Dose-Escalation Study of ALXN1210 IV in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)

PNH Clinical Trial

Official title:

An Open-Label, Intrapatient, Dose-Escalation Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of ALXN1210 Administered Intravenously to Patients With Paroxysmal Nocturnal Hemoglobinuria

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02598583
• Other study ID #: ALXN1210-PNH-103
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 12, 2015
• Est. completion date: March 11, 2021

Study information

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

Clinical Trial Summary

This study evaluated the safety, tolerability, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of multiple intravenous (IV) doses of ALXN1210 administered to participants with PNH who have not previously been treated with complement inhibitor.

Description:

The data presented is up to the Primary Completion date of the study and is for the 24-week Primary Evaluation period. The study also includes an Extension Period of up to 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: March 11, 2021
• Est. primary completion date: July 14, 2016
• 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 used highly effective contraception starting at screening and continuing until at least 24-weeks after the last dose of ALXN1210

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. Females who were 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 product, whichever is greater

4. History of allergy to excipients of ALXN1210 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, made the participant unsuitable for enrollment

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• PNH

Intervention

Biological:
• ALXN1210
Participants were administered ravulizumab as an IV infusion every 4 weeks.

Locations

Country	Name	City	State
Australia	Clinical Trial Site	Liverpool	New South Wales
Australia	Clinical Trial Site	Woolloongabba	Queensland
Korea, Republic of	Clinical Trial Site	Seoul
Korea, Republic of	Clinical Trial Site	Seoul
Korea, Republic of	Clinical Trial Site	Seoul
Korea, Republic of	Clinical Trial Site	Seoul
Korea, Republic of	Clinical Trial Site	Seoul
Korea, Republic of	Clinical Trial Site	Ulsan

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals

Countries where clinical trial is conducted

Australia,  Korea, Republic of, 

References & Publications (1)

Röth A, Rottinghaus ST, Hill A, Bachman ES, Kim JS, Schrezenmeier H, Terriou L, Urbano-Ispizua Á, Wells RA, Jang JH, Kulasekararaj AG, Szer J, Aguzzi R, Damokosh AI, Shafner L, Lee JW. Ravulizumab (ALXN1210) in patients with paroxysmal nocturnal hemoglobinuria: results of 2 phase 1b/2 studies. Blood Adv. 2018 Sep 11;2(17):2176-2185. doi: 10.1182/bloodadvances.2018020644. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change In Lactate Dehydrogenase (LDH) Levels From Baseline To Day 169	Baseline was defined as the average of all available assessments prior to first ALXN1210 infusion.	Baseline, Day 169
Secondary	Percent Change In Free Hemoglobin Levels From Baseline To Day 169 And Day 1821	Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.	Baseline, Day 169, Day 1821
Secondary	Percent Change In Haptoglobin Levels From Baseline To Day 169 And Day 1821	Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.	Baseline, Day 169, Day 1821
Secondary	Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 169 And Day 1821	Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.	Baseline, Day 169, Day 1821
Secondary	Percent Change In Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clones From Baseline To Day 169 And Day 1933	Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.	Baseline, Day 169, Day 1933
Secondary	Percent Change In D-dimer Levels From Baseline To Day 169 And Day 1821	Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.	Baseline, Day 169, Day 1821
Secondary	Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821	Clinical manifestations are defined as fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction (ED) by cohort. Improvement is defined as present at baseline and absent at Day 169 endpoint. Worsening is defined as absent at Baseline and present at Day 169 endpoint.	Baseline, Day 169, Day 1821
Secondary	Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The Last Quantifiable Concentration (AUCt) At Day 1	AUCt reported in hours*microgram/milliliter (h*ug/mL).	Day 1
Secondary	AUCt/ Dose-normalized (D) At Day 1		Day 1
Secondary	Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The End Of The Dosing Interval (AUCtau) At Day 141		Day 141
Secondary	AUCtau/D At Day 141		Day 141
Secondary	Maximum Observed Serum Concentration (Cmax) At Day 1 And Day 141		Day 1 and Day 141
Secondary	Cmax/D At Day 1 And Day 141		Day 1 and Day 141
Secondary	Concentration At The End Of The Dosage Interval (Ctrough) At Day 1 And At Day 141		Day 1 and Day 141
Secondary	Time To Maximum Observed Serum Concentration (Tmax) At Day 1 And Day 141		Day 1 and Day 141
Secondary	Percent Change In Chicken Red Blood Cell (cRBC) Hemolysis From Baseline To Day 1709		Baseline, Day 1709
Secondary	Percent Change In Free Complement Component 5 (C5) Concentration From Baseline To Day 1709		Baseline, Day 1709
Secondary	Percent Change In Total C5 Concentration From Baseline To Day 1709		Baseline, Day 1709
Secondary	Participants Experiencing Antidrug Antibodies (ADAs)		Day 1821

External Links

•   Ravulizumab (ALXN1210) in patients with paroxysmal nocturnal hemoglobinuria: results of 2 phase 1b/2 studies