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Proof of Concept Study to Assess the Efficacy, Safety and Pharmacokinetics of LFG316 in Patients With Paroxysmal Nocturnal Hemoglobinuria

Primary Purpose

Paroxysmal Nocturnal Hemoglobinuria PNH

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

LFG316

LNP023

About this trial

This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria PNH focused on measuring PNH, LFG316, LNP023

Eligibility Criteria

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

Inclusion Criteria:

Male and female patients between the age of 18-75 (inclusive), or 18-65 (applicable in Czech Republic) with a diagnosis of PNH prior to screening
A documented PNH clone size of ≥10% by RBCs and/or granulocytes
Serum LDH levels at least 1.5-fold above the upper limit of normal (ULN) at screening
Negative pregnancy test for women of child bearing potential at screening
Previous vaccination against Neisseria meningitidis is required at least 2 weeks prior to first dosing.

Exclusion Criteria:

Known or suspected hereditary complement deficiency
History of recurrent meningitis, history of meningococcal meningitis despite vaccination
Presence or suspicion (based on judgment of the investigator) of active bacterial infection within 2 weeks prior to first dose of LFG316, or recurrent bacterial infections
Under active therapy with other agents interfering with the complement system
Severe concurrent co-morbidities that are a likely caused by underlying autoimmune diseases other than PNH
Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 50 days after the last dose of LFG316.

Sites / Locations

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

LFG316 then LNP023

Arm Description

LFG316: Treatment periods 1-3 and first 4 weeks of period 4. LNP023: Treatment Period 4

Outcomes

Primary Outcome Measures

Serum lactate dehydrogenase (LDH) levels

Changes in serum lactate dehydrogenase (LDH) levels after treatment with LFG316

Secondary Outcome Measures

Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Including any clinically relevant findings related with ECG, vital signs, laboratory data after treatment with LFG316

AUC (0-t) = Area under the serum concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t) - Pharmacokinetics parameter

Blood draw for pharmacokinetics evaluation after treatment with LFG316

Maximum Plasma Concentration (Cmax) - Pharmacokinetics parameter

Blood draw for pharmacokinetics evaluation after treatment with LFG316

Time to Maximum Concentration (Tmax) - Pharmacokinetics parameter

Blood draw for pharmacokinetics evaluation after treatment with LFG316

Full Information

NCT ID

NCT02534909

First Posted

August 7, 2015

Last Updated

January 24, 2023

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02534909

Brief Title

Proof of Concept Study to Assess the Efficacy, Safety and Pharmacokinetics of LFG316 in Patients With Paroxysmal Nocturnal Hemoglobinuria

Official Title

An Open-label Proof of Concept Study to Assess the Efficacy, Safety and Pharmacokinetics of LFG316, an Anti-C5 Monoclonal Antibody in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Completed

Study Start Date

September 9, 2015 (Actual)

Primary Completion Date

May 24, 2022 (Actual)

Study Completion Date

May 24, 2022 (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

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

To determine whether LFG316 can induce a hematological response, as measured by reduction in hemolytic activity, in patients with PNH.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Paroxysmal Nocturnal Hemoglobinuria PNH

Keywords

PNH, LFG316, LNP023

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

LFG316 then LNP023

Arm Type

Experimental

Arm Description

LFG316: Treatment periods 1-3 and first 4 weeks of period 4. LNP023: Treatment Period 4

Intervention Type

Biological

Intervention Name(s)

LFG316

Other Intervention Name(s)

LFG316 then LNP023

Intervention Description

LFG316 will be administered to all patients enrolled in the study LFG316: Treatment periods 1-3 and first 4 weeks of period 4. LNP023: Treatment Period 4

Intervention Type

Drug

Intervention Name(s)

LNP023

Other Intervention Name(s)

LFG316 then LNP023

Intervention Description

LNP023 will be administered in period 4 to patients who participate in period 3 of this study and are willing to join long term extension study with LNP023.

Primary Outcome Measure Information:

Title

Serum lactate dehydrogenase (LDH) levels

Description

Changes in serum lactate dehydrogenase (LDH) levels after treatment with LFG316

Time Frame

Screening, weekly for 4 weeks, every 2 weeks from week 4 to week 208, every 8 weeks from week 210 to 312 in periods 1-3, every 1 or 2 weeks from day 1 to day 57, every 4 or 8 weeks from day 85 to day 141 in period 4, and EoS

Secondary Outcome Measure Information:

Title

Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Description

Including any clinically relevant findings related with ECG, vital signs, laboratory data after treatment with LFG316

Time Frame

Participants will be monitored for AEs and SAEs for the whole duration of the study (i.e. up to 312 weeks after the first treatment for periods 1-3 and up to day 148 for period 4)

Title

AUC (0-t) = Area under the serum concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t) - Pharmacokinetics parameter

Description

Blood draw for pharmacokinetics evaluation after treatment with LFG316

Time Frame

320 weeks: screening visit, weekly visits for 4 weeks, and every 4 weeks from week 4 to week 54, visit on weeks 80, 106 132, 158, 184 and EOS)

Title

Maximum Plasma Concentration (Cmax) - Pharmacokinetics parameter

Description

Blood draw for pharmacokinetics evaluation after treatment with LFG316

Time Frame

320 weeks: screening visit, weekly visits for 4 weeks, and every 4 weeks from week 4 to week 54, visit on weeks 80, 106 132, 158, 184 and EOS)

Title

Time to Maximum Concentration (Tmax) - Pharmacokinetics parameter

Description

Blood draw for pharmacokinetics evaluation after treatment with LFG316

Time Frame

320 weeks: screening visit, weekly visits for 4 weeks, and every 4 weeks from week 4 to week 54, visit on weeks 80, 106 132, 158, 184 and EOS)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male and female patients between the age of 18-75 (inclusive), or 18-65 (applicable in Czech Republic) with a diagnosis of PNH prior to screening A documented PNH clone size of ≥10% by RBCs and/or granulocytes Serum LDH levels at least 1.5-fold above the upper limit of normal (ULN) at screening Negative pregnancy test for women of child bearing potential at screening Previous vaccination against Neisseria meningitidis is required at least 2 weeks prior to first dosing. Exclusion Criteria: Known or suspected hereditary complement deficiency History of recurrent meningitis, history of meningococcal meningitis despite vaccination Presence or suspicion (based on judgment of the investigator) of active bacterial infection within 2 weeks prior to first dose of LFG316, or recurrent bacterial infections Under active therapy with other agents interfering with the complement system Severe concurrent co-morbidities that are a likely caused by underlying autoimmune diseases other than PNH Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 50 days after the last dose of LFG316.

Facility Information:

Facility Name

Novartis Investigative Site

City

Brno Bohunice

State/Province

Czech Republic

ZIP/Postal Code

625 00

Country

Czechia

Facility Name

Novartis Investigative Site

City

Fukushima city

State/Province

Fukushima

ZIP/Postal Code

960 1295

Country

Japan

Facility Name

Novartis Investigative Site

City

Isehara

State/Province

Kanagawa

ZIP/Postal Code

259-1193

Country

Japan

Facility Name

Novartis Investigative Site

City

Suita

State/Province

Osaka

ZIP/Postal Code

565 0871

Country

Japan

Facility Name

Novartis Investigative Site

City

Shinjuku-ku

State/Province

Tokyo

ZIP/Postal Code

160-0023

Country

Japan

Facility Name

Novartis Investigative Site

City

Niigata

ZIP/Postal Code

951 8520

Country

Japan

Facility Name

Novartis Investigative Site

City

Vilnius

ZIP/Postal Code

LT-08661

Country

Lithuania

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

Proof of Concept Study to Assess the Efficacy, Safety and Pharmacokinetics of LFG316 in Patients With Paroxysmal Nocturnal Hemoglobinuria

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