including but not limited to: blepharitis, infectious conjunctivitis, keratitis, sclerotitis, endophthalmitis) in target eye or contralateral eye within 30 days prior to enrollment.
• Ocular surface malignant tumor.
• A history of allergic reaction or allergy to sodium luciferin, allergy to protein products used for treatment or diagnosis, allergy to ≥ 2 drugs or non-drug factors, or current allergic disease.
• current in an infectious disease requiring oral, intramuscular or intravenous administration.
• Patients with systemic immune diseases.
• Any uncontrolled clinical problems (such as severe mental, neurological, cardiovascular, respiratory and other systemic diseases and malignant neoplasms).
• Not effective contraception.
• In uncontrolled hypertension, systolic is no less than 160 mmhg, diastolic is no less than 100 mmhg.
• In uncontrolled diabetes, fasting glucose is no less than 10.0umol/L.
• Renal insufficiency, serum creatinine is more than 133umol/L.
• Arrhythmia, myocardial ischemia, myocardial infarction (diagnosed by electrocardiogram).

Sponsors & Collaborators

• Shanghai BDgene Co., Ltd.: lead
• Eye & ENT Hospital of Fudan University: collaborator

Study Sites (1)

Eye & Ent Hospital of Fudan University

Shanghai, Shanghai Municipality, 200000, China

Location

Related Publications (1)

• Wei A, Yin D, Zhai Z, Ling S, Le H, Tian L, Xu J, Paludan SR, Cai Y, Hong J. In vivo CRISPR gene editing in patients with herpetic stromal keratitis. Mol Ther. 2023 Nov 1;31(11):3163-3175. doi: 10.1016/j.ymthe.2023.08.021. Epub 2023 Aug 31.

  PMID: 37658603 DERIVED

MeSH Terms

Conditions

Blindness; Herpes Simplex; Corneal Diseases

Condition Hierarchy (Ancestors)

Vision Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Skin Diseases, Viral; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Yujia Cai, PhD

  Shanghai BDgene Co., Ltd.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single group target value: Since there is no similar products approved on the market and there is no similar comparative treatment methods, the single group target value method is adopted

Study Record Dates

• First Submitted: September 17, 2020
• First Posted: September 23, 2020
• Study Start: November 4, 2020
• Primary Completion: July 5, 2022
• Study Completion: July 5, 2022
• Last Updated: August 24, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)