Study to Evaluate the Long-Term Efficacy and Safety of the Investigational Drug LIB003 for the Reduction of Cholesterol in Patients with Homozygous and Heterozygous Familial Hypercholesterolemia, Cardiovascular Disease, or at High Risk for Cardiovascular Disease.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Lib Therapeutics LLC

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

6 Oct 2021 → 19 Aug 2025

Decision date (initial)

2024-04-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

LIB Therapeutics, LLC

External identifiers

EU CT number

2023-510057-41-00

EudraCT number

2020-004394-49

WHO UTN

U1111-1303-2625

ClinicalTrials.gov

NCT04798430

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Efficacy, Safety, Therapy

The primary objectives of this study are to assess the long-term safety, tolerability, and efficacy after 48 and 72 weeks with monthly (Q4W [≤31 days]) dosing of LIB003 300 mg administered subcutaneously (SC). The study includes patients at very-high risk for CVD or at high risk for CVD (including HoFH and HeFH) on a stable diet and maximally tolerated oral LDL-C lowering drug therapy who completed a LIB003 Phase 3 base study.

Secondary objectives 1

1. There are not secondary objectives in this study.

Conditions and MedDRA coding

Patients With Homozygous and Heterozygous Familial Hypercholesterolemia, Cardiovascular Disease, or at High Risk for Cardiovascular Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Patient has received study drug through the end of study (EOS) with a complete EOS Visit in 1 of the Phase 3 base studies, LIB003-003, -004, - 005, -006, -008, -011 and -012, without SAEs related to LIB003;
2. 2. Patient has the provision of written and signed informed consent prior to any study-specific procedure;
3. 3. Female patients of childbearing potential must continue using a highly effective form of birth control if sexually active and have a negative urine pregnancy test on Day 1 prior to dosing; o Note: Highly effective methods of birth control include refraining from heterosexual sexual intercourse during the entire period of risk, birth control pills or patches, intrauterine devices (IUDs), sexual activity with a male partner who has had a vasectomy, IUD, oral, implantable, or injectable contraceptives. Menopause is defined as 1 year of spontaneous and continuous amenorrhea in a female ≥55 years old or 1 year of spontaneous and continuous amenorrhea with a folliclestimulating hormone (FSH) level >40 IU/L (or according to the definition of "postmenopausal range" for the laboratory involved) in a female <55 years old unless the patient has undergone bilateral oophorectomy. Birth control should be maintained for 60 days after the last dose of study drug (ie, 30 days after the last study visit). Postmenopausal women and those who are sterilised will be deemed of non-childbearing potential. All other women will be considered of childbearing potential and will be required to follow the contraception requirements as well as the pregnancy testing in the protocol. o Note: WOCBP will also have a pregnancy test prior to randomization, every 4 weeks for the duration of the study and at the final visit. Any participant who considers they or their partner is pregnant should undergo a pregnancy test until 60 days after last dose of study drug and if there is a positive test should follow the standard guidance for pregnancy in the clinical trial.
4. 4. Male patients will either be surgically sterile or agree to continue to use the following forms of contraception if their partner is of childbearing potential and not using a highly effective form of birth control as defined in Inclusion Criterion #3: male or female condom with spermicide and a female partner who is sterile or who agrees to use the following contraceptives; diaphragm or cervical cap with spermicide; or intrauterine device, oral, implantable, or injectable contraceptives;
5. 5. Male patients must refrain from sperm donation until 90 days following the last dose of study drug;
6. 6. Patient is willing to maintain appropriate diet and stable dose of current LLT, including statins, ezetimibe, bile acid sequestrants, niacin, lomitapide, bempedoic acid, bezafibrate or fenofibrate, and/or OM-3 compounds; and o Note: Use of lomitapide will be allowed in patients from LIB003-003. o Note: Use of bempedoic acid will be allowed in patients from LIB003- 004, -005, and -006. o Note: Patients still requiring apheresis may add the procedure after Week 12.
7. 7. Patient is considered by the Investigator to be otherwise healthy, based on medical history review, a defined complete physical examination, as well as vital sign measurements, ECGs, and laboratory test results in the base trial.

