ALXN1830 in Patients with Warm Autoimmune Hemolytic Anemia

• Register: EUCTR
• Last refreshed on: 16 November 2020
• Main ID: EUCTR2019-004055-37-ES
• Date of registration: 10/05/2020
• Prospective Registration: No
• Primary sponsor: Alexion Pharmaceuticals, Inc.
• Public title: ALXN1830 in Patients with Warm Autoimmune Hemolytic Anemia
• Scientific title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Study of ALXN1830 in Patients with Warm Autoimmune Hemolytic Anemia
• Date of first enrolment: 06/05/2020
• Target sample size: 32
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-004055-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, France, Germany, Italy, Korea, Republic of, Netherlands, Russian Federation, Spain, Taiwan, United Kingdom, United States

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. Subject must be at least 18 years of age at the time of signing the informed consent
2. Primary or secondary WAIHA, diagnosed at least 6 weeks prior to Screening
3. Failed or have not tolerated at least one prior WAIHA treatment regimen, for example, corticosteroids, rituximab, azathioprine, cyclophosphamide, cyclosporine, mycophenolate mofetil, danazol, or vincristine
4. Hemoglobin < 10 g/dL and = 6 g/dL
6. Positive direct antiglobulin test (Coombs) (IgG positive who are positive or negative for the presence of complement C3 [C3]) at Screening
7. Evidence of active hemolysis including any one of the below:
a. LDH > upper limit of normal (ULN) or
b. Haptoglobin < lower limit of normal (LLN) or
c. Indirect bilirubin > ULN
8. Total IgG > 500 mg/dL at Screening
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 19
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13

Exclusion criteria:
1. Packed RBC or whole blood transfusions in the 2 weeks prior to Screening
2. History of cold antibody AIHA, cold agglutinin syndrome, mixed type AIHA, or paroxysmal cold hemoglobinuria
3. History of drug-induced or infection-related immune hemolytic anemia
4. Iron, folic acid, or vitamin B12 deficiency
5. History of leukemia, Hodgkin, or non-Hodgkin lymphoma. Exception: low-grade chronic lymphocytic leukemia (CLL) with no enlargement of lymph nodes, spleen, or liver, and normal platelet count as per central lab, not requiring treatment for CLL, no more than 3 years since the diagnosis of CLL and after discussion with the Sponsor’s Medical Monitor.
6. History of solid malignancy other than basal cell or squamous cell carcinoma of the skin, carcinoma-in-situ of the cervix, or other malignancy for which the subject had not been disease-free for at least 5 years
7. Active infection or history of recurrent systemic infections in the 2 years prior to Screening
9. Systemic lupus erythematosus (SLE) or other autoimmune disease that is not stable or not well controlled on current therapy


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

Health Condition(s) or Problem(s) studied

WAIHA
MedDRA version: 20.0 Level: LLT Classification code 10003825 Term: Autoimmune hemolytic anemia System Organ Class: 100000004851

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Code: ALXN1830
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ORILANOLIMAB
CAS Number: 2066544-85-0
Current Sponsor code: ALXN1830
Other descriptive name: SYNT001
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: - Assess the effect of ALXN1830 on the need for transfusions compared to placebo
- Assess the effect of ALXN1830 on quality of life compared to placebo
- Assess the effect on ALXN1830 on anemia compared to placebo
- Assess the effect of ALXN1830 on hemolysis compared to placebo
- Assess the effect of ALXN1830 on corticosteroid usage compared to placebo
- Assess the safety and tolerability of ALXN1830 compared to placebo
- Assess the effect of ALXN1830 on serum total IgG levels compared to placebo

Main Objective: Determine the efficacy of ALXN1830 compared to placebo in adult subjects with WAIHA

Primary end point(s): Proportion of subjects achieving a = 2 g/dL increase in Hgb, without requiring increase in any WAIHA medication after Day 1 and without pRBC transfusions after Day 14.

Timepoint(s) of evaluation of this end point: From baseline (Day 1) to Day 92 (after 13 weeks of treatment)

Secondary Outcome(s)

Secondary end point(s): - Total number of units of pRBCs transfused from Day 15 to Day 92
- Change in quality of life (QoL) assessed via EQ-5D-5L and Functional Assessment of Cancer Therapy Anemia (FACT-AN) from baseline to Day 92
- Durability: number of weekly Hgb measurements = 2 g/dL over baseline
- Proportion of subjects who require new WAIHA rescue medication or increase in the dose of an existing WAIHA medication or pRBC transfusions (Day 15 to Day 92) for the treatment of anemia
- Markers of hemolysis: absolute and percentage change from baseline to Day 92 in serum lactate dehydrogenase (LDH) levels, absolute reticulocyte count, serum indirect bilirubin, serum haptoglobin
- Total corticosteroid use from Day 1 to Day 92
- Safety and tolerability of ALXN1830 compared to placebo assessed by physical examinations, vital signs, ECGs, laboratory assessments, and incidence of AEs, SAEs and AESIs
- Serum concentration of ALXN1830 over time
- Mean and percentage decrease in serum total IgG levels by dose group (ALXN1830 vs placebo) and time point

Timepoint(s) of evaluation of this end point: The timepoint(s) is precised for each secondary end point at E.5.2

Secondary ID(s)

ALXN1830-WAI-201

Source(s) of Monetary Support

Alexion Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 22/04/2020
Contact: