Study to Assess the Safety, Tolerability, Efficacy and PK of APL-2 in Patients With Warm Type Autoimmune Hemolytic Anemia (wAIHA) or Cold Agglutinin Disease (CAD)

An Open Label, Prospective, Study to Assess the Safety, Tolerability, Efficacy and Pharmacokinetics of APL-2 in Patients With Warm Type Autoimmune Hemolytic Anemia (wAIHA) or Cold Agglutinin Disease (CAD)

This study is to assess the safety, tolerability, preliminary efficacy, and pharmacokinetics of APL-2 in subjects with warm Autoimmune Hemolytic Anemia (wAIHA) or Cold Agglutinin Disease (CAD).

Study Overview

• Status: Completed
• Conditions: Cold Agglutinin Disease; Warm Autoimmune Hemolytic Anemia
• Intervention / Treatment: Drug: APL-2

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Whittier, California, United States, 90603
      • American Institute of Research
  • Florida
    • Miami Lakes, Florida, United States, 33014
      • Lakes Research
    • Orange City, Florida, United States, 32763
      • Mid Florida Hematology Oncology
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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. Signs of hemolysis with abnormal values by any of the hemolytic markers:

   1. Increased absolute reticulocyte count (above ULN)
   2. Reduced haptoglobin (below LLN)
   3. Increased lactase dehydrogenase (LDH) (above ULN)
   4. 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) must 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 the following vaccinations within 2 years prior to screening:

   1. Neisseria meningitides types A, C, W, Y and type B (administered as two separate vaccinations)
   2. Streptococcus pneumoniae (Pneumococcal conjugate vaccine and Pneumococcal polysaccharide vaccine 23 [PCV13 and/or PPSV23, respectively])
   3. Haemophilus influenzae Type B (Hib) vaccine

   Subjects that do not have documentary evidence must be willing to receive any missing vaccinations as outlined below:

   1. Neisseria meningitides types A, C, W, Y and type B must be administered prior to dosing on Day 1. A booster is administered after at least 8 weeks (Day 56; for both vaccinations).
   2. Streptococcus pneumoniae PCV13 must be administered prior to dosing on Day 1 (see Section 12.2 for details). A PPSV23 booster is administered after at least 8 weeks (Day 56)
   3. Haemophilus influenze Type B (Hib) must be administered 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).

Exclusion Criteria:

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. Please note elevated indirect bilirubin due to hemolysