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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12623000809639
Ethics application status
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Approved
Date submitted
Help: Date submitted
21/06/2023
Date registered
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27/07/2023
Date last updated
Help: Date last updated
26/08/2026
Date data sharing statement initially provided
Help: Data sharing statement date
27/07/2023
Type of registration
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Prospectively registered

Titles & IDs
Public title
A Safety and Tolerability Study Evaluating CTX310 in Participants With Refractory Dyslipidemias
Scientific title
A Phase 1 Open-label, Multicenter, First-in-human, Ascending Dose Trial Evaluating the Safety and Tolerability of a Lipid Nanoparticle Formulation of CRISPR–Guide RNA–Cas9 Nuclease (CTX310) for In Vivo Editing of the Angiopoietin-like 3 (ANGPTL3) Gene in Participants With Refractory Dyslipidemias
Additional trial identifiers [1] 309491 0
NCT07491172
Universal Trial Number (UTN)
Trial acronym
Related trial records

Health condition
Health condition(s) studied:
Refractory Dyslipidemias 329760 0
Severe Hypertriglyceridemia (sHTG) 343389 0
Heterozygous Familial Hypercholesterolemia (HeFH) 343390 0
Homozygous Familial Hypercholesterolemia (HoFH) 343391 0
Mixed Hyperlipemia 343392 0
Condition category
Condition code
Cardiovascular 326658 326658 0 0
Other cardiovascular diseases
Metabolic and Endocrine 327353 327353 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
This is a single-arm, open-label, multicenter, ascending single-dose Phase 1 study. Subjects will receive a single dose of CTX310 via intravenous (IV) infusion. Planned ascending dose levels will be 0.1 mg/kg, 0.3 mg/kg, 0.6 mg/kg, 0.8 mg/kg. Participants will receive only one dose in each phase. The study will consist of 2 Phases: Phase 1a and Phase 1b. Phase 1a (15 participants) will be the dose escalation portion and Phase 1b (up to 69 participants) will consist of four disease-specific cohort expansions.
Intervention code [1] 325919 0
Treatment: Drugs
Description of the comparator or control
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 334527 0
Incidence of dose-limiting toxicities (DLTs) and frequency of Adverse Events (AEs). Potential adverse reactions include infusion related reactions and abnormal liver changes. 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. back pain, flushing, 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 [1] 334527 0
AEs and DLTs will be monitored for up to 12 months 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. Assessment methods used to assess AEs and DLTs will include vital signs, nurse assessments (Heart rate and oxygen saturation monitored with finger pulse oximeter, blood pressure assessed with blood pressure cuff), clinical observation, blood and urine tests, 12 lead ECG and physical examinations.
Secondary outcome [1] 421025 0
Frequency and severity of AEs, including treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), clinically significant laboratory abnormalities and clinically significant abnormal vital signs. Potential adverse reactions include infusion related reactions and abnormal liver changes. 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. back pain, flushing, 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 [1] 421025 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. Assessment methods used to assess AEs TEAEs and AESIs will include vital signs, nurse assessments (Heart rate and oxygen saturation monitored with finger pulse oximeter, blood pressure assessed with blood pressure cuff), clinical observation, blood and urine tests, 12 lead ECG and physical examinations.
Secondary outcome [2] 421026 0
Pharmacokinetic exposure to CTX310 over time. Plasma samples will be collected at Screening, D1 (prior to infusion, within 5 minutes post-CTX310 infusion, and at 1, 2, and 7 hours after completion of CTX310 infusion), D2, D3, D4, D7, D14, D30, M3, M6, M12 to assess the LNP lipid levels and Cas9 protein via LC- MS/MS and ELISA, respectively. Plasma levels over time will be summarized using descriptive statistics. Exploratory analysis based on an applicable PK model may be performed.
Timepoint [2] 421026 0
Screening, Day 1 (prior to infusion, within 5 minutes post-CTX310 infusion, and at 1, 2, and 7 hours after completion of CTX310 infusion), Days 2, 3, 4, 7, 14, 30 and Months 3, 6, and 12 post-intervention dose.
Secondary outcome [3] 424042 0
Percentage change in ANGPTL3 concentration over time compared to baseline. Plasma ANGPTL3 levels will be assessed via ELISA. Samples will be collected at Screening, D14, D30, M3, M6, M9 and M12. Percentage change in ANGPTL3 concentration over time compared to baseline will be summarized using descriptive statistics.
Timepoint [3] 424042 0
Screening, Days 14, 30, and Months 3, 6, 9 and 12 post-intervention dose.
Secondary outcome [4] 424043 0
Percentage change in triglycerides (TG) over time compared to baseline. Blood tests will be used to assess percent change.
Timepoint [4] 424043 0
Screening, Days 14 and 30, and Months 2, 3, 6, 9 and 12 post-intervention dose.

