Clinical study to assess the safety, tolerability, efficacy and pharmacokinetics of APL-2 in patients with Warm Antibody Autoimmune Hemolytic Anemia (wAIHA) or Cold Agglutinin Disease (CAD)
- Conditions
- Patients affected by Warm Antibody Autoimmune Hemolytic Anemia (wAIHA) or Cold Agglutinin Disease (CAD)MedDRA version: 20.0Level: LLTClassification code 10002045Term: Anaemia haemolyticSystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2017-003363-35-IT
- Lead Sponsor
- APELLIS PHARMACEUTCIALS, INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 12
1.At least 18 years of age
2.Weight < 125 Kg
3.Subjects must have a primary diagnosis of wAIHA or CAD defined by the presence of hemolytic anemia and positive DAT for wAIHA (IgG) or CAD (C3)
4.Hemoglobin <11 g/dL
5.Clinical symptoms of hemolysis with abnormal values by any of the hemolytic markers:
a.Increased absolute reticulocyte count (above ULN);
b.Reduced haptoglobin (below LLN);
c.Increased lactase dehydrogenase (LDH) (above ULN);
d.Increased indirect bilirubin (above ULN)
6.Women of child-bearing potential (WOCBP) (defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause)m ust have a negative pregnancy test at screening and must agree to use protocol defined methods of contraception for the duration of the study and 60 days after their last dose of study drug
7.Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study and 60 days after their last dose of study drug
8.Able to provide documentary evidence of Neisseria meningitides types A, C, W, Y and B (administered as two separate vaccinations), Pneumococcal conjugate vaccine or Pneumococcal polysaccharide vaccine 23 (PCV13 or PPSV23, respectively) and
Haemophilus influenzae Type B (Hib) vaccination within 2 years prior to Day -14, OR willing to receive vaccinations against Neisseria meningitides at least two weeks prior to dosing on Day 1 with a booster after Day 56 (for both vaccinations) and Pneumococcal and Hib vaccines prior to dosing on Day 1
9.Willing and able to give informed consent
10.Specific for wAIHA: Relapsed from, did not respond or relapsed, or did not tolerate, at least one prior wAIHA treatment regimen (such as prednisone, rituximab).
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 8
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4
1.Prior treatment with rituximab within 90 days
2.Deficiency of iron, folic acid and vitamin B12 prior to treatment phase
3.Abnormal liver function as indicated by a direct bilirubin above normal level, and/or an AST or ALT level > 2x upper limit of normal. Elevated indirect bilirubin due to hemolysis is not an exclusion criteria
4.Creatinine clearance (CrCl) <60 mL/min (Cockcroft-Gault formula) at screening
5.Active aggressive lymphoma requiring therapy or an active non-lymphatic malignant disease other than basal cell carcinoma or CIS of the cervix
6.Presence or suspicion of active bacterial or viral infection, in the opinion of the Investigator, at screening or severe recurrent bacterial infections
7.Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days prior to screening period
8.Pregnant, breast-feeding, or intending to conceive during the course of the study, including the Post-Treatment Phase
9.Inability to cooperate or any condition that, in the opinion of the investigator, could increase the subject's risk by participating in the study or confound the outcome of the study
10.Myocardial infarction, CABG, coronary or cerebral artery stenting and /or angioplasty,stroke, cardiac surgery, or hospitalization for congestive heart failure within 3 months or > Class 2 Angina Pectoris or NYHA Heart Failure Class >2
11.QTcF > 470 ms
12.PR > 280 ms
13.Mobitz II 2nd degree AV Block, 2:1 AV Block, High Grade AV Block, or Complete Heart Block unless the patient has an implanted pacemaker or implantable cardiac defibrillator (ICD) with backup pacing capabilities.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the safety, tolerability, preliminary efficacy and PK of multiple SC doses of APL-2 in subjects with Warm Antibody Autoimmune Hemolytic Anemia (wAIHA) or Cold Agglutinin Disease (CAD).;Secondary Objective: Exploratory objective: to evaluate the PD of multiple SC doses of APL-2 when administered to patients with Autoimmune Hemolytic Anemia (AIHA).;Primary end point(s): Incidence and severity of treatment emergent adverse events (TEAEs) following administration of multiple doses of subcutaneous (SC) APL-2.;Timepoint(s) of evaluation of this end point: This endpoint will be assessed at months 2, 3, 6, and 12.
- Secondary Outcome Measures
Name Time Method