Open-label, Multiple Ascending Dose Study of Ravulizumab (ALXN1210) in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Paroxysmal Nocturnal Hemoglobinuria Clinical Trial

Official title:

A Phase 2, Open-label, Multiple Ascending Dose Study to Evaluate the Efficacy, Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of ALXN1210 Administered Intravenously to Patients With Paroxysmal Nocturnal Hemoglobinuria

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02605993
• Other study ID #: ALXN1210-PNH-201
• Secondary ID: 2015-002674-20
• Status: Completed
• Phase: Phase 2
• Start date: January 4, 2016
• Est. completion date: January 12, 2022

Study information

• Verified date: December 2022
• Source: Alexion Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of this study is to evaluate the safety, tolerability, and efficacy of multiple intravenous (IV) doses of ravulizumab administered to complement inhibitor treatment-naïve participants with PNH.

Description:

The study consisted of a screening period of up to 30 days and a Treatment Period of up to 253 days for Cohorts 1-3 and 281 days for Cohort 4. After completion of the Treatment Period, all participants had the opportunity to enter the Extension Period, wherein participants continue to receive ravulizumab for up to 5 years. The first dose in the Extension Period occurred on Day 253 for Cohorts 1-3 and on Day 281 for Cohort 4. The data presented includes the Primary Completion date of the study for the Treatment Period. The results for the Extension Period will be reported after study completion.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: January 12, 2022
• Est. primary completion date: February 23, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female =18 years of age

2. PNH diagnosis confirmed by documented high-sensitivity flow cytometry

3. Documented meningococcal vaccination not more than 3 years prior to dosing

4. Female participants of childbearing potential were to use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.

5. Willing and able to give written informed consent and comply with the study visit schedule

Exclusion Criteria:

1. Treatment with a complement inhibitor at any time

2. Female participants who are planning to become pregnant, or are pregnant, breastfeeding or who had a positive pregnancy test at screening or Day 1

3. Participation in an interventional clinical study within 30 days before initiation of dosing on Day 1, or use of any experimental therapy within 30 days prior to dosing on Day 1, or within 5 half-lives of the investigational product, whichever was greater

4. History of allergy to any drug, allergen, excipients of ravulizumab or known allergy to Chinese hamster ovary cell proteins

5. Inability to comply with study requirements

6. History of any clinically significant cardiac, hepatic, immunologic, pulmonary, or rheumatoid disease that, in the Investigator's judgment, would preclude participation

7. Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the participant unsuitable for enrollment

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Paroxysmal Nocturnal Hemoglobinuria
• PNH

Intervention

Biological:
• Ravulizumab
All treatments were given as IV infusions.

Locations

Country	Name	City	State
Canada	Clinical Trial Site	Toronto	Ontario
France	Clinical Trial Site	Lille
France	Clinical Trial Site	Lyon	Pierre-Bénite
France	Clinical Trial Site	Paris
Germany	Clinical Trial Site	Aachen	Nordrhein Westfalen
Germany	Clinical Trial Site	Essen	Nordrhein Westfalen
Germany	Clinical Trial Site	Ulm	Baden Wuerttemberg
Korea, Republic of	Clinical Trial Site	Seoul
Korea, Republic of	Clinical Trial Site	Seoul
Spain	Clinical Trial Site	Badalona	Barcelona
Spain	Clinical Trial Site	Barcelona
Spain	Clinical Trial Site	Madrid
Spain	Clinical Trial Site	Majadahonda	Madrid
Taiwan	Clinical Trial Site	Taipei City
United Kingdom	Clinical Trial Site	Leeds	West Yorkshire
United Kingdom	Clinical Trial Site	London

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals

Countries where clinical trial is conducted

Canada,  France,  Germany,  Korea, Republic of,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change In LDH Levels From Baseline To Day 253 And Day 281	The percent change in LDH levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.	Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
Secondary	Percent Change In Free Hemoglobin Levels From Baseline To Day 253 And Day 281	The percent change in free hemoglobin levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.	Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
Secondary	Percent Change In Haptoglobin Levels From Baseline To Day 253 And Day 281	The percent change in haptoglobin levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.	Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
Secondary	Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 253 And Day 281	The percent change in reticulocyte/erythrocyte count levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.	Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
Secondary	Percent Change In PNH RBC Types II And III Clone Size From Baseline To Day 253	The percent change in paroxysmal nocturnal hemoglobinuria (PNH) red blood cell (RBC), summed types II and III, clone size levels were assessed from Baseline to Day 253 for Cohorts 1 to 4.	Baseline, Day 253 (Cohorts 1 to 4)
Secondary	Percent Change In D-dimer From Baseline To Day 253 And Day 281	The percent change in D-dimer levels were assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.	Baseline to Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)
Secondary	Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281	Clinical manifestations were assessed from Baseline to Day 253 for Cohorts 1 to 3 and from Baseline to Day 281 for Cohort 4 only. Clinical manifestations were defined as fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction (male participants only). Improvement was defined as present at Baseline and absent at Day endpoint. Worsening was defined as absent at Baseline and present at Day endpoint. No Change was defined as no change from Baseline and time point of endpoint.	Baseline, Day 253 (Cohorts 1 to 3) and Day 281 (Cohort 4)