Eligibility
Key inclusion criteria
1. Age of greater than or equal to 18 and less than or equal to 75 years at the time of signing the informed consent.
2. Able to provide written informed consent.
3. Participants diagnosed with persistent dyslipidemias defined by TG greater than or equal to 150 mg/dL - and LDL-C greater than or equal to 70 mg/dL in participants with ASCVD, or LDL-C greater than or equal to 70 or 100mg/dL in participants with or without ASCVD respectively, or TG greater than or equal to 500 mg/dL.
4. Refractory to the maximal intensity or MTD of standard of care lines of lipid-lowering therapies available through routine clinical care, for at least 12 weeks prior to screening
5. Female participants must be postmenopausal or surgically sterile.
6. All male participants and their female partners must agree to the use of an acceptable method of effective contraception for the duration of the study.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
1. Participants with familial chylomicronemia syndrome (FCS). Some exceptions may apply.
2. Evidence of liver disease, defined as but not limited to:
LFTS greater than 2 times upper limit of normal (ULN), or total bilirubin greater than 2 times ULN, or INR greater than 1.5 times ULN, or liver stiffness measured by liver elastography
3. Abnormal or compromised function of kidney, heart, blood or liver.
4. Acute coronary syndrome event or stroke within 24 weeks prior to Day 1. Acute pancreatitis within 12 weeks prior to Day 1.
5. Current use or use within 365 days from Day 1 of any hepatocyte-targeted small interfering RNA (except inclisiran).
6. Positive serology for HIV, hepatitis B or hepatitis C (antibody, surface antigen or NAT). Serology consistent with prior immunization will be eligible for the trial.
7. Any prior malignancy within the past 5 years, or current malignancy (exceptions for resected or removed basal cell carcinoma, squamous cell carcinoma in situ and carcinoma in situ of the cervix or breast).
8. Women of childbearing potential.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Note: The inclusion and exclusion criteria listed represent the global protocol. Additional or modified eligibility criteria may apply in certain countries in accordance with local regulatory and ethics committee requirements and the approved country-specific protocol.

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
Recruiting
Date of first participant enrolment
Anticipated
15/09/2023
Actual
21/06/2024
Date of last participant enrolment
Anticipated
30/06/2027
Actual
Date of last data collection
Anticipated
30/06/2028
Actual
Sample size
Target
69
Accrual to date
15
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 26481 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [2] 30076 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 30077 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 42471 0
3168 - Clayton
Recruitment postcode(s) [2] 46471 0
5000 - Adelaide
Recruitment postcode(s) [3] 46472 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 28472 0
New Zealand
State/province [1] 28472 0
Auckland
Country [2] 28473 0
United Kingdom
State/province [2] 28473 0
England

Funding & Sponsors
Funding source category [1] 313688 0
Commercial sector/Industry
Name [1] 313688 0
CRISPR Therapeutics AG
Country [1] 313688 0
Switzerland
Primary sponsor type
Commercial sector/Industry
Name
CRISPR Therapeutics AG
Address
Baarerstrasse 14
ZUG V8 CH-6300
Country
Switzerland
Secondary sponsor category [1] 315488 0
Commercial sector/Industry
Name [1] 315488 0
MedPace
Address [1] 315488 0
5355 Medpace Way, Cincinnati, OH, 45227
Country [1] 315488 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312846 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 312846 0
Ethics committee country [1] 312846 0
Australia
Date submitted for ethics approval [1] 312846 0
Approval date [1] 312846 0
29/09/2023
Ethics approval number [1] 312846 0
Ethics committee name [2] 321271 0
Northern B Health and Disability Ethics Committee 
Ethics committee address [2] 321271 0
Ethics committee country [2] 321271 0
New Zealand
Date submitted for ethics approval [2] 321271 0
30/08/2023
Approval date [2] 321271 0
13/12/2023
Ethics approval number [2] 321271 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 126126 0
Prof Stephen Nicholls
Address 126126 0
Program Director | Victorian Heart Hospital and Intensive Care Director | Victorian Heart Institute Director | Velos Research Accelerator 631 Blackburn Rd, Clayton VIC 3168 
Country 126126 0
Australia
Phone 126126 0
+61 395942726
Fax 126126 0
Email 126126 0
[email protected]
Contact person for public queries
Name 126127 0
Medical Affairs
Address 126127 0
CRISPR Therapeutics 105 W. First St, Boston, MA 02127
Country 126127 0
United States of America
Phone 126127 0
+1 8772144634
Fax 126127 0
Email 126127 0
[email protected]
Contact person for scientific queries
Name 126128 0
Dr. Jason Duran
Address 126128 0
Clinical Development, 105 W. First St, Boston, MA 02127
Country 126128 0
United States of America
Phone 126128 0
+1 8772144634
Fax 126128 0
Email 126128 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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.