Primary: To collect long-term safety data.Secondary objectives: To collect long-term efficacy data (LDL-C).
ID
Source
Brief title
Condition
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Adverse events.
Secondary outcome
LDL-C at week 48 and 104.
Background summary
AMG 145 is a fully human monoclonal immunoglobulin (Ig) G2 that binds
specifically to human proprotein convertase subtilisin/kexin type 9 (PCSK9) and
prevents the interaction of PCSK9 with the LDL receptor. AMG 145 caused a
dose-related inhibition of PCSK9 binding to the LDL receptor and of the
PCSK9-mediated reduction in low-density lipoprotein (LDL) uptake in hepatic
cells. Treatment of cells with a combination of AMG 145 and statin increased
LDL receptor protein levels more than treatment with either alone. Single
administrations in humans produced decreases in mean LDL-C with subsequent
returns to baseline. Across the dose groups, the decreases were dose-related.
Overall, AMG 145 appeared to be well tolerated at the IV and SC doses
administered in this FIH study. Incidences of overall adverse events and
treatment-related adverse events did not differ notably between treatment
groups.
De current study is an extension of 3 studies with AMG 145 that are currently
being executed in the Netherlands:
1. A Double-blind, Randomized, Placebo and Ezetimibe Controlled, Multicenter
Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 on LDL-C in
Combination With Statin Therapy in Subjects With Primary Hypercholesterolemia
and Mixed Dyslipidemia (AMG 145 20110115)
EudraCT number: 2012-001363-70, CCMO number NL40964.018.12.
2. A Double-blind, Randomized, Multicenter Study to Evaluate Safety and
Efficacy of AMG 145, Compared With Ezetimibe, in Hypercholesterolemic Subjects
Unable to Tolerate an Effective Dose of a HMG-CoA Reductase Inhibitor (AMG 145
20110116)
EudraCT number: 2012-001364-30, CCMO number NL40965.018.12
3. A Double-blind, Randomized, Placebo-controlled, Multicenter Study to
Evaluate Safety, Tolerability and Efficacy of AMG 145 on LDL-C in Subjects with
Heterozygous Familial Hypercholesterolemia (AMG 145 20110117)
EudraCT number: 2012-001365-32, CCMO number NL40966.018.12
4. A Double-blind, Randomized, Multicenter Study to Evaluate the
Safety and Efficacy of AMG 145, Compared With Ezetimibe, in
Hypercholesterolemic Subjects Unable to Tolerate an Effective Dose of a HMG-CoA
Reductase Inhibitor Due to Muscle Related Side Effects
EudraCT nummer: 2013-000935-29, CCMO nummer NL46854.018.14 (AMG145 20120332
GAUSS-3, this study only takes place at sites AMC and SFG)
Subjects who have completed one of the parent studies and do not discontinue IP
in the parent study for any reason including an adverse event will be eligible
for this extension study. The GAUSS-3 study is a study for statin intolerant
patients and consists of 3 parts. In part A subjects will be actively
rechallenged on statin therapy. Only subjust that have a proven statin
intolerance in aprt A will continue into part B (AMG145 vs ezetimibe) and part
C (open label AMG 145). it is expected that 20% of the subjects in part A will
continue into part B/C. Subject that cannot continue into part B of the study
can roll-over into teh OSLER-2 study.
The main objective of the extension study is to collect long-term safety data.
Study objective
Primary: To collect long-term safety data.
Secondary objectives: To collect long-term efficacy data (LDL-C).
Study design
Multicenter randomized open-label phase III extension study.
Randomization (2:1) within 30 days after the end of the parent study to:
* AMG 145 plus standard of care
* Standard of care.
Patient may choose between injections AMG 145 every 2 weeks (140 mg s.c.) or
every month (420 mg s.c.). AMG 145 injections will be administered by the
patient via the auto innjector pen or 3.5 ml personal injector (if available)
During the first 12 weeks LDL-C will remain blinded (investigator will be
informed if triglycerides are > 11.3 mmol/L) and subjects must remain on stable
background lipid lowering therapy. Background lipid lowering therapy: therapy
either prescribed to the subject prior to participation in parent study or
statin or ezetimibe therapy given during parent study.
After week 48 all subjects will receive open-label AMG 145 for approximately 2
year.
Approx. 4500 patients.
Intervention
Treatment with AMG 145.
Study burden and risks
Risk: Adverse effects of study medication.
Burden: Study duration approx. 2 years. Visits every 12 weeks.
Every month collection of injection(s) to be self-adminsitered and discussion
of any signs or symptoms.
Two additional visits for training of self-injection for those patients not yet
familiar with self-injection.
Additional full visit in week 60 for those who have received AMG 145 after the
first 48 weeks for the first time ever.
AMG 145 s.c.: 1 injection (1 mL) every 2 weeks or 3 injections (1 mL) every
month during 104 or 56 weeks via the auto injector of 3.5 ml personal injector
(if available)
Physical examination 2x.
Blood tests 7x (fasting), 30-60 ml/occasion.
Urine tests 6x.
Minervum 7061
Breda 4817 ZK
NL
Minervum 7061
Breda 4817 ZK
NL
Listed location countries
Age
Inclusion criteria
Subjects will be eligible for the study if they complete a qualifying AMG 145 parent study protocol while still on assigned study medication.
Exclusion criteria
Subjects will be ineligible for the study if they fulfill any of the following criteria:
1. Discontinued assigned study drug during the qualifying study for any reason
including an adverse event or serious adverse event.
2. Female subject is not willing to use an acceptable method(s) of effective birth
control during treatment with investigational product (IP) and for an additional
15 weeks after the end of treatment with IP. Female subjects, who have had a
hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or who are
postmenopausal, are not required to use contraception
o Menopause is defined as 12 months of spontaneous and continuous
amenorrhea in a female * 55 years old; or age < 55 years but no
spontaneous menses for at least 2 years; or age < 55 years and
spontaneous menses within the past 1 year, but currently
amenorrheic (eg, spontaneous or secondary to hysterectomy), and
with postmenopausal gonadotropin levels (luteinizing hormone and
follicle stimulating hormone levels > 40 IU/L) or postmenopausal
estradiol levels (<5 ng/dL) or according to the definition of
"postmenopausal range" for the laboratory involved.
o Acceptable methods of effective contraception are defined in the
ICF. Where required by local laws, regulations and/or guidelines,
additional country-specific requirements are outlined in a
country-specific protocol supplement.
3. Female subject is pregnant or breast feeding, planning to become pregnant or
planning to breastfeed during treatment with IP and/or within 15 weeks after
the end of treatment with IP.
4. Unreliability as a study participant based on the investigator's (or designee*s)
knowledge of the subject (eg, inability or unwillingness to adhere to the protocol).
5. Disorder that would interfere with understanding and giving informed consent or
compliance with protocol requirements.
6. Have an unstable medical condition, in the judgment of the investigator.
7. Subject*s medical condition requires lipid measurement and/or adjustment of
background lipid-regulating therapy during the first 12 weeks of study
participation.
8. Known sensitivity to any of the products to be administered during dosing.
9. Currently enrolled in another investigational device or drug study (excluding
AMG 145 parent study), or less than 30 days since ending another
investigational device or drug study(s),or receiving other investigational agent(s).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clinical trials.gov; registratienummer n.n.b. |
| EudraCT | EUCTR2012-004357-83-NL |
| CCMO | NL44053.060.13 |