Clinical Trial Results:
An Open-Label, Pilot Study to assess the effect of Lanadelumab on the clinical signs and symptoms of Hereditary angioedema with normal C1-inhibitor / / LANC (Lanadelumab in Hereditary
Angioedema with normal C1-esterase inhibitor)
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Summary
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EudraCT number |
2018-004136-30 |
Trial protocol |
DE |
Global end of trial date |
03 Jul 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Jan 2026
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First version publication date |
15 Jan 2026
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
DEALSZ-2018-001
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Charité - Universitätsmedizin Berlin
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Sponsor organisation address |
Charitéplatz 1, Berlin, Germany, 10117
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Public contact |
Markus Magerl, Dpt. of Dermatology and Allergy, Campus Benjamin Franklin, 0049 030450 518043 , markus.magerl@charite.de
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Scientific contact |
Markus Magerl, Dpt. of Dermatology and Allergy, Campus Benjamin Franklin, 0049 030450 518043 , markus.magerl@charite.de
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 Jul 2025
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
03 Jul 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Jul 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the effect of Lanadelumab on the clinical signs and symptoms in patients with HAE-nC1.
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Protection of trial subjects |
The study was conducted in accordance with the ICH E6 (R2) Guideline for Good Clinical Practice (GCP), with applicable local regulations (including European Directive 2001/20/EC, German Medicinal
Products Act (AMG)), and with the ethical principles that have their origins in the Declaration of Helsinki (version 2013). The Investigator also had to comply with all applicable privacy regulations
(e.g., Regulation (EU) 2016/679 (General Data Protection Regulation, GDPR)).
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Background therapy |
Hereditary angioedema (HAE) is a rare genetic disease with an estimated prevalence in the general population of approximately 1:50.000. The disease is characterized by localized and self-limiting swelling of the subcutaneous and/or submucosal tissue without wheals or other signs of urticaria due to a temporary increase in vascular permeability caused by the release of vaso-active mediators. The clinical expression is highly variable, from asymptomatic cases to patients with disabling and life-threatening attacks, and it has a demonstrated humanistic and economic burden. Swelling attacks in patients with Hereditary Angioedema with normal C1 inhibitor (HAE-nC1INH) are caused by activation of the contact system and the subsequent generation of bradykinin, which causes extravasation by activating the bradykinin-B2 receptor. This pathomechanism is thought to also be involved in some types of HAE-nC1INH. Lanadelumab (Takhzyro, Takeda Pharmaceutical Company Limited) was approved in the United States in October 2018 by the Food and Drug Administration (FDA) and in November 2018 in Europe by the European Medicine Agency (EMA), for long-term prophylaxis in HAE in patients 12 years or older, with a later approval extending the indication to children aged 2 years and older. At the time this study was planned, there was only few data available on the efficacy and safety of Lanadelumab in patients with HAE-nC1INH. Therefore, the aim of this Phase 2, exploratory, proof-of concept, single-center, single-arm, open-label pilot interventional study was to assess the effects and safety of Lanadelumab in patients with HAE-nC1INH. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
24 Sep 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 5
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Worldwide total number of subjects |
5
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EEA total number of subjects |
5
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
5
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
5 patient with clinical symptoms of angioedema attacks (at least 2 attacks within the last 3 months prior to screening; and at least 2 attacks within 12 weeks at maximum in the run-in period) and documented HAE-nC1INH (history, a FXII / PLG / ANGPT1 / KNG1 / MYOF / HSST mutation ...) were enrolled and received treatment at one study site. | ||||||||||
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Pre-assignment
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Screening details |
The study consisted of a screening period of 4 to 12 weeks. 7 eligible patients were screened. 1 patients did not meet all eligibility criteria at Screening and 1 patient declined to participate. | ||||||||||
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Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||
Blinding implementation details |
this study was planned and conducted as a proof-of-concept, open-label, singlearm trial.
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Arms
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Arm title
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Treatment | ||||||||||
Arm description |
- | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Lanadelumab
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Investigational medicinal product code |
CAS Number 1426055-14-2
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Other name |
Takzhyro
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Patients received an injection of 300 mg Lanadelumab every 2 weeks.
Lanadelumab is a human monoclonal antibody (class IgG1 kappa) that targets plasma kallikrein (pKal)in order to promote prevention of angioedema in people with hereditary angioedema.
Before enrollment, patients were required to discontinue certain medications that could interfere with the investigational medicinal product or study endpoints, with a defined washout period implemented as needed. It was required that patients, at the time of enrollment, were not enrolled in another investigational treatment or device study and did not take any investigational agent for 4 weeks or 5 half-lives, whichever is longer, since the end of another investigational device or drug trial. The use of rescue medication was monitored and reviewed throughout the treatment period and if necessary, adjusted. The use of rescue medication was also part of the efficacy assessment.
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Treatment
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Reporting group description |
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End point title |
change of Angioedema Activity Score (AAS) [1] | ||||||||||||||||
End point description |
AAS28 ≥75% responders
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End point type |
Primary
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End point timeframe |
At week 48 compared to the AAS at week 0 (baseline).
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Due to the limited patient numbers of with Hereditary Angioedema with normal C1-esterase inhibitor, the sample size (n=5-7) is not based on statistical methodology but reflects the number of available patients at the center. |
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Attachments |
tables and charts _primary -secundary endpoints |
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| Notes [2] - after week 33 only 3 subjects were analysed, because of lost to follow up |
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| No statistical analyses for this end point | |||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
overall study
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22
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Reporting groups
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Reporting group title |
Treatment
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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14 Jun 2019 |
update protocol version 2.0,
• Correction of Sample size calculation
• “Investigator´s Brochure” replaced by “Specialist Information”
• Information on approval status of Lanadelumab added
• correction of study outline
• interim analysis removed
• Early study termination section specified
• Change in person Serious Adverse events must be reported to
• Addition of success criterion |
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20 Dec 2019 |
update protocol version 3.0
• Anti-drug antibody assessment deleted from synopsis
• Addition of newly found KNG1 mutation to table 1
• information on approval status of Lanadelumab was adjusted,
• Primary endpoint, secondary endpoints, statistical analyses and sample size calculation were adjusted
• Details for labelling of IMP were added
• Specification of early study termination criteria
• Adverse Event not used as abbreviations anymore to avoid confusion with Angioedema
• Adverse event reporting added at all timepoints in schedule of assessments
• Explanation of AAS and AE-QoL questionnaire expanded |
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28 Feb 2020 |
update protocol version 3.1:
• Success criterion added for 6 or 7 patients
• Sample size calculation amended for power analysis |
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22 Oct 2021 |
update protocol version 4.0:
• CentoCard® included for blood biomarkers
• Bilirubin to laboratory added
• Specification of MedDRA Version 22.0 |
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19 Apr 2023 |
update protocol version 5.0:
• Deletion of CentoCard® for blood biomarkers
• Adjustment of applicable legislation (no reference to US law)
• Three recently discovered mutations (KNG1, MYOF, HSST) added as inclusion criterion
• Update of Database Management and Quality Control (section 10.4) as well as Data Analysis (section 11) – paper CRF and SPSS will be used
• Adjustment of study termination criteria |
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06 Jul 2023 |
update protocol version 6.0:
• Adjustment of study termination criteria |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Due to the limited patient numbers of with Hereditary Angioedema with normal C1-esterase inhibitor, the sample size (n=5-7) is not based on statistical methodology but reflects the number of available patients at the center. | |||
