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Study of Efficacy and Safety of Twice Daily Oral Iptacopan (LNP023) in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy (APPOINT-PNH)

Primary Purpose

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Iptacopan (LNP023)
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria (PNH) focused on measuring Paroxysmal nocturnal hemoglobinuria, Hemoglobin, Anemia, LNP023, Iptacopan

Eligibility Criteria

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

Inclusion Criteria:

  • Male and female participants ≥ 18 years of age with a diagnosis of PNH confirmed by high-sensitivity flow cytometry with clone size ≥ 10%
  • Mean hemoglobin level <10 g/dL
  • LDH > 1.5 x Upper Limit of Normal (ULN)
  • Vaccination against Neisseria meningitidis infection is required prior to the start of study treatment
  • If not received previously, vaccination against Streptococcus pneumoniae and Haemophilus influenzae infections should be given

Exclusion Criteria:

  • Prior treatment with a complement inhibitor, including anti-C5 antibody
  • Known or suspected hereditary complement deficiency
  • History of hematopoietic stem cell transplantation
  • Patients with laboratory evidence of bone marrow failure (reticulocytes <100x109/L; platelets <30x109/L; neutrophils <0.5x109/L).
  • Active systemic bacterial, viral (incl. COVID-19)or fungal infection within 14 days prior to study drug administration.
  • History of recurrent invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus.
  • Major concurrent comorbidities including but not limited to severe kidney disease (e.g., dialysis), advanced cardiac disease (e.g., NYHA class IV heart failure), severe pulmonary disease (e.g., severe pulmonary hypertension (WHO class IV)), or hepatic disease (e.g., active hepatitis) that in the opinion of the investigator precludes participant's participation in the study.

Other protocol defined inclusion/exclusion criteria may apply.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LNP023

Arm Description

Participants will receive LNP023 at a dose of 200 mg orally b.i.d

Outcomes

Primary Outcome Measures

Proportion of participants achieving a sustained increase in hemoglobin levels of ≥ 2 g/dL in the absence of red blood cell transfusion
Proportion of participants achieving a sustained increase from baseline in hemoglobin levels of ≥ 2 g/dL assessed , in the absence of red blood cell transfusions

Secondary Outcome Measures

Proportion of participants achieving sustained hemoglobin levels ≥ 12 g/dL in the absence of red blood cell transfusions
Proportion of participants achieving sustained hemoglobin levels ≥ 12 g/dL in absence of red blood cell transfusion
Transfusion avoidance (TA) defined as the proportion of participants who remain free from transfusions
Transfusion avoidance (TA) defined as the proportion of participants who remain free from transfusions
Change from baseline in hemoglobin
Change from baseline in hemoglobin (g/dL) as mean of visits between Day 126 and Day 168
Percent change from baseline in LDH
Percent change from baseline in LDH levels (U/L) as mean of visits between Day 126 and Day 168
Rate of breakthrough hemolysis (BTH)
Occurrences of breakthrough hemolysis reported between Day 1 and Day 168
Change from baseline in reticulocyte counts
Change from baseline in reticulocyte counts as mean of visits between Day 126 and Day 168
Change in fatigue score, using the FACIT-Fatigue questionnaire
Change from baseline in FACIT-Fatigue scores as mean of visits between Day 126 and Day 168
Rates of Major Adverse Vascular Events (MAVEs incl. thrombosis)
Occurrences of MAVEs occurring between Day 1 and Day 168

Full Information

First Posted
March 25, 2021
Last Updated
May 10, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT04820530
Brief Title
Study of Efficacy and Safety of Twice Daily Oral Iptacopan (LNP023) in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy
Acronym
APPOINT-PNH
Official Title
A Multicenter, Single-arm, Open-label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily Iptacopan in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
July 19, 2021 (Actual)
Primary Completion Date
November 2, 2022 (Actual)
Study Completion Date
April 18, 2023 (Actual)

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
Yes

5. Study Description

Brief Summary
The purpose of this Phase 3 study is to determine whether iptacopan is efficacious and safe for the treatment of PNH patients who are naive to complement inhibitor therapy.
Detailed Description
The purpose of this single arm, open label study is to determine whether iptacopan is efficacious and safe for the treatment of PNH patients who are naive to complement inhibitor therapy, including anti-C5 antibody. The study is planned to have approximately 40 PNH patients starting study treatment in various countries.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Keywords
Paroxysmal nocturnal hemoglobinuria, Hemoglobin, Anemia, LNP023, Iptacopan

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LNP023
Arm Type
Experimental
Arm Description
Participants will receive LNP023 at a dose of 200 mg orally b.i.d
Intervention Type
Drug
Intervention Name(s)
Iptacopan (LNP023)
Other Intervention Name(s)
Iptacopan
Intervention Description
Taken orally b.i.d. Dosage supplied: 200mg Dosage form: Hard gelatin capsule Route of Administration: oral
Primary Outcome Measure Information:
Title
Proportion of participants achieving a sustained increase in hemoglobin levels of ≥ 2 g/dL in the absence of red blood cell transfusion
Description
Proportion of participants achieving a sustained increase from baseline in hemoglobin levels of ≥ 2 g/dL assessed , in the absence of red blood cell transfusions
Time Frame
Day 168
Secondary Outcome Measure Information:
Title
Proportion of participants achieving sustained hemoglobin levels ≥ 12 g/dL in the absence of red blood cell transfusions
Description
Proportion of participants achieving sustained hemoglobin levels ≥ 12 g/dL in absence of red blood cell transfusion
Time Frame
Day 168
Title
Transfusion avoidance (TA) defined as the proportion of participants who remain free from transfusions
Description
Transfusion avoidance (TA) defined as the proportion of participants who remain free from transfusions
Time Frame
Day 14 and Day 168
Title
Change from baseline in hemoglobin
Description
Change from baseline in hemoglobin (g/dL) as mean of visits between Day 126 and Day 168
Time Frame
Day 126 and Day 168
Title
Percent change from baseline in LDH
Description
Percent change from baseline in LDH levels (U/L) as mean of visits between Day 126 and Day 168
Time Frame
Day 126 and Day 168
Title
Rate of breakthrough hemolysis (BTH)
Description
Occurrences of breakthrough hemolysis reported between Day 1 and Day 168
Time Frame
Day 1 and Day 168
Title
Change from baseline in reticulocyte counts
Description
Change from baseline in reticulocyte counts as mean of visits between Day 126 and Day 168
Time Frame
Day 126 and Day 168
Title
Change in fatigue score, using the FACIT-Fatigue questionnaire
Description
Change from baseline in FACIT-Fatigue scores as mean of visits between Day 126 and Day 168
Time Frame
Day 126 and Day 168
Title
Rates of Major Adverse Vascular Events (MAVEs incl. thrombosis)
Description
Occurrences of MAVEs occurring between Day 1 and Day 168
Time Frame
Day 1 and Day 168

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male and female participants ≥ 18 years of age with a diagnosis of PNH confirmed by high-sensitivity flow cytometry with clone size ≥ 10% Mean hemoglobin level <10 g/dL LDH > 1.5 x Upper Limit of Normal (ULN) Vaccination against Neisseria meningitidis infection is required prior to the start of study treatment If not received previously, vaccination against Streptococcus pneumoniae and Haemophilus influenzae infections should be given Exclusion Criteria: Prior treatment with a complement inhibitor, including anti-C5 antibody Known or suspected hereditary complement deficiency History of hematopoietic stem cell transplantation Patients with laboratory evidence of bone marrow failure (reticulocytes <100x109/L; platelets <30x109/L; neutrophils <0.5x109/L). Active systemic bacterial, viral (incl. COVID-19)or fungal infection within 14 days prior to study drug administration. History of recurrent invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus. Major concurrent comorbidities including but not limited to severe kidney disease (e.g., dialysis), advanced cardiac disease (e.g., NYHA class IV heart failure), severe pulmonary disease (e.g., severe pulmonary hypertension (WHO class IV)), or hepatic disease (e.g., active hepatitis) that in the opinion of the investigator precludes participant's participation in the study. Other protocol defined inclusion/exclusion criteria may apply.
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
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100730
Country
China
Facility Name
Novartis Investigative Site
City
Tianjin
ZIP/Postal Code
300052
Country
China
Facility Name
Novartis Investigative Site
City
Paris Cedex 10
ZIP/Postal Code
75475
Country
France
Facility Name
Novartis Investigative Site
City
Aachen
ZIP/Postal Code
52074
Country
Germany
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Avellino
State/Province
AV
ZIP/Postal Code
83100
Country
Italy
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Kota Kinabalu
State/Province
Sabah
ZIP/Postal Code
88586
Country
Malaysia
Facility Name
Novartis Investigative Site
City
Kuching
State/Province
Sarawak
ZIP/Postal Code
93586
Country
Malaysia
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
119228
Country
Singapore
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom

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

Study of Efficacy and Safety of Twice Daily Oral Iptacopan (LNP023) in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy

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