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A Study to Assess the Clinical Efficacy of IONIS-PKK-LRx in Participants With Hereditary Angioedema

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04030598
Recruitment Status : Recruiting
First Posted : July 24, 2019
Last Update Posted : July 2, 2020
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

Brief Summary:
The purpose of this study is to evaluate the clinical efficacy, safety, and tolerability of IONIS-PKK-LRx 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 IONIS-PKK-LRx on plasma prekallikrein (PKK) and other relevant biomarkers.

Condition or disease Intervention/treatment Phase
Hereditary Angioedema Drug: IONIS-PKK-LRx Drug: Placebo Phase 2

Detailed Description:
This is a randomized, double-blind, placebo-controlled, study in up 24 participants and will be conducted concurrently in 2 parts (Part A and Part B); participants will be 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 will be randomized, double-blind, and placebo-controlled; and Part B will be open-label. The length of participation in the study will be approximately 8 months, which includes an up to 8-week screening period, a 12-week treatment period, and a 13-week post-treatment period.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: Part A will be randomized, double-blind; Part B will be open-label.
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study to Assess the Clinical Efficacy of ISIS 721744, a Second-Generation Ligand-Conjugated Antisense Inhibitor of Prekallikrein, in Patients With Hereditary Angioedema
Actual Study Start Date : October 31, 2019
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: IONIS-PKK-LRx (Part A)
IONIS-PKK-LRx administered subcutaneously (SC) to participants with HAE-1/HAE-2 every 4 weeks for up to 12 weeks.
Drug: IONIS-PKK-LRx
IONIS-PKK-LRx administered SC
Other Name: ISIS 721744

Experimental: IONIS-PKK-LRx (Part B)
IONIS-PKK-LRx administered SC to participants with HAE-nC1-INH every 4 weeks for up to 12 weeks.
Drug: IONIS-PKK-LRx
IONIS-PKK-LRx administered SC
Other Name: ISIS 721744

Placebo Comparator: Placebo
Placebo will be administered SC to HAE-1/HAE-2 participants every 4 weeks for up to 12 weeks during Part A.
Drug: Placebo
Placebo matching solution administered SC




Primary Outcome Measures :
  1. Time-normalized Number of HAE Attacks (per Month) from Week 1 to Week 17 [ Time Frame: Week 1 to Week 17 ]

Secondary Outcome Measures :
  1. Time-normalized Number of HAE Attacks (per Month) from Week 5 to Week 17 [ Time Frame: Week 5 to Week 17 ]
  2. Time-normalized Number of Moderate or Severe HAE Attacks (per Month) from Week 5 to Week 17 [ Time Frame: Week 5 to Week 17 ]
  3. Number of Participants with Clinical Response by Week 17 [ Time Frame: Week 17 ]
    Clinical Response is defined as a ≥ 50%, ≥ 70%, or ≥ 90% reduction from baseline in HAE attack rate.

  4. Number of HAE Attacks Requiring Acute Therapy from Week 5 to Week 17 [ Time Frame: Week 5 to Week 17 ]
  5. Cleaved High Molecular Weight Kininogen (cHK) Levels at Weeks 9 and 17 [ Time Frame: Weeks 9 and 17 ]
  6. Prekallikrein (PKK) Activity at Weeks 9 and 17 [ Time Frame: Weeks 9 and 17 ]
  7. Consumption of On-demand Medication at Weeks 9 and 17 [ Time Frame: Weeks 9 and 17 ]
  8. Angioedema Quality of Life (AE-QoL) Questionnaire Score at Weeks 9 and 17 [ Time Frame: Weeks 9 and 17 ]
    The AE-QoL was developed to measure health-related quality of life (HRQoL) impairment in participants with recurrent angioedema. The AE-QoL is a self-administered questionnaire that can be completed in less than 5 minutes. It comprises 17 items across 4 domains: functioning, fatigue/mood, fears/shame, and food. Responses use a 5-point Likert scale ranging from 'never' to 'very often.' Global and domain scores range from 0 to 100, with higher scores indicating greater impairment.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 experience 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04030598


Contacts
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Contact: Ionis Pharmaceuticals 800-679-4747 patients@ionisph.com

Locations
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United States, California
University of California San Diego (UCSD) Recruiting
San Diego, California, United States, 92122
AIRE Medical of Los Angeles Recruiting
Santa Monica, California, United States, 90404
United States, Minnesota
Midwest Immunology Clinical Recruiting
Plymouth, Minnesota, United States, 55446
United States, Ohio
Bernstein Clinical Research Center, LLC Recruiting
Cincinnati, Ohio, United States, 45231
United States, Pennsylvania
Penn State Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033
United States, Texas
AARA Research Center Recruiting
Dallas, Texas, United States, 75231
Netherlands
Amsterdam UMC, loc. AMC Recruiting
Amsterdam, Netherlands, 1105 AZ
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
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Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04030598    
Other Study ID Numbers: ISIS 721744-CS2
2019-001044-22 ( EudraCT Number )
First Posted: July 24, 2019    Key Record Dates
Last Update Posted: July 2, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Ionis Pharmaceuticals, Inc.:
IONIS PKK-LRx
Additional relevant MeSH terms:
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Angioedema
Angioedemas, Hereditary
Vascular Diseases
Cardiovascular Diseases
Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Genetic Diseases, Inborn