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Trial record 1 of 78 for:    "Paroxysmal Nocturnal Hemoglobinuria"
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Efficacy, Safety, Pharmacokinetics and Pharmacodynamics Study, Assessing Multiple LNP023 Doses in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria

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ClinicalTrials.gov Identifier: NCT03896152
Recruitment Status : Recruiting
First Posted : March 29, 2019
Last Update Posted : July 19, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The main purpose of this study is to evaluate the efficacy of LNP023 in patients with PNH, showing signs of active hemolysis

Condition or disease Intervention/treatment Phase
Paroxysmal Nocturnal Hemoglobinuria Drug: LNP023 Phase 2

Detailed Description:

LNP023 is a novel oral small molecular weight compound, that inhibits alternative complement pathway (AP). Blockade of the AP with oral LNP023 has the potential to prevent both intra - and extravascular hemolysis.

This three-period study includes: a screening phase of up to 8 weeks, a baseline visit, Day 1 (first day that the investigational drug is given), a 4-week treatment period of LNP023 at the first dose in the assigned sequence (Period 1), an 8-week treatment period at the second dose in the assigned sequence (Period 2), an approximately 2 year extension Period 3, followed by a taper down period of 2 weeks and end of study visit and a safety follow up call performed 30 days post end of treatment.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, open label study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Open-label, Efficacy, Safety, Pharmacokinetics and Pharmacodynamics Study, Assessing Multiple LNP023 Doses in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria and Active Hemolysis
Actual Study Start Date : April 5, 2019
Estimated Primary Completion Date : December 27, 2019
Estimated Study Completion Date : November 19, 2021


Arm Intervention/treatment
Experimental: Arm 1
approximately 2 year Treatment with low LNP023 dose
Drug: LNP023
approximately 2 year of Treatment with LNP023

Experimental: Arm 2
approximately 2 year Treatment with higher LNP023 dose
Drug: LNP023
approximately 2 year of Treatment with LNP023




Primary Outcome Measures :
  1. Percentage of patients with reduction of Paroxysmal nocturnal hemoglobinuria (PNH) associated hemolysis. [ Time Frame: 12 weeks ]
    Percentage of patients with 60% reduction in lactate dehydrogenase (LDH) or LDH below upper limit of normal (ULN) at any time up to week 12


Secondary Outcome Measures :
  1. Change in total and free hemoglobin [ Time Frame: 12 weeks ]
    To assess the effect of LNP023 on markers of intravascular and extravascular hemolysis.

  2. Profile of Pharmacokinetics (PK): Area Under the Curve (AUC) [ Time Frame: days: 2,15,16,22,29,36,43,57,71,85,88,92,99 ]
    Profile of Pharmacokinetics (PK): Area Under the Curve (AUC)

  3. Prothrombin time (PT) [ Time Frame: 12 weeks ]
    Effect of LNP023 on markers associated with risk of thrombosis.

  4. Change in total carboxyhemoglobin [ Time Frame: 12 weeks ]
    To assess the effect of LNP023 on markers of intravascular and extravascular hemolysis.

  5. Change in reticulocytes [ Time Frame: 12 weeks ]
    To assess the effect of LNP023 on markers of intravascular and extravascular hemolysis.

  6. Change in C3 fragment deposition [ Time Frame: 12 weeks ]
    To assess the effect of LNP023 on markers of intravascular and extravascular hemolysis.

  7. Change in haptoglobin [ Time Frame: 12 weeks ]
    To assess the effect of LNP023 on markers of intravascular and extravascular hemolysis.

  8. Change in bilirubin [ Time Frame: 12 weeks ]
    To assess the effect of LNP023 on markers of intravascular and extravascular hemolysis.

  9. Change in red blood cell count [ Time Frame: 12 weeks ]
    To assess the effect of LNP023 on markers of intravascular and extravascular hemolysis.

  10. Change in platelet counts [ Time Frame: 12 weeks ]
    To assess the effect of LNP023 on markers of intravascular and extravascular hemolysis.

  11. Change in ferritin [ Time Frame: 12 weeks ]
    To assess the effect of LNP023 on markers of intravascular and extravascular hemolysis.

  12. Change in PNH cells [ Time Frame: 12 weeks ]
    To assess the effect of LNP023 on markers of intravascular and extravascular hemolysis.

  13. Profile of Pharmacokinetics: Maximum plasma concentration (Cmax) [ Time Frame: days: 2,15,16,22,29,36,43,57,71,85,88,92,99 ]
    Profile of Pharmacokinetics: Maximum plasma concentration (Cmax)

  14. Activated partial thromboplastin time (aPTT) [ Time Frame: 12 weeks ]
    Effect of LNP023 on markers associated with risk of thrombosis.

