An Extension Study of Donidalorsen (IONIS-PKK-LRx) in Participants With Hereditary Angioedema

Ionis Pharmaceuticals, Inc.20 enrolled

Overview

The purpose of this study was to evaluate the safety and efficacy of extended dosing of donidalorsen administered subcutaneously (SC), with alternative dosing and/or dose frequency with donidalorsen in participants with hereditary angioedema (HAE).

This was an open-label extension study of donidalorsen in 20 participants with HAE. The length of participation in the study was approximately 68 weeks, which included an up to 4-week qualification period, a 52-week treatment period, and a 12-week post-treatment period. Following the Week 53 treatment period visit, participants received donidalorsen in an extended treatment period for up to an additional 156 weeks. Participants taking part in the extended treatment period entered the 12-week post-treatment period after completion of, or early termination from, the extended treatment period.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hereditary Angioedema

Interventions

DonidalorsenDRUG

Donidalorsen administered SC

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Satisfactory completion of ISIS 721744-CS2 (index study) through Week 17 with an acceptable safety and tolerability profile, per Sponsor and Investigator judgement 2. Able and willing to participate in a 64-week study 3. Females must be non-pregnant, non-lactating and either surgically sterile or post-menopausal 4. Males must be surgically sterile or abstinent\* or if engaged in sexual relations with a female of child-bearing potential, participant is utilizing an acceptable contraceptive method 5. Participants must have access to, and the ability to use, ≥ 1 acute medication(s) (e.g., plasma-derived or recombinant C1- inhibitor (C1-INH) concentrate or a bradykinin-2 \[BK-2\] antagonist) to treat angioedema attacks Exclusion Criteria: 1\. Have any new condition or worsening of an existing condition or change or anticipated change in medication, which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study

Locations (7)

Ionis Investigative Site

Scottsdale, Arizona, United States

Ionis Investigative Site

Santa Monica, California, United States

Ionis Investigative Site

Plymouth, Minnesota, United States

Ionis Investigative Site

Cincinnati, Ohio, United States

Outcomes

Primary Outcomes

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)

An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not the AE is considered related to the medicinal (investigational) product. TEAEs were defined as those AEs that either started or worsened in severity on or after the date/time of first administration of study drug in this OLE Study. TEAEs included both serious and non-serious TEAEs.

Time frame: Up to Week 221

Percentage of Participants With Clinically Meaningful Changes in Clinical Laboratory Assessments

Clinical laboratory tests including clinical chemistry, hematology, coagulation, complement, inflammatory, urinalysis were performed. The percentage of participants with clinically meaningful changes were reported. Clinical meaningfulness was determined by the investigator.

Time frame: Up to Week 221

Percentage of Participants With Clinically Meaningful Changes in Vital Signs

Vital sign measurements including heart rate, respiratory rate, body temperature, systolic and diastolic blood pressure and pulse pressure were assessed. Percentage of participants with clinically meaningful changes in the vital signs were reported. Clinically meaningfulness was determined by the investigator.

Time frame: Up to Week 221

Percentage of Participants With Clinically Meaningful Changes in Electrocardiograms (ECGs) Parameters

The ECG parameters included ventricular rate, PR interval, QRS duration, QTc, QT corrected using the Fridericia's formula (QTcF), QT corrected using the Bazett's formula (QTcB), and overall interpretation. Percentage of participants with clinically meaningful changes in the ECG parameters were reported. Clinical meaningfulness was determined by the investigator.

Time frame: Up to Week 221

Percentage of Participants Who Received At Least One Concomitant Medication

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

Percent Change From Baseline in Time-normalized HAE Attack (Per 4 Weeks) Rate

HAE attack rate was calculated for each participant as the number of HAE attacks occurring during the respective period divided by the number of days the participant contributed to this period multiplied by 28 days. An HAE attack was defined as an event with signs or symptoms consistent with an attack in at least 1 of the locations: peripheral angioedema (cutaneous swelling involving an extremity, the face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain, with or without abdominal distention, nausea, vomiting, or diarrhea), laryngeal angioedema (stridor, dyspnea, difficulty speaking, difficulty swallowing, throat tightening, or swelling of the tongue, palate, uvula, or larynx). A negative change from baseline in HAE attacks indicates an improvement in HAE attacks.

Time frame: Up to Week 221

Percentage of Participants Who Used On-demand Medications

The most commonly used on-demand medications during the On-Treatment Period were C1 esterase inhibitors (human) and icatibant, which were allowed per-protocol for treatment of acute attacks.

Time frame: Up to Week 221