Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001095651p
Ethics application status
Submitted, not yet approved
Date submitted
21/09/2023
Date registered
18/10/2023
Date last updated
18/10/2023
Date data sharing statement initially provided
18/10/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Safety and Tolerability Study Evaluating CTX320 in Subjects With Elevated Lipoprotein(a) and a History of Atherosclerotic Cardiovascular Disease or Calcific Aortic Valve Stenosis.
Scientific title
A Phase 1 Open-label, Multicenter, First-in-human, Ascending Single Dose Study Evaluating the Safety and Tolerability of a Lipid Nanoparticle Formulation of CRISPR–Guide RNA–Cas9 Nuclease (CTX320) for In Vivo Editing of the Apolipoprotein(a) Gene (LPA) in Subjects with Elevated Lipoprotein(a) and a History of Atherosclerotic Cardiovascular Disease or Calcific Aortic Valve Stenosis
Secondary ID [1] 310509 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Elevated Lipoprotein(a) 331312 0
Calcific Aortic Valve Stenosis 331313 0
Atherosclerotic Cardiovascular Disease 331795 0
Condition category
Condition code
Cardiovascular 328069 328069 0 0
Other cardiovascular diseases
Metabolic and Endocrine 328070 328070 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single-arm, open-label, multicenter, ascending single-dose Phase 1 study. Subjects will receive a single dose of CTX320 via intravenous (IV) infusion. The duration of the infusion is expected to take 1 hour. Planned ascending doses levels will range from 0.1 mg/kg - 0.8 mg/kg. Participants will receive only one dose.
Intervention code [1] 326903 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 335937 0
Incidence of dose-limiting toxicities (DLTs). DLTs will be monitored with blood and urine tests, physical exam, vital sign assessments and 12 lead ECG. DLTs will be graded using CTCAE version 5.0.
Timepoint [1] 335937 0
DLTs will be closely monitored post-infusion during the 30-day acute safety evaluation period and for up to 12 months post-intervention dose.
Secondary outcome [1] 426194 0
Percentage change in apo B concentrations over time compared to baseline. Blood tests will be used to assess percent change.
Timepoint [1] 426194 0
Screening, Days 14 and 30, Months 2, 3, 6, 9, and 12 post-intervention dose.
Secondary outcome [2] 426195 0
Frequency and severity of adverse events (AEs) including, treatment-emergent adverse events (TEAEs) and adverse event of special interests (AESIs), clinically significant laboratory abnormalities, and clinically significant abnormal vital signs. This is a first in human study and there is limited data about possible AEs. Based on non-clinical assessments and clinical experience with similar products, potential AEs include infusion related reactions (IRR) and transient elevations in liver transaminases. IRR will be evaluated with vital signs and nurse assessments (Heart rate and oxygen saturation monitored with finger pulse oximeter, blood pressure assessed with blood pressure cuff. Respiratory rate and monitoring for signs of infusion reaction (e.g. coughing, rash) will be evaluated with clinical observation. Liver function will be monitored with blood tests (ALP, ALT, AST, bilirubin, PT, PTT). Monitoring for other unanticipated adverse events will be performed with 12 lead ECG, blood and urine tests and physical examination.
Timepoint [2] 426195 0
AEs, TEAEs, and AESIs will be monitored for up to 12 months post-intervention dose. Clinical observations and vital signs will be monitored at Screening, daily for the first 4 days following infusion, Weeks 1, 2, and 3, and Months 1, 2, 3, 6, 9 and 12 post-intervention dose. Laboratory assessments will be monitored at Screening, daily for the first 4 days following infusion, Weeks 1, 2, and 3, and Months 1, 3, 6, 9 and 12 post-intervention dose.
Secondary outcome [3] 426196 0
Pharmacokinetics of CTX320 over time. Plasma samples will be collected at Screening, D1 (prior to infusion, within 5 minutes post-CTX320 infusion, and at 1, 2, and 7 hours after completion of CTX320 infusion), D2, D3, D4, D7, D14, D30, M3, M6, M12 to assess the levels of LNP lipids and Cas9 protein via LC-MS/MS and ELISA, respectively.
Timepoint [3] 426196 0
Screening, Day 1 (prior to infusion, within 5 minutes post-CTX320 infusion, and at 1, 2, and 7 hours after completion of CTX320 infusion), Days 2, 3, and 4, Weeks 1 and 2, and Months 1, 3, 6, and 12 post-intervention dose.
Secondary outcome [4] 426256 0
Percentage change in Lipoprotein (a) [Lp(a)] concentrations over time compared to baseline. Blood tests will be used to assess percent change.
Timepoint [4] 426256 0
Screening, Days 14 and 30, Months 2, 3, 6, 9, and 12 post-intervention dose.