  15. D-dimer [ Time Frame: 12 weeks ]
    Effect of LNP023 on markers associated with risk of thrombosis.

  16. fibrinogen [ Time Frame: 12 weeks ]
    Effect of LNP023 on markers associated with risk of thrombosis.

  17. thrombin clotting time [ Time Frame: 12 weeks ]
    Effect of LNP023 on markers associated with risk of thrombosis.



Information from the National Library of Medicine

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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:

  1. Written informed consent must be obtained before any assessment is performed.
  2. Male and female patients at least 18 years old at baseline.
  3. Diagnosis of active PNH based on documented clone size of ≥10% by RBCs and/or granulocytes, measured by GPI-deficiency on flow cytometry (screening or medical history data acceptable).
  4. LDH values > 1.5 x upper limit of the normal range (ULN) for at least 3 measurements over a maximum of 8 weeks prior to Day 1 (Screening, baseline or medical history data acceptable).
  5. Hemoglobin level < 10.5 g/dL at Baseline.
  6. For Period 3 of the study, patients who as per judgment of Investigator benefit from LNP023 treatment based on reduced hemolytic parameters as compared to Screening and Baseline.
  7. Vaccinations against N. meningitidis, S. pneumoniae and H. influenzae is required at least 4 weeks prior to first dosing with LNP023 (existing vaccinations should provide effective titers at time of LNP023 treatment start). If LNP023 treatment has to start earlier than 4 weeks post vaccination, prophylactic antibiotic treatment must be initiated.
  8. Able to communicate well with the investigator, to understand and comply with the requirements of the study. -

Exclusion Criteria:

  1. Participation in any other investigational drug trial or use of other investigational drugs at the time of enrollment, or within 5 elimination half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations.
  2. Patients treated with eculizumab or any other complement inhibitor less than 3 months prior to study Day 1
  3. Known or suspected hereditary or acquired complement deficiency.
  4. History of currently active primary or secondary immunodeficiency.
  5. History of splenectomy.
  6. History of bone marrow/ hematopoietic stem cell or solid organ transplants (e.g. heart, lung, kidney, liver).
  7. Evidence of malignant disease, or malignancies diagnosed within the previous 5 years.
  8. Patients with laboratory evidence of bone marrow failure (reticulocytes < 60x10E9/L, or platelets < 50x10E9/L or neutrophils < 1x10E9/L) verified both at screening and baseline.
  9. History of recurrent meningitis, history of meningococcal infections despite vaccination, as verified at both screening and baseline.
  10. Presence or suspicion (based on judgment of the investigator) of active infection within 2 weeks prior to first dose of LNP023, or history of severe recurrent bacterial infections.
  11. A positive HIV, Hepatitis B (HBV) or Hepatitis C (HCV) test result at screening.
  12. Patients on immunosuppressive agents such, as but not limited to, cyclosporine, tacrolimus, mycophenolate or mycophenolic acid, cyclophosphamide, methotrexate or IV immunoglobulins, less than 8 weeks prior to first treatment with LNP023, unless on a stable regimen for at least 3 months prior to first LNP023 dose.
  13. Systemic corticosteroids unless on a stable dose for at least 4 weeks before randomization.
  14. Severe concurrent co-morbidities not amenable to active treatment; e.g., patients with severe kidney disease (CKD stage 4, dialysis), advanced cardiac disease (NYHA class IV), severe pulmonary arterial hypertension (WHO class IV), or unstable thrombotic event, as judged by the investigator, both at screening and baseline (unless baseline was skipped).
  15. Any medical condition deemed likely to interfere with the patient's participation in the study, or likely to cause serious adverse events during the study.
  16. History of hypersensitivity to the study treatment or its excipients or to drugs of similar chemical classes.
  17. Female patients who are pregnant or breastfeeding, or intending to conceive during the course of the study.
  18. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 1 week after stopping of investigational drug -

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): NCT03896152


Contacts
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Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals

Locations
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Korea, Republic of
Novartis Investigative Site Recruiting
Seoul, Korea, Republic of, 03080
Novartis Investigative Site Recruiting
Seoul, Korea, Republic of, 06351
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 119228
Taiwan
Novartis Investigative Site Recruiting
Taipei, Taiwan, 10002
Sponsors and Collaborators
Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03896152     History of Changes
Other Study ID Numbers: CLNP023X2204
First Posted: March 29, 2019    Key Record Dates
Last Update Posted: July 19, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Complement, alternative pathway, paroxysmal nocturnal hemoglobinuria, hemolysis
Additional relevant MeSH terms:
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Hemoglobinuria
Hemoglobinuria, Paroxysmal
Proteinuria
Urination Disorders
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Anemia, Hemolytic
Anemia
Hematologic Diseases
Myelodysplastic Syndromes
Bone Marrow Diseases