A Study to Assess the Clinical Efficacy of Donidalorsen (Also Known as IONIS-PKK-LRx and ISIS 721744) in Participants With Hereditary Angioedema

Ionis Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Hereditary Angioedema

Treatments: Drug: Donidalorsen; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04030598

ISIS 721744-CS2

2019-001044-22 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study was to evaluate the clinical efficacy, safety, and tolerability of donidalorsen in participants with hereditary angioedema (HAE) type 1 (HAE-1), HAE type 2 (HAE-2), or HAE with normal C1-inhibitor (C1-INH) and to evaluate the effect of donidalorsen on plasma prekallikrein (PKK) and other relevant biomarkers.

Full description

This was a randomized, double-blind, placebo-controlled study in 23 participants conducted concurrently in 2 parts (Part A and Part B); participants were allocated into Part A or Part B according to type of HAE (i.e., either HAE-1/HAE-2 in Part A or HAE-nC1-INH in Part B). Part A was randomized, double-blind, and placebo-controlled; and Part B was open-label. The length of participation in the study was approximately 8 months, which included an up to 8-week screening period, a 12-week treatment period, and a 13-week post-treatment period.

Enrollment: 23 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Documented diagnosis of HAE-1/HAE-2 (for inclusion in Part A) or HAE-nC1-INH (for inclusion in Part B)
• Participants must have experienced a minimum of 2 HAE attacks (assessed by the Angioedema Activity Score [AAS] and confirmed by the investigator) during the screening period
• Access to, and the ability to use, ≥ 1 acute medication(s) to treat angioedema attacks

Exclusion criteria

• Anticipated use of short-term prophylaxis for angioedema attacks for a pre-planned procedure during the screening or study periods

• Concurrent diagnosis of any other type of recurrent angioedema, including acquired or idiopathic angioedema

• Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C, or chronic hepatitis B

• Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated

• Treatment with another investigational drug or biological agent within 1 month or 5 half-lives, whichever is longer, of screening

• Exposure to any of the following medications:

  • Angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption (such as oral contraceptive or hormonal replacement therapy) within 4 weeks prior to screening
  • Chronic prophylaxis with Lanadelumab within 10 weeks prior to screening
  • Oligonucleotides (including small interfering ribonucleic acid [RNA]) within 4 months of screening (if single dose received) or within 12 months of screening (if multiple doses received)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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23 participants in 3 patient groups, including a placebo group

Part A: Placebo

Placebo Comparator group

Description:

Participants with hereditary angioedema type I/type II (HAE-1/HAE-2) received placebo subcutaneously (SC) every 4 weeks at Weeks 1, 5, 9, and 13.

Treatment:

Drug: Placebo

Part A: Donidalorsen 80 mg

Experimental group

Description:

Participants with HAE-1/HAE-2 received donidalorsen, 80 mg, SC, every 4 weeks at Weeks 1, 5, 9, and 13.

Treatment:

Drug: Donidalorsen

Part B: Donidalorsen 80 mg

Experimental group

Description:

Participants with hereditary angioedema with normal C1-inhibitor (HAE-nC1-INH) received donidalorsen, 80 mg, SC, every 4 weeks at Weeks 1, 5, 9, and 13.

Treatment:

Drug: Donidalorsen