Phase 2 Safety and Efficacy Study of Zilucoplan (RA101495) to Treat PNH Patients

Phase 2 Multicenter, Open-Label, Uncontrolled Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of RA101495 in Subjects With Paroxysmal Nocturnal Hemoglobinuria

The purpose of the study is to evaluate the safety and efficacy of zilucoplan (RA101495) in patients with Paroxysmal Nocturnal Hemoglobinuria (PNH). There will be two groups of patients in the study: the first group will include patients who have never received eculizumab for treatment of PNH. The second group will include patients who have received treatment with eculizumab for at least 6 months prior to the study. Patients will be treated with RA101495 for 12 weeks.

Study Overview

• Status: Completed
• Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
• Intervention / Treatment: Drug: Zilucoplan (RA101495)

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Parkville, Australia
    • Investigative Site
  • New South Wales
    • Gosford, New South Wales, Australia
      • Investigative Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Investigative Site
• Denmark
  • Copenhagen, Denmark
    • Investigative Site
• Finland
  • Helsinki, Finland
    • Investigative Site
• Germany
  • Essen, Germany
    • Investigative Site
  • Ulm, Germany
    • Investigative Site
• Hungary
  • Budapest, Hungary
    • Investigative Site
• New Zealand
  • Christchurch, New Zealand
    • Investigative Site
  • Hamilton, New Zealand
    • Investigative Site
• United Kingdom
  • Leeds, United Kingdom
    • Investigative Site
  • London, United Kingdom
    • Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of PNH by flow cytometry
• For treatment naive patients: subjects must not have received treatment with eculizumab prior to or during the Screening Period and must have a lactate dehydrogenase (LDH) level ≥2 times the upper limit of normal (xULN) during Screening
• For patients who previously received eculizumab: subjects must have received treatment with eculizumab for at least 6 months prior to Screening

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zilucoplan (RA101495) treatment naive; 0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC (treatment naïve)	Drug: Zilucoplan (RA101495); 0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
Experimental: Zilucoplan (RA101495) previously on eculizumab; 0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC (previously on eculizumab)	Drug: Zilucoplan (RA101495); 0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change-from-baseline in Serum Lactate Dehydrogenase (LDH) Level.	The primary efficacy endpoint is the change-from-baseline in serum LDH levels during this period, defined as the mean LDH values of Weeks 6, 8, 10, and 12 minus the baseline value of LDH.	Through Week 12 of the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes From Baseline in Bilirubin Values	Changes from baseline at each of the scheduled post-baseline time-points	Through Week 12 of the study
Total Hemoglobin	Changes from baseline at each of the scheduled post-baseline time-points	Through Week 12 of the Study
Changes From Baseline in Free Hemoglobin Values	Changes from baseline at each of the scheduled post-baseline time-points	Through Week 12 of the study
Haptoglobin Values	Changes from baseline at each of the scheduled post-baseline time-points	Through Week 12 of the Study
Reticulocyte Values	Changes from baseline at each of the scheduled post-baseline time-points	Through Week 12 of the Study
Hemoglobinuria Values	Changes from baseline at each of the scheduled post-baseline 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.	Through Week 12 of the Study

Collaborators and Investigators

• Sponsor: Ra Pharmaceuticals
• Investigators: Principal Investigator: Dr. Anita Hill, St James' Institute of Oncology

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2017
• Primary Completion (Actual): March 28, 2018
• Study Completion (Actual): March 28, 2018

Study Registration Dates

• First Submitted: March 8, 2017
• First Submitted That Met QC Criteria: March 8, 2017
• First Posted (Actual): March 13, 2017

Study Record Updates

• Last Update Posted (Actual): July 27, 2022
• Last Update Submitted That Met QC Criteria: July 26, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: PNH
• Additional Relevant MeSH Terms: Urologic Diseases; Urological Manifestations; Bone Marrow Diseases; Hematologic Diseases; Urination Disorders; Anemia; Proteinuria; Anemia, Hemolytic; Myelodysplastic Syndromes; Hemoglobinuria; Hemoglobinuria, Paroxysmal
• Other Study ID Numbers: RA101495-01.201; 2016-003522-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No