Study to Assess the Long-Term Safety and Efficacy of ION-682884 in Patients with Hereditary Transthyretin-Mediated Amyloid Polyneuropathy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ionis Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

13 Jun 2022 → ongoing

Decision date (initial)

2024-08-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Ionis Pharmaceuticals, Inc.

External identifiers

EU CT number

2024-511201-32-00

EudraCT number

2021-001427-40

ClinicalTrials.gov

NCT05071300

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective is to evaluate the safety and tolerability of extended dosing with ION-682884 (eplontersen) in patients with hereditary transthyretin-mediated amyloid polyneuropathy (hATTR-PN)

Secondary objectives 1

1. The secondary objective is to evaluate the efficacy of extended dosing with ION-682884.

Conditions and MedDRA coding

Hereditary Transthyretin-Mediated Amyloid Polyneuropathy

Study design 2 periods

Regulatory references

Plan to share IPD

Yes

IPD plan description

Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Satisfactory completion of ION-682884-CS3 as judged by the Investigator and Sponsor, OR diagnosis of ATTRv-PN and satisfactory completion of study ISIS 420915-CS101 (an Investigator-Sponsored study with inotersen - the unconjugated version of ION-682884) as judged by the Investigator and Sponsor
2. Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements
3. Satisfy the following: a. Females: must be non-pregnant and non-lactating and either: − Surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) − Post-menopausal (defined as 12 months of spontaneous amenorrhea in females > 55 years of age or, in females ≤ 55 years, 12 months of spontaneous amenorrhea without an alternative medical cause and FSH levels in the postmenopausal range for the laboratory involved) − Abstinent*or − If engaged in sexual relations of child-bearing potential, agree to use highly effective contraceptive methods (Section 6.4.1) from the time of signing the informed consent form until at least 24 weeks after the last dose of ION-682884 and agree to receive pregnancy tests per protocol b. Males: Surgically sterile (i.e., bilateral orchidectomy) or abstinent*, if engaged in sexual relations with a woman of child-bearing potential (WOCBP), the patient's non-pregnant female partner must use a highly effective contraceptive method (Section 6.4.1) from the time of signing the informed consent form until at least 24 weeks after the last dose of ION-682884 *Abstinence (i.e., refraining from heterosexual intercourse throughout the duration of study participation) is only acceptable as true abstinence, i.e., when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial and withdrawal are not acceptable methods of contraception.
4. Willingness to adhere to vitamin A supplementation per protocol

Exclusion criteria 1

1. Have any new condition or worsening of existing condition that in the opinion of the Investigator or Sponsor would make the patient unsuitable for enrollment, or could interfere with the patient participating in or completing the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The primary endpoints (PEP) are change from Baseline (Index Study Baseline and separately open-label extension [OLE] Baseline) in the following measures: • Platelet count, renal function and transaminases • Adverse events (AE) • Use of concomitant medications • Vital signs and weight • Physical examination findings • Clinical laboratory tests • Electrocardiogram (ECG) parameters
2. The primary endpoints (PEP) are change from Baseline (Index Study Baseline and separately open-label extension [OLE] Baseline) in the following measures: • Thyroid panel tests • Coagulation tests • Inflammatory panel tests • Complement and immunogenicity tests

Secondary endpoints 3

1. The secondary endpoints are Change from Baseline (Index Study Baseline and separately OLE Baseline) in the following measures: • Neuropathy Impairment Score (NIS) • Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire
2. The secondary endpoints are Change from Baseline (Index Study Baseline and separately OLE Baseline) in the following measures: Neuropathy Symptom and Change score (NSC) • Serum Transthyretin (TTR) concentration • Physical Component Summary score (PCS) of 36-Item Short Form Survey (SF-36)
3. The secondary endpoints are Change from Baseline (Index Study Baseline and separately OLE Baseline) in the following measures: • Polyneuropathy disability score (PND) • Modified body mass index (mBMI) • Composite Autonomic Symptom Score-31 (COMPASS-31) • 5 Level EQ-5D (EQ-5D-5L)

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ionis Pharmaceuticals Inc.

Sponsor organisation

Ionis Pharmaceuticals Inc.

Address

2855 Gazelle Court

City

Carlsbad

Postcode

92010-6670

Country

United States

Scientific contact point

Organisation

Ionis Pharmaceuticals Inc.

Contact name

Ionis Pharmaceuticals Inc.

Public contact point

Organisation

Ionis Pharmaceuticals Inc.

Contact name

Ionis Pharmaceuticals Inc.

Third parties 11

Locations

7 EU/EEA countries · 12 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 45 files

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

Application history

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