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

Sponsor
Ionis Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT04030598
Collaborator
(none)
29
Enrollment
8
Locations
3
Arms
16
Actual Duration (Months)
3.6
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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
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.

Study Design

Study Type:
Interventional
Actual Enrollment :
29 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 :
Oct 31, 2019
Actual Primary Completion Date :
Feb 1, 2021
Actual Study Completion Date :
Mar 1, 2021

Arms and Interventions

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 Names:
  • 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 Names:
  • 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

    Outcome Measures

    Primary Outcome Measures

    1. Time-normalized Number of HAE Attacks (per Month) from Week 1 to Week 17 [Week 1 to Week 17]

    Secondary Outcome Measures

    1. Time-normalized Number of HAE Attacks (per Month) from Week 5 to Week 17 [Week 5 to Week 17]

    2. Time-normalized Number of Moderate or Severe HAE Attacks (per Month) from Week 5 to Week 17 [Week 5 to Week 17]

    3. Number of Participants with Clinical Response by Week 17 [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 [Week 5 to Week 17]

    5. Cleaved High Molecular Weight Kininogen (cHK) Levels at Weeks 9 and 17 [Weeks 9 and 17]

    6. Prekallikrein (PKK) Activity at Weeks 9 and 17 [Weeks 9 and 17]

    7. Consumption of On-demand Medication at Weeks 9 and 17 [Weeks 9 and 17]

    8. Angioedema Quality of Life (AE-QoL) Questionnaire Score at Weeks 9 and 17 [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Medical Research of Arizona Scottsdale Arizona United States 85251
    2 University of California San Diego (UCSD) San Diego California United States 92122
    3 AIRE Medical of Los Angeles Santa Monica California United States 90404
    4 Midwest Immunology Clinical Plymouth Minnesota United States 55446
    5 Bernstein Clinical Research Center, LLC Cincinnati Ohio United States 45231
    6 Penn State Hershey Medical Center Hershey Pennsylvania United States 17033
    7 AARA Research Center Dallas Texas United States 75231
    8 Amsterdam UMC, loc. AMC Amsterdam Netherlands 1105 AZ

    Sponsors and Collaborators

    • Ionis Pharmaceuticals, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Ionis Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT04030598
    Other Study ID Numbers:
    • ISIS 721744-CS2
    • 2019-001044-22
    First Posted:
    Jul 24, 2019
    Last Update Posted:
    May 14, 2021
    Last Verified:
    May 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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:
    Angioedema
    Angioedemas, Hereditary

    Study Results

    No Results Posted as of May 14, 2021