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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)

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ClinicalTrials.gov Identifier: NCT04820530
Recruitment Status : Recruiting
First Posted : March 29, 2021
Last Update Posted : September 13, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

Condition or disease Intervention/treatment Phase
Paroxysmal Nocturnal Hemoglobinuria (PNH) Drug: Iptacopan (LNP023) Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 19, 2021
Estimated Primary Completion Date : January 23, 2023
Estimated Study Completion Date : July 10, 2023


Arm Intervention/treatment
Experimental: LNP023
Participants will receive LNP023 at a dose of 200 mg orally b.i.d
Drug: Iptacopan (LNP023)
Taken orally b.i.d. Dosage supplied: 200mg Dosage form: Hard gelatin capsule Route of Administration: oral
Other Name: Iptacopan




Primary Outcome Measures :
  1. Proportion of participants achieving a sustained increase in hemoglobin levels of ≥ 2 g/dL in the absence of red blood cell transfusion [ Time Frame: Day 168 ]
    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 :
  1. Proportion of participants achieving sustained hemoglobin levels ≥ 12 g/dL in the absence of red blood cell transfusions [ Time Frame: Day 168 ]
    Proportion of participants achieving sustained hemoglobin levels ≥ 12 g/dL in absence of red blood cell transfusion

  2. Transfusion avoidance (TA) defined as the proportion of participants who remain free from transfusions [ Time Frame: Day 14 and Day 168 ]
    Transfusion avoidance (TA) defined as the proportion of participants who remain free from transfusions

  3. Change from baseline in hemoglobin [ Time Frame: Day 126 and Day 168 ]
    Change from baseline in hemoglobin (g/dL) as mean of visits between Day 126 and Day 168

  4. Percent change from baseline in LDH [ Time Frame: Day 126 and Day 168 ]
    Percent change from baseline in LDH levels (U/L) as mean of visits between Day 126 and Day 168

  5. Rate of breakthrough hemolysis (BTH) [ Time Frame: Day 1 and Day 168 ]
    Occurrences of breakthrough hemolysis reported between Day 1 and Day 168

  6. Change from baseline in reticulocyte counts [ Time Frame: Day 126 and Day 168 ]
    Change from baseline in reticulocyte counts as mean of visits between Day 126 and Day 168

  7. Change in fatigue score, using the FACIT-Fatigue questionnaire [ Time Frame: Day 126 and Day 168 ]
    Change from baseline in FACIT-Fatigue scores as mean of visits between Day 126 and Day 168

  8. Rates of Major Adverse Vascular Events (MAVEs incl. thrombosis) [ Time Frame: Day 1 and Day 168 ]
    Occurrences of MAVEs occurring between Day 1 and Day 168



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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:

  • 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.


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): NCT04820530


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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France
Novartis Investigative Site Recruiting
Paris, France, 75010
Japan
Novartis Investigative Site Recruiting
Shinagawa ku, Tokyo, Japan, 141 8625
Novartis Investigative Site Recruiting
Shinjuku-ku, Tokyo, Japan, 160-0023
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 169608
United Kingdom
Novartis Investigative Site Recruiting
London, United Kingdom, SE5 9RS
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04820530    
Other Study ID Numbers: CLNP023C12301
2020-003172-41 ( EudraCT Number )
First Posted: March 29, 2021    Key Record Dates
Last Update Posted: September 13, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Paroxysmal nocturnal hemoglobinuria
Hemoglobin
Anemia
LNP023
Iptacopan
Additional relevant MeSH terms:
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Hemoglobinuria
Hemoglobinuria, Paroxysmal
Proteinuria
Urination Disorders
Urologic Diseases
Urological Manifestations
Anemia, Hemolytic
Anemia
Hematologic Diseases
Myelodysplastic Syndromes
Bone Marrow Diseases