Eligibility
Key inclusion criteria
1. Subjects diagnosed with a history of stable atherosclerotic cardiovascular disease or presence of mild to moderate calcific aortic valve disease
2. Subjects on available standard of care lines of treatment
3. Elevated serum Lp(a)
4. All subjects and their partners should agree to use an effective method of contraception through at least 12 months after CTX320 infusion
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Evidence of liver disease
2. History of alcohol or drug abuse
3. History of a significant coagulation disorder
4. Severe aortic stenosis
5. Uncontrolled or untreated thyroid disease
6. Prior treatment with gene therapy/editing product
7. Active HIV, hepatitis B virus or hepatitis C virus infection
8. Any prior or current malignancy or myeloproliferative disorder or a significant immunodeficiency disorder
9. Women who are pregnant or breastfeeding

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/01/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,WA
Recruitment outside Australia
Country [1] 25749 0
New Zealand
State/province [1] 25749 0

Funding & Sponsors
Funding source category [1] 314713 0
Commercial sector/Industry
Name [1] 314713 0
CRISPR Therapeutics AG
Country [1] 314713 0
Switzerland
Primary sponsor type
Commercial sector/Industry
Name
CRISPR Therapeutics AG
Address
Baarerstrasse 14ZUG V8 CH-6300
Country
Switzerland
Secondary sponsor category [1] 316682 0
Commercial sector/Industry
Name [1] 316682 0
MedPace
Address [1] 316682 0
5355 Medpace Way, Cincinnati, OH, 45227
Country [1] 316682 0
United States of America

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 313722 0
Bellberry HREC
Ethics committee address [1] 313722 0
123 Glen Osmond RoadEastwood SA 5063
Ethics committee country [1] 313722 0
Australia
Date submitted for ethics approval [1] 313722 0
13/10/2023
Approval date [1] 313722 0
Ethics approval number [1] 313722 0

Summary
Brief summary
This study aims to evaluate the safety and tolerability of a single ascending dose of CTX320 in patients with elevated lipoprotein(a) and a history of atherosclerotic cardiovascular disease or calcific aortic valve stenosis and to determine the recommended Phase 2 dose.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 129142 0
A/Prof David Sullivan
Address 129142 0
Head of Dept Chemical Pathology, Royal Prince Alfred Hospital, Sydney Local Health District and NSW Health Pathology. Missenden Rd Camperdown NSW 2050 Australia
Country 129142 0
Australia
Phone 129142 0
+61 295158832
Fax 129142 0
Email 129142 0
David.Sullivan1@health.nsw.gov.au
Contact person for public queries
Name 129143 0
Dr Sandeep Soni
Address 129143 0
CRISPR Therapeutics AG, Clinical Development, 105 W. First St, Boston, MA 02127
Country 129143 0
United States of America
Phone 129143 0
+1 8772144634
Fax 129143 0
Email 129143 0
sandeep.soni@crisprtx.com
Contact person for scientific queries
Name 129144 0
Dr Sandeep Soni
Address 129144 0
CRISPR Therapeutics AG, Clinical Development, 105 W. First St, Boston, MA 02127
Country 129144 0
United States of America
Phone 129144 0
+1 8772144634
Fax 129144 0
Email 129144 0
sandeep.soni@crisprtx.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.