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

Phase 1

Completed

• Conditions: PNH
• Interventions: Biological: ALXN1210

• Registration Number: NCT02598583
• Lead Sponsor: Alexion Pharmaceuticals, Inc.

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2015-11-02
• Study First Submitted QC: 2015-11-04
• Study First Posted: 2015-11-06
• Study Start: 2015-11-12
• Primary Completion: 2016-07-14
• Results First Submitted: 2017-10-30
• Results First Submitted QC: 2018-01-03
• Results First Posted: 2018-01-30
• Study Completion: 2021-03-11
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-22
• Last Update Posted: 2022-05-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort 1	ALXN1210	Participants were administered ALXN1210 900 mg. In the Extension period participants continued at the same dose and frequency as the Primary Evaluation Period.
Cohort 2	ALXN1210	Participants were administered ALXN1210 1800 mg. In the Extension period participants continued at the same dose and frequency as the Primary Evaluation Period.

Primary Outcome Measures

Name	Time	Method
Percent Change In Lactate Dehydrogenase (LDH) Levels From Baseline To Day 169	Baseline, Day 169	Baseline was defined as the average of all available assessments prior to first ALXN1210 infusion.

Secondary Outcome Measures

Name	Time	Method
Percent Change In Haptoglobin Levels From Baseline To Day 169 And Day 1821	Baseline, Day 169, Day 1821	Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Maximum Observed Serum Concentration (Cmax) At Day 1 And Day 141	Day 1 and Day 141
Cmax/D At Day 1 And Day 141	Day 1 and Day 141
Concentration At The End Of The Dosage Interval (Ctrough) At Day 1 And At Day 141	Day 1 and Day 141
Percent Change In Free Hemoglobin Levels From Baseline To Day 169 And Day 1821	Baseline, Day 169, Day 1821	Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Time To Maximum Observed Serum Concentration (Tmax) At Day 1 And Day 141	Day 1 and Day 141
Percent Change In Chicken Red Blood Cell (cRBC) Hemolysis From Baseline To Day 1709	Baseline, Day 1709
Percent Change In Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clones From Baseline To Day 169 And Day 1933	Baseline, Day 169, Day 1933	Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Percent Change In Free Complement Component 5 (C5) Concentration From Baseline To Day 1709	Baseline, Day 1709
Percent Change In Total C5 Concentration From Baseline To Day 1709	Baseline, Day 1709
Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 169 And Day 1821	Baseline, Day 169, Day 1821	Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Percent Change In D-dimer Levels From Baseline To Day 169 And Day 1821	Baseline, Day 169, Day 1821	Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821	Baseline, Day 169, 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.
Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The Last Quantifiable Concentration (AUCt) At Day 1	Day 1	AUCt reported in hours\*microgram/milliliter (h\*ug/mL).
AUCt/ Dose-normalized (D) At Day 1	Day 1
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
AUCtau/D At Day 141	Day 141
Participants Experiencing Antidrug Antibodies (ADAs)	Day 1821

Trial Locations

Locations (1)

Clinical Trial Site; 🇰🇷 Ulsan, Korea, Republic of