Phase 2 Safety and Efficacy Study of Zilucoplan (RA101495) to Treat PNH Patients Who Have an Inadequate Response to Eculizumab

A Phase 2 Multicenter, Open-Label, Uncontrolled Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of RA101495 in Subjects With Paroxysmal Nocturnal Hemoglobinuria Who Have an Inadequate Response to Eculizumab

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03030183

Enrollment

Registered

2017-01-24

Start date

2017-04-17

Completion date

2018-03-28

Last updated

2022-07-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Keywords

PNH

Brief summary

The purpose of the study is to evaluate the safety and efficacy of RA101495 in patients with paroxysmal nocturnal hemoglobinuria (PNH) who have an inadequate response to eculizumab. Patients will be treated with RA101495 for 12 weeks.

Interventions

DRUGZilucoplan (RA101495)

0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Diagnosis of PNH by flow cytometry * Inadequate response to eculizumab defined as having received eculizumab for at least 6 months plus a documented LDH level ≥ 1.5 x the upper limit of normal (ULN) and/or the presence of a known C5 mutation conferring resistance to eculizumab

Exclusion criteria

* History of meningococcal disease * Current systemic infection or suspicion of active bacterial infection

Design outcomes

Primary

Measure	Time frame	Description
Change-from-baseline in Serum Lactate Dehydrogenase (LDH) Levels.	Through Week 12 of the study	Change-from-baseline through Week 12 in serum lactate dehydrogenase (LDH) levels

Secondary

Measure	Time frame	Description
Change-from-baseline Total Hemoglobin Values	Through week 12	Changes from baseline at each of the scheduled postbaseline time-points
Change-from-baseline Free Hemoglobin Values	Through week 12	Changes from baseline at each of the scheduled postbaseline time-points
Change-from-baseline Bilirubin Values	Through week 12	Changes from baseline at each of the scheduled postbaseline time-points
Change-from-baseline Reticulocyte Values	Through week 12	Changes from baseline at each of the scheduled postbaseline time-points
Change-from-baseline Hemoglobinuria Values	Through week 12	Changes from baseline at each of the scheduled postbaseline time-points Hemoglobinuria was assessed using a urine colorimetric scoring system with a score of 1 through 10. Where 1 represents no hemoglobinuria and 10 represents maximum hemoglobinuria.
Change-from-baseline Haptoglobin Values	Through week 12	Changes from baseline at each of the scheduled postbaseline time-points

Countries

United States

Participant flow

Participants by arm

Arm	Count
Zilucoplan (RA101495) Subjects will receive zilucoplan (RA101495) at the dose of 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC Zilucoplan (RA101495): 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC	3
Total	3

Baseline characteristics

Characteristic	Zilucoplan (RA101495)
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	3 Participants
Age, Continuous	35.3 years STANDARD_DEVIATION 16.3
BMI	35.72 kg/m2 STANDARD_DEVIATION 7.76
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Height	176.20 cm STANDARD_DEVIATION 7.6
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	1 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) White	1 Participants
Region of Enrollment United States	3 participants
Sex: Female, Male Female	1 Participants
Sex: Female, Male Male	2 Participants
Weight	109.67 kg STANDARD_DEVIATION 13.97

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 3
other Total, other adverse events	3 / 3
serious Total, serious adverse events	0 / 3

Outcome results

Primary