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

• Register: EUCTR
• Last refreshed on: 14 March 2022
• Main ID: EUCTR2015-002674-20-SE
• Date of registration: 02/10/2015
• Prospective Registration: Yes
• Primary sponsor: Alexion Pharmaceuticals, Inc.
• Public 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
• Scientific 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
• Date of first enrolment: 30/11/2015
• Target sample size: 18
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002674-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: yes; Open: yes; Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Finland, France, Germany, Russian Federation, Spain, Sweden, Taiwan, United Kingdom

Contacts

• Name: European Clinical Trial Information
• Affiliation: ALEXION EUROPE SAS

• Name: European Clinical Trial Information
• Affiliation: ALEXION EUROPE SAS

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female patients = 18 years of age
2. PNH diagnosis confirmed by documented high-sensitivity flow cytometry (red blood cells [RBCs] and/or granulocytes)
3. Mean lactate dehydrogenase (LDH) =3 × upper limit of normal, based on 2 measurements from separate blood samples collected at least 1 day apart during screening
4. Willing and able to give written informed consent and comply with the study visit schedule
5. Documented meningococcal vaccination not more than 3 years prior to dosing
6. Female patients who consider themselves postmenopausal must provide evidence at screening of menopause status, based on a combination of amenorrhea for at least 1 year and increased serum follicle-stimulating hormone level (> 30 IU/L) on at least 2 occasions (eg, in the absence of hormone replacement therapy, dietary phytoestrogens) or estradiol concentration < 10 pg/mL.
7. Female patients of childbearing potential must use highly effective contraception as defined below, starting at screening and continuing until at least 6 months after the last dose of ALXN1210.
8. Male patients with a female spouse/partner of childbearing potential or a pregnant or breastfeeding spouse or partner must agree to use barrier contraception (male condom) during the Treatment Period and for at least 6 months after the last dose of ALXN1210. Barrier contraception is required even with documented medical assessment of surgical success of a vasectomy. Female spouses/partners of male patients who are of childbearing potential must use highly effective contraception or acceptable contraception, as defined below, starting at screening and continuing until at least 6 months after the last dose of ALXN1210. Male patients must not donate sperm during the
Screening and Treatment Periods and for at least 6 months after the last dose of ALXN1210.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion criteria:
1. Treatment with a complement inhibitor at any time
2. Platelet count < 30,000/mm3 (30 × 109 /L) at screening
3. Absolute neutrophil count < 500/µL (0.5 × 109 /L) at screening
4. History of bone marrow transplantation
5. History of Neisseria meningitidis infection; history of unexplained, recurrent infection; or infection requiring treatment with systemic antibiotics within the last 90 days prior to dosing on Day 1
6. Female patients who are planning to become pregnant, or are pregnant or breastfeeding


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Paroxysmal Nocturnal Hemoglobinuria (PNH)
MedDRA version: 18.0 Level: LLT Classification code 10055629 Term: Paroxysmal nocturnal hemoglobinuria System Organ Class: 100000004857

Intervention(s)

Product Code: ALXN1210
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ALXN1210
Current Sponsor code: ALXN1210
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Main Objective: To evaluate the efficacy, safety, and tolerability of multiple doses of ALXN1210 administered intravenously (IV) to complement inhibitor treatment-naïve patients with PNH

Primary end point(s): Change in LDH levels from baseline to Day 253

Timepoint(s) of evaluation of this end point: Day 1, 7, 15, 22, 29, 43, 57, 85, 113, 127, 141, 169, 197, 211, 225, 253

Secondary Objective: The secondary objectives of the trial are:
- To characterize the pharmacokinetic (PK) and pharmacodynamic (PD) effects of multiple doses of ALXN1210 administered IV to complement inhibitor treatment-naïve patients with PNH
- To investigate the immunogenicity of ALXN1210 administered IV to complement inhibitor treatment-naïve patients with PNH

Secondary Outcome(s)

Secondary end point(s): Efficacy endpoints:
- Changes in hemolysis-related hematologic parameters
- Changes in clinical manifestations

Safety endpoints:
- Change from baseline in the need for blood transfusions
- Change from baseline in disease-associated biomarkers
- Change from baseline in quality of life
- Change from baseline in major adverse vascular events (MAVEs)

Immunogenicity: Measurement of antidrug antibodies (ADA)

Pharmacokinetic/Pharmacodynamic

Safety

Timepoint(s) of evaluation of this end point: Day 1, 7, 15, 22, 29, 43, 57, 85, 113, 127, 141, 169, 197, 211, 225, 253

Secondary ID(s)

2015-002674-20-DE

ALXN1210-PNH-201

Source(s) of Monetary Support

ALEXION PHARMACEUTICALS INC

Ethics review

Status: Approved
Approval date: 30/11/2015
Contact:

Results

• Results available: Yes
• Date Posted: 08/07/2020
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-002674-20/results