Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ended
Participants planned
442
Countries
3
Sites
18
Mixed Dyslipidemia
To evaluate the safety and efficacy of long-term treatment with ARO-APOC3 in adults with mixed dyslipidemia.
Key facts
- Sponsor
- Arrowhead Pharmaceuticals Inc.
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Trial duration
- 4 Jul 2024 → 2 Dec 2025
- Decision date (initial)
- 2024-07-04
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Arrowhead Pharmaceuticals, Inc.
External identifiers
- EU CT number
- 2024-511331-96-00
- EudraCT number
- 2022-001135-85
- ClinicalTrials.gov
- NCT05413135
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy
To evaluate the safety and efficacy of long-term treatment with ARO-APOC3 in adults with mixed dyslipidemia.
Conditions and MedDRA coding
Mixed Dyslipidemia
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 26.0 | LLT | 10027763 | Mixed hyperlipidemia | 10010331 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Single arm open label extension of the parent studies AROAPOC3-2001 and AROAPOC3-2002 Eligible enrolled participants will initially receive open-label ARO-APOC3 at the assigned dose level until a final dose is selected from the parent studies, at which point all participants will be transitioned to the selected dosing regimen.
|
Not Applicable | None |
Regulatory references
- Scientific advice from competent authorities
- Food And Drug Administration, European Medicines Agency
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2021-000687-30 | A Double-Blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of ARO-APOC3 in Adults with Severe Hypertriglyceridemia, Kettős vak, placebo kontrollált IIb. fázisú vizsgálat az ARO-APOC3 készítmény hatásosságának és biztonságosságának értékelésére, súlyos hipertrigliceridémiában szenvedő felnőttek esetében | |
| 2021-000688-57 | A Double-blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of ARO-APOC3 in Adults with Mixed Dyslipidemia, Kettős vak, placebo kontrollált IIb. fázisú vizsgálat az ARO APOC3 hatásosságának és biztonságosságának értékelésére kevert diszlipidémiában szenvedő felnőttek esetében, Kettős vak, placebo kontrollált IIb. fázisú vizsgálat az ARO APOC3 hatásosságának és biztonságosságának értékelésére kevert diszlipidémiában szenvedő felnőttek esetében, Prowadzone metodą podwójnie ślepej próby z grupą kontrolną otrzymującą placebo, badanie fazy IIb mające na celu ocenę skuteczności i bezpieczeństwa stosowania ARO-APOC3 u osób dorosłych z dyslipidemią mieszaną, Prowadzone metodą podwójnie ślepej próby z grupą kontrolną otrzymującą placebo, badanie fazy IIb mające na celu ocenę skuteczności i bezpieczeństwa stosowania ARO-APOC3 u osób dorosłych z dyslipidemią mieszaną, Prowadzone metodą podwójnie ślepej próby z grupą kontrolną otrzymującą placebo, badanie fazy IIb mające na celu ocenę skuteczności i bezpieczeństwa stosowania ARO-APOC3 u osób dorosłych z dyslipidemią mieszaną, Prowadzone metodą podwójnie ślepej próby z grupą kontrolną otrzymującą placebo, badanie fazy IIb mające na celu ocenę skuteczności i bezpieczeństwa stosowania ARO-APOC3 u osób dorosłych z dyslipidemią mieszaną |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Adults ≥18 years of age who are nonpregnant, nonlactating, and do not plan to become pregnant during the study
- Able and willing to provide written informed consent prior to the performance of any study specific procedures
- Completed the 48-week study treatment period in the parent study
Exclusion criteria 3
- Subject was permanently discontinued from ARO-APOC3 in the parent study due to: a. Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT), or b. Elevated HbA1c. (hemoglobin A1c).
- Any new condition or worsening of existing condition (eg, renal, hematologic, gastrointestinal, endocrine, cardiovascular, pulmonary, immunologic, psychiatric) or any other situation that, in the Investigator’s judgment, would make the subject unsuitable for enrollment, could interfere with the subject participating in or completing the study, would make it difficult to comply with protocol requirements, or put the subject at additional safety risk
- Unwilling to limit alcohol consumption to within moderate limits for the duration of the study, as follows: not more than 14 units per week (1 unit approximately corresponds to 80 mL of wine, 200 mL of beer, or 25 mL of 40% alcohol)
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Subject incidence of treatment-emergent adverse events (TEAEs)
Secondary endpoints 6
- Change and percent change from baseline over time in fasting TG (triglyceride)
- Change and percent change from baseline over time in apolipoprotein (Apo)C-III
- Change and percent change from baseline over time in fasting non-high-density lipoprotein cholesterol (non-HDL-C)
- Change and percent change from baseline over time in fasting HDL-C
- Change and percent change from baseline over time in fasting total apolipoprotein B (ApoB)
- Change and percent change from baseline over time in fasting LDL-C (low-density lipoprotein cholesterol) using ultracentrifugation
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD9077320 · Product
- Active substance
- Synthetic Double-Stranded Sirna Oligonucleotide Directed Against Apolipoprotein C-Iii Mrna and Covalently Linked to a Ligand Containing Three N-Acetylgalactosamine Residues
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 200 mg milligram(s)
- Max treatment duration
- 104 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- ARROWHEAD PHARMACEUTICALS INC.
- Paediatric formulation
- No
- Orphan designation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Arrowhead Pharmaceuticals Inc.
- Sponsor organisation
- Arrowhead Pharmaceuticals Inc.
- Address
- 177 East Colorado Boulevard Suite 700
- City
- Pasadena
- Postcode
- 91105-1976
- Country
- United States
Scientific contact point
- Organisation
- Arrowhead Pharmaceuticals Inc.
- Contact name
- Armine Balian
Public contact point
- Organisation
- Arrowhead Pharmaceuticals Inc.
- Contact name
- Armine Balian
Third parties 8
| Organisation | City, country | Duties |
|---|---|---|
| Cenduit LLC - IWRS ORL-000003747
|
Allentown, PA, United States | Other |
| Fortrea Inc. ORG-100012602
|
Durham, United States | Code 8 |
| Opt-X-Pense Kft. ORG-100047138
|
Budaors, Hungary | Other |
| Kaleidoscope Data Privacy Consultants Limited ORG-100050361
|
Dublin 7, Ireland | Other |
| MEDPACE LABORATORIES ORG-100042942
|
Leuven, Belgium | Laboratory analysis |
| Iqvia Biotech Limited ORG-100008726
|
Reading, United Kingdom | On site monitoring, Code 11, Code 12, Code 13, Code 2, Interactive response technologies (IRT), Code 5, Code 8 |
| Pharmalex UK Services Limited ORG-100009244
|
Tring, United Kingdom | Other |
| Charles River Laboratories Montreal ULC ORG-100041009
|
Senneville, Canada | Other |
Locations
3 EU/EEA countries · 18 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Hungary | Ended | 140 | 8 |
| Netherlands | Ended | 7 | 3 |
| Poland | Ended | 31 | 7 |
| Rest of world
Canada, New Zealand, United States, Australia
|
— | 264 | — |
Investigational sites
Lausmed Kft.
Private Cardiology, Fulep Lajos Utca 15, 6500, Baja
DRC Kft.
Private Cardiology, Ady Endre Utca 12/b, 8230, Balatonfured
Borbanya Praxis Egeszsegugyi Kft.
Private Cardiology, Bazsalikom Utca 1/1, Borbanya, Nyiregyhaza
University Of Debrecen
Cardiology Department, Nagyerdei Korut 98, 4032, Debrecen
Pharma 4 Trial Kft.
Cardiology, Torok Ignac Utca 17, 3200, Gyongyos
Belgyogyaszati - Kardiologiai Maganrendelo
Private Cardiology, Also Koros Sor 21, 5600, Bekescsaba
Medifarma-98 Kft.
Private Cardiology, Praga Utca 9, 4400, Nyiregyhaza
Komaromi Selye Janos Korhaz
Cardiology, Szechenyi Utca 2, Szony, Komarom
Albert Schweitzer Ziekenhuis
Internal medicine, Albert Schweitzerplaats 25, 3318 AT, Dordrecht
Amsterdam UMC Stichting
Vascular Medicine, Meibergdreef 9, 1105 AZ, Amsterdam
D & A Research B.V.
Cardiology, Hegedyk 9, 8601 ZR, Sneek
NZOZ "ALL-MED" Centrum Medyczne Specjalistyczne Gabinety Lekarskie Marcin Ogorek
Outpatient clinic, ul. Armii Krajowej 43A, 94-046, Lodz
Centrum Medyczne Intercor Sp. z o.o.
Outpatient clinic, Ul. Kasztanowa 57, 85-605, Bydgoszcz
Centrum Medyczne Medyk Sp. z o.o. S.K.
Outpatient clinic, Ul. Fryderyka Szopena 1, 35-055, Rzeszow
Ko-Med Centra Kliniczne Sp. z o.o.
Outpatient clinic, Ul. Waclawa Sieroszewskiego 34, 24-100, Pulawy
Instytut Centrum Zdrowia Matki Polki
Klinika Kardiologii i Wad Wrodzonych Dorosłych, Ul. Rzgowska 281/289, 93-338, Lodz
Praktyka Lekarska Ewa Krzyzagorska
Outpatient clinic, Ul. Murawa 37a, 61-655, Poznan
Medicome Sp. z o.o.
Outpatient clinic, Plac Tadeusza Kosciuszki 12, 32-600, Oswiecim
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Hungary | 2024-07-04 | 2025-12-02 | 2024-07-04 | 2024-07-04 | |
| Netherlands | 2024-07-04 | 2026-01-11 | 2024-07-04 | 2024-07-04 | |
| Poland | 2024-07-23 | 2026-02-19 | 2024-07-23 | 2024-07-23 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 27 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_ Protocol Clarification Letter_2024-511331-96_for publication | 4.0 |
| Protocol (for publication) | D1_Protocol_2024-511331-96_for publication | 4.0 |
| Recruitment arrangements (for publication) | K_Recruitment Arrangements_public | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_public | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main ICF__TC_redacted | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main ICF_CL_redacted | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main ICF_redacted | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main ICF_TC_redacted | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_Redacted | 4.4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_Subject Specific_redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_New Information Addendum_CL_public | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_New Information Addendum_TC_public | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_New Information Addendum_version_public | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Pregnancy_redacted | 1.2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Pregnant Participant ICF_redacted | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Pregnant Participant ICF_Redacted | 1.1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Pregnant Partner ICF_redacted | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Pregnant Partner ICF_Redacted | 1.1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Statement_Public | 1.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_PFS Standalone Instructions for Use_public | 1.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_PFS Standalone Instructions for Use_public | 1.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_EN_2024-511331-96_for publication | 3.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_HU_2024-511331-96_for publication | 3. |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_NL_2024-511331-96_for publication | 3.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_PL_2024-511331-96_for publication | 3.0 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-05-21 | Netherlands | Acceptable with conditions 2024-07-04
|
2024-07-04 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-08-08 | Netherlands | Acceptable with conditions 2024-07-04
|
2024-08-08 |
| 3 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-05-29 | Netherlands | Acceptable with conditions 2025-08-26
|
2025-08-26 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-10-20 | Netherlands | Acceptable with conditions 2025-08-26
|
2025-10-20 |