HypercholesterolemiaPhase 2NCT00231569
Dose-escalating Safety Study in Subjects on Stable Statin Therapy
A Phase 2 study of Hypercholesterolemia, run by Kastle Therapeutics, LLC at 5 sites in 2 countries.
Trial summary
The aim of this study is to assess the safety of varying doses of ISIS 301012 in subjects on Stable statin therapy. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hypercholesterolemia
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 74 participants
- Where
- 5 sitesin 2 countries
- Study dates
- Sep 2005to Dec 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- On a stable dose of >/= 40 mg Simvastatin or atorvastatin daily for >/= 3 months prior to baseline and expected to remain on this dose for the remainder of the study
- LDL-cholesterol between 2.60 and 5.70 mmol/L (100 and 220 mg/dL), inclusive at screening
- Females not of childbearing potential.
Who cannot join
- History of CHD or CHD-equivalent (such as diabetes mellitus, or another clinical form of atherosclerotic disease, e.g., peripheral arterial disease, abdominal aortic aneurysm, or symptomatic carotid artery disease)
- Fasting triglyceride >2.26 mmol/L (200 mg/dL) at screening
- Any uncontrolled medical/surgical/psychiatric condition, including conditions that may predispose to secondary hypercholesterolemia
- Current diagnosis or known history of complement deficiency or abnormality
- A positive hepatitis B surface antigen or hepatitis C antibody, or a known positive HIV status
- Current diagnosis or known history of liver disease, or has an ALT >ULN at screening
Show all 14Show fewer
- Known history of fibromyalgia, myopathy, myositis, rhabdomyolysis, any unexplained muscle pain, or has a CPK >ULN at screening
- Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin that has been adequately treated
- The advisability of a subject taking any prescription medication (apart from simvastatin or atorvastatin) within 6 weeks prior to screening should be discussed with the Isis Medical Monitor
- Subject unwilling to discontinue taking alternative/herbal medication for the duration of the study
- History of drug abuse within 2 years of screening
- Subject unwilling to limit alcohol consumption for the duration of the study: male subjects to a maximum of 3 drinks (30 g) per day, and <12 drinks (120 g) per week; female subjects to a maximum of 2 drinks (20 g) per day, and <8 drinks (80 g) per week
- Known allergy or hypersensitivity to simvastatin
- Undergoing or has undergone treatment with another investigational drug, biologic agent, or device within 3 months, or 3 half lives, prior to screening, whichever is longer
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
Netherlands4 sites
Study site
Amsterdam, 1105 AZ
Study site
Leiden, 2311 GZ
Study site
Rotterdam, 3021 HC
Study site
Utrecht, 3584 CX
About this study
Official title: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Assess the Safety and Pharmacodynamics of ISIS 301012 in Hypercholesterolemic Subjects on Stable Statin Therapy
The aim of this study is to assess the safety of varying doses of ISIS 301012 in subjects on Stable statin therapy.
- Conditions
- Hypercholesterolemia
- Being tested
- ISIS 301012 or Placebo
- Keywords
- LDL-cholesterol, apoB-100, apoB-48
- Medical subject headings
- Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ISIS 301012 or PlaceboDrug
30 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
ISIS 301012 or PlaceboDrug
100 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
ISIS 301012 or PlaceboDrug
200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
ISIS 301012 or PlaceboDrug
300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
ISIS 301012 or PlaceboDrug
400 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29
ISIS 301012 or PlaceboDrug
200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
ISIS 301012 or PlaceboDrug
300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Experimental | Loading doses followed by weekly maintenance doses Receives: Drug: ISIS 301012 or Placebo |
| Cohort B | Experimental | Loading doses followed by weekly maintenance doses Receives: Drug: ISIS 301012 or Placebo |
| Cohort C | Experimental | Loading doses followed by weekly maintenance doses Receives: Drug: ISIS 301012 or Placebo |
| Cohort D | Experimental | Loading doses followed by weekly maintenance doses Receives: Drug: ISIS 301012 or Placebo |
| Cohort E | Experimental | Loading doses followed by weekly maintenance doses Receives: Drug: ISIS 301012 or Placebo |
| Cohort F | Experimental | Loading doses followed by extended weekly maintenance doses Receives: Drug: ISIS 301012 or Placebo |
| Cohort G | Experimental | Loading doses followed by extended weekly maintenance doses Receives: Drug: ISIS 301012 or Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent reduction in LDL-cholesterol from baseline
Measured: From baseline measurement
Secondary outcomes (4)
Percent reduction in apoB-100
Measured: From baseline measurement
Percent change in HDL-cholesterol, triglycerides, total cholesterol, non-HDL cholesterol, VLDL plus LDL-cholesterol and LDL-cholesterol particle size and concentration
Measured: From baseline measurement
Percent change from baseline in LDL/HDL and apoB-100/apo-A1 ratios
Measured: From baseline measurement
AEs, SAEs, physical examination data, vital signs, and laboratory analyzes
Measured: Duration of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2005 (estimated)
- Study startSep 2005
- Primary completionJun 2007
- Study completionDec 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kastle Therapeutics, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ionis Pharmaceuticals, Inc.
- Investigators
- Medical Monitor, Study director, Genzyme, a Sanofi Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00231569
- Sponsor's protocol ID
- 301012CS4
- Other IDs
- EudraCT No.: 2005-002119-26
- Status last verified
- Dec 2013
- First submitted
- 3 Oct 2005
- Last updated
- 3 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Akdim F, Stroes ES, Sijbrands EJ, Tribble DL, Trip MD, Jukema JW, Flaim JD, Su J, Yu R, Baker BF, Wedel MK, Kastelein JJ. Efficacy and safety of mipomersen, an antisense inhibitor of apolipoprotein B, in hypercholesterolemic subjects receiving stable statin therapy. J Am Coll Cardiol. 2010 Apr 13;55(15):1611-8. doi: 10.1016/j.jacc.2009.11.069.
PubMed 20378080
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Assess the Safety and Pharmacodynamics of ISIS 301012 in Hypercholesterolemic Subjects on Stable Statin Therapy
- ClinicalTrials.gov ID
- NCT00231569
- Acronym / sponsor ID
- 301012CS4
- Conditions
- Hypercholesterolemia
- Keywords
- LDL-cholesterol, apoB-100, apoB-48
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Kastle Therapeutics, LLCIndustry (pharma, biotech, devices)
- Collaborators
- Ionis Pharmaceuticals, Inc.
- Study start
- Sep 2005
- Primary completion
- Jun 2007 (actual)
- Study completion
- Dec 2007 (actual)
- First posted
- 4 Oct 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to assess the safety of varying doses of ISIS 301012 in subjects on Stable statin therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Cohort A | Experimental | Drug: ISIS 301012 or PlaceboLoading doses followed by weekly maintenance doses |
| Cohort B | Experimental | Drug: ISIS 301012 or PlaceboLoading doses followed by weekly maintenance doses |
| Cohort C | Experimental | Drug: ISIS 301012 or PlaceboLoading doses followed by weekly maintenance doses |
| Cohort D | Experimental | Drug: ISIS 301012 or PlaceboLoading doses followed by weekly maintenance doses |
| Cohort E | Experimental | Drug: ISIS 301012 or PlaceboLoading doses followed by weekly maintenance doses |
| Cohort F | Experimental | Drug: ISIS 301012 or PlaceboLoading doses followed by extended weekly maintenance doses |
| Cohort G | Experimental | Drug: ISIS 301012 or PlaceboLoading doses followed by extended weekly maintenance doses |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- On a stable dose of >/= 40 mg Simvastatin or atorvastatin daily for >/= 3 months prior to baseline and expected to remain on this dose for the remainder of the study
- LDL-cholesterol between 2.60 and 5.70 mmol/L (100 and 220 mg/dL), inclusive at screening
- Females not of childbearing potential.
Key exclusion criteria (14 listed)
- History of CHD or CHD-equivalent (such as diabetes mellitus, or another clinical form of atherosclerotic disease, e.g., peripheral arterial disease, abdominal aortic aneurysm, or symptomatic carotid artery disease)
- Fasting triglyceride >2.26 mmol/L (200 mg/dL) at screening
- Any uncontrolled medical/surgical/psychiatric condition, including conditions that may predispose to secondary hypercholesterolemia
- Current diagnosis or known history of complement deficiency or abnormality
- A positive hepatitis B surface antigen or hepatitis C antibody, or a known positive HIV status
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ISIS 301012 or Placebo30 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29 | Drug | Cohort A |
| ISIS 301012 or Placebo100 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29 | Drug | Cohort B |
| ISIS 301012 or Placebo200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29 | Drug | Cohort C |
| ISIS 301012 or Placebo300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29 | Drug | Cohort D |
| ISIS 301012 or Placebo400 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, and 29 | Drug | Cohort E |
| ISIS 301012 or Placebo200 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85 | Drug | Cohort F |
| ISIS 301012 or Placebo300 mg subcutaneous injection on days 1, 8, 10, 12, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85 | Drug | Cohort G |
Primary outcome
Percent reduction in LDL-cholesterol from baseline
Time frame: From baseline measurement
4 secondary outcomes
Percent reduction in apoB-100
Time frame: From baseline measurement
Percent change in HDL-cholesterol, triglycerides, total cholesterol, non-HDL cholesterol, VLDL plus LDL-cholesterol and LDL-cholesterol particle size and concentration
Time frame: From baseline measurement
Percent change from baseline in LDL/HDL and apoB-100/apo-A1 ratios
Time frame: From baseline measurement
AEs, SAEs, physical examination data, vital signs, and laboratory analyzes
Time frame: Duration of study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2016.
- Derived from this study: PubMed 20378080Akdim F, Stroes ES, Sijbrands EJ, Tribble DL, Trip MD, Jukema JW, Flaim JD, Su J, Yu R, Baker BF, Wedel MK, Kastelein JJ. Efficacy and safety of mipomersen, an antisense inhibitor of apolipoprotein B, in hypercholesterolemic subjects receiving stable statin therapy. J Am Coll Cardiol. 2010 Apr 13;55(15):1611-8. doi: 10.1016/j.jacc.2009.11.069.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Genzyme, a Sanofi Company
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study of Hypercholesterolemia, run by Kastle Therapeutics, LLC at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Netherlands, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent reduction in LDL-cholesterol from baseline (time frame: From baseline measurement). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00231569, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2016.