Exclusion criteria 6

1. 1. Failure to receive study drug through the EOS or to complete the EOS Visit in the Phase 3 base study (LIB003-003, -004, -005, -006, -008, - 011 or -012) and/or had an SAE that was related to study drug during the Phase 3 base study;
2. 2. Development since the final visit in the Phase 3 base study (LIB003- 003, -004, -005, -006, -008, -011 or -012) of any concomitant clinical condition or acute and/or unstable systemic disease compromising patient inclusion, at the discretion of the Investigator, including but not limited to, the following: a history or presence of clinically significant pulmonary, hepatic, gallbladder or biliary tract, hematologic, gastrointestinal, endocrine (excluding diabetes), immunologic, dermatologic, neurologic, or psychiatric disease, which in the Investigator's opinion would not be suitable for the study from a patient safety consideration or could interfere with the results of the study;
3. 3. Use of prohibited oral lipid-lowering agents, including PCSK9 mAbs, mipomersen, lomitapide, gemfibrozil, or bempedoic acid, started since completion of the base study; o Note: Use of lomitapide is not approved for, and will be prohibited in, patients from LIB003-004, -005, -006, -008, -011 and -012. o Note: Use of bempedoic acid is not approved for, and will be prohibited in, patients from LIB003-003, -008, -011 and -012.
4. 4. Not available for protocol-required study visits or procedures, to the best of the patient's and Investigator's knowledge;
5. 5. Has any other findings since the completion of the base study which, in the opinion of the Investigator, would compromise the patient's safety or participation in the study; or
6. 6. Is an employee or family member of the Investigator or study site personnel.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 10

1. 1. Efficacy. LDL-C change (absolute and percent) compared to original baseline LDL-C at Day 1 in the base study calculated by both Friedewald and Hopkins formulas and preparative ultracentrifugation at Weeks 48 and 72 for patients entering the OLE directly from studies LIB003-004, -005, -006, -008, -011 and -012;
2. 2. Efficacy. LDL-C change (absolute and percent) compared to original baseline LDL-C at Day 1 in the base study calculated by both Friedewald and Hopkins formulas and preparative ultracentrifugation at Weeks 48 and 72 for patients entering the OLE directly from study LIB003-003;
3. 3. Efficacy. LDL-C change (absolute and percent) compared to final LDL-C at the last visit of the base study calculated by both Friedewald and Hopkins formulas and preparative ultracentrifugation at Weeks 48 and 72 for only the base study placebo patients entering the OLE directly from studies LIB003-004, -005, -006, and -008;
4. 4. Efficacy. Effects of LIB003 at Weeks 48 and 72 on serum lipids, including TC, HDL-C, non–HDL-C, VLDL-C, and TG;
5. 5. Efficacy. Effects of LIB003 at Weeks 48 and 72 on apo B and Lp(a) serum concentrations. For patients entering from the LIB003-011 and -012 studies, effects on apo B and Lp(a) will also be assessed at Week 12 compared to Week 12 or Day 270 of the base studies, respectively;
6. 6. Efficacy. Effects of LIB003 at Weeks 48 and 72 on serum unbound (free) PCSK9 concentration; and
7. 7. Efficacy. The percentage of patients achieving current ESC/EAS guidelines.
8. 8. Immunogenicity. Anti-LIB003 antibodies will be initially measured at Week 72/Early Termination [ET]. Other visits including Weeks 12, 24, 36, 48, and 60 will be measured in response to ADAs at Week 72/ET or as indicated by the Data Safety Monitoring Board (DSMB).
9. 9. Pharmacokinetic. The PK concentration for LIB003 will be measured at Week 72/ET in support of ADAs. Other visits including Weeks 12, 24, 36, 48, and 60 will be measured in response to ADAs at Week 72/ET or as indicated by the DSMB.
10. 10. Safety. Safety endpoints are AEs, including CVEs and all-cause mortality; safety laboratory parameters, with particular attention to hepatic (eg, alanine transaminase [ALT]/aspartate transaminase [AST], bilirubin, alkaline phosphatase) and skeletal muscle (ie, creatine kinase [CK]) toxicities; 12-lead ECGs; ISRs; physical examinations; and vital signs.

Secondary endpoints 1

1. Not Applicable

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Lib Therapeutics LLC

Sponsor organisation

Lib Therapeutics LLC

Address

5375 Medpace Way

City

Cincinnati

Postcode

45227-1543

Country

United States

Scientific contact point

Organisation

Lib Therapeutics LLC

Contact name

Evan Stein

Public contact point

Organisation

Lib Therapeutics LLC

Contact name

Evan Stein

Third parties 2

Locations

4 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications