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Single Arm, Open Label Trial With Iptacopan Treatment for 24 Weeks, in Patients on Stable Regimen of Anti-C5 Who Switch to Iptacopan. (APPULSE)

Primary Purpose

Paroxysmal Nocturnal Hemoglobinuria

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Iptacopan
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria focused on measuring Paroxysmal Nocturnal Hemoglobinuria, iptacopan, single arm open-label, Hb≥10 g/dL in response to anti-C5 antibody, switch to iptacopan, PNH, LNP023

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study. Male and female participants ≥ 18 years of age, at the time of ICF signatures and with a diagnosis of PNH confirmed by treating physician. Stable regimen (dose and intervals) of anti-C5 antibody treatment (either eculizumab or ravulizumab) for at least 6 months prior to screening Mean hemoglobin level ≥10 g/dL Vaccination against Neisseria meningitidis and S. pneumoniae infection are required prior to the start of iptacopan treatment. If not received previously, vaccination against Haemophilus influenzae infections is recommended, if available and according to local regulations. Ability to communicate well with the investigator, to understand and comply with the requirements of the study Other protocol -defined inclusion criteria may apply at the end. Exclusion Criteria: Participation in any other investigational drug trial or use of other investigational drugs at the time of enrollment Patients requiring red blood cell transfusion in the 6 months prior to screening or during screening History of stem cell transplantation or any solid organ transplantation Active systemic bacterial, viral (incl. COVID-19) or fungal infection within 14 days prior to study drug administration Presence of fever ≥ 38.0 °C (100.4 °F) within 7 days prior to study drug administration Human immunodeficiency virus (HIV) infection (known history of HIV or test positive for HIV antibody at Screening) A history of recurrent invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus Unstable medical condition including, but not limited to, myocardial ischemia, active gastrointestinal bleeding, coexisting chronic anemia unrelated to PNH, or unstable thrombotic event not amenable to active treatment as judged by the investigator at Screening. History of cancer of any part of the body within the past 5 years, Ongoing drug or alcohol abuse that could interfere with patient's participation in the trial. Any medical condition deemed likely to interfere with the patient's participation in the study Female patients who are pregnant or breastfeeding, or intending to conceive during the course of the study

Sites / Locations

  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Iptacopan treatment in adult PNH patients

Arm Description

Subjects will receive iptacopan at a dose of 200 mg b.i.d. orally

Outcomes

Primary Outcome Measures

Change from baseline in Hb levels to demonstrate non-inferiority of iptacopan
To assess the efficacy of iptacopan after 24 weeks of treatment in PNH patients who switch to iptacopan from prior SoC

Secondary Outcome Measures

Change in Hb levels to demonstrate superiority of iptacopan
To assess efficacy of iptacopan after 24 weeks of treatment in PNH patients who switch to iptacopan from prior SoC
Percentage of hematological responders to iptacopan treatment
Percentage of hematological responders to iptacopan treatment will be collected
Change from baseline in Absolute Reticulocytes count (ARC) levels
To assess the effect of iptacopan on markers of Extravascular Hemolysis (EVH) and Intravascular Hemolysis (IVH).
Percentage change from baseline in lactate dehydrogenase (LDH) levels
To assess the effect of iptacopan on markers of EVH and IVH.
Change in treatment satisfaction score using TSQM-9 questionnaire
TSQM-9 is a patient reported outcomes measure that was designed to assess patients' satisfaction with medication across three domains of effectiveness, convenience and global satisfaction. The TSQM-9 contains 3 questions in each domain. Domain scores range from 0 - 100 with higher representing better scores for the domain.
Change in fatigue score using FACIT-F questionnaire
The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. All FACIT scales are scored so that a high score is better. As each of the 13 items of the FACIT-Fatigue scale ranges from 0-4, the range of possible scores is 0-52, with 0 being the worst possible score and 52 the best.
Rate of Breakthrough hemolysis (BTH)
Occurrence of BTH reported from D1 to D168
Rate of Major Adverse Vascular Events (MAVEs)
Occurrence of MAVEs reported from D1 to D168

Full Information

First Posted
November 18, 2022
Last Updated
October 17, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT05630001
Brief Title
Single Arm, Open Label Trial With Iptacopan Treatment for 24 Weeks, in Patients on Stable Regimen of Anti-C5 Who Switch to Iptacopan.
Acronym
APPULSE
Official Title
A Multicenter, Single Arm, Open-label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily Iptacopan in Adult PNH Patients Who Have Hb≥10 g/dL in Response to Anti-C5 Antibody and Switch to Iptacopan
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 24, 2023 (Actual)
Primary Completion Date
January 8, 2025 (Anticipated)
Study Completion Date
January 9, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of the study is to find out if iptacopan is effective and safe in adult patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) who switch from their current standard of care treatment (eculizumab or ravulizumab) to study treatment, iptacopan/LNP023.
Detailed Description
This is a multicenter, single-arm, open label trial, with iptacopan treatment for 24 weeks in adult PNH patients. This study is comprised of two periods: A Screening period lasting up to 8 weeks. A 24-week open-label, iptacopan Treatment period. After completion of the treatment period, participants who continue to benefit from the iptacopan treatment based on the study doctor's evaluation will be able to join the Roll-over extension study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paroxysmal Nocturnal Hemoglobinuria
Keywords
Paroxysmal Nocturnal Hemoglobinuria, iptacopan, single arm open-label, Hb≥10 g/dL in response to anti-C5 antibody, switch to iptacopan, PNH, LNP023

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Model Description
A multicenter, single arm, open-label trial to evaluate efficacy and safety of oral, twice daily iptacopan in adult PNH patients who have Hb≥10 g/dL in response to anti-C5 antibody and switch to iptacopan
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Iptacopan treatment in adult PNH patients
Arm Type
Experimental
Arm Description
Subjects will receive iptacopan at a dose of 200 mg b.i.d. orally
Intervention Type
Drug
Intervention Name(s)
Iptacopan
Intervention Description
Treatment with iptacopan at a dose of 200 mg b.i.d. will start on the first day (Day 1) and continue for 24 weeks.
Primary Outcome Measure Information:
Title
Change from baseline in Hb levels to demonstrate non-inferiority of iptacopan
Description
To assess the efficacy of iptacopan after 24 weeks of treatment in PNH patients who switch to iptacopan from prior SoC
Time Frame
Up to 168 days
Secondary Outcome Measure Information:
Title
Change in Hb levels to demonstrate superiority of iptacopan
Description
To assess efficacy of iptacopan after 24 weeks of treatment in PNH patients who switch to iptacopan from prior SoC
Time Frame
Up to 168 days
Title
Percentage of hematological responders to iptacopan treatment
Description
Percentage of hematological responders to iptacopan treatment will be collected
Time Frame
Up to 168 days
Title
Change from baseline in Absolute Reticulocytes count (ARC) levels
Description
To assess the effect of iptacopan on markers of Extravascular Hemolysis (EVH) and Intravascular Hemolysis (IVH).
Time Frame
Up to 168 days
Title
Percentage change from baseline in lactate dehydrogenase (LDH) levels
Description
To assess the effect of iptacopan on markers of EVH and IVH.
Time Frame
Up to 168 days
Title
Change in treatment satisfaction score using TSQM-9 questionnaire
Description
TSQM-9 is a patient reported outcomes measure that was designed to assess patients' satisfaction with medication across three domains of effectiveness, convenience and global satisfaction. The TSQM-9 contains 3 questions in each domain. Domain scores range from 0 - 100 with higher representing better scores for the domain.
Time Frame
Up to 168 days
Title
Change in fatigue score using FACIT-F questionnaire
Description
The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. All FACIT scales are scored so that a high score is better. As each of the 13 items of the FACIT-Fatigue scale ranges from 0-4, the range of possible scores is 0-52, with 0 being the worst possible score and 52 the best.
Time Frame
Up to 168 days
Title
Rate of Breakthrough hemolysis (BTH)
Description
Occurrence of BTH reported from D1 to D168
Time Frame
24 weeks
Title
Rate of Major Adverse Vascular Events (MAVEs)
Description
Occurrence of MAVEs reported from D1 to D168
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study. Male and female participants ≥ 18 years of age, at the time of ICF signatures and with a diagnosis of PNH confirmed by treating physician. Stable regimen (dose and intervals) of anti-C5 antibody treatment (either eculizumab or ravulizumab) for at least 6 months prior to screening Mean hemoglobin level ≥10 g/dL Vaccination against Neisseria meningitidis and S. pneumoniae infection are required prior to the start of iptacopan treatment. If not received previously, vaccination against Haemophilus influenzae infections is recommended, if available and according to local regulations. Ability to communicate well with the investigator, to understand and comply with the requirements of the study Other protocol -defined inclusion criteria may apply at the end. Exclusion Criteria: Participation in any other investigational drug trial or use of other investigational drugs at the time of enrollment Patients requiring red blood cell transfusion in the 6 months prior to screening or during screening History of stem cell transplantation or any solid organ transplantation Active systemic bacterial, viral (incl. COVID-19) or fungal infection within 14 days prior to study drug administration Presence of fever ≥ 38.0 °C (100.4 °F) within 7 days prior to study drug administration Human immunodeficiency virus (HIV) infection (known history of HIV or test positive for HIV antibody at Screening) A history of recurrent invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus Unstable medical condition including, but not limited to, myocardial ischemia, active gastrointestinal bleeding, coexisting chronic anemia unrelated to PNH, or unstable thrombotic event not amenable to active treatment as judged by the investigator at Screening. History of cancer of any part of the body within the past 5 years, Ongoing drug or alcohol abuse that could interfere with patient's participation in the trial. Any medical condition deemed likely to interfere with the patient's participation in the study Female patients who are pregnant or breastfeeding, or intending to conceive during the course of the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
1-888-669-6682
Email
novartis.email@novartis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
+41613241111
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Cerritos
State/Province
California
ZIP/Postal Code
90703
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Torrance
State/Province
California
ZIP/Postal Code
90509-2910
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Miami Lakes
State/Province
Florida
ZIP/Postal Code
33014
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01665
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Nantes Cedex 1
ZIP/Postal Code
44093
Country
France
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Nice
ZIP/Postal Code
06202
Country
France
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Paris 10
ZIP/Postal Code
75475
Country
France
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Aydin
ZIP/Postal Code
09100
Country
Turkey
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Learn more about this trial

Single Arm, Open Label Trial With Iptacopan Treatment for 24 Weeks, in Patients on Stable Regimen of Anti-C5 Who Switch to Iptacopan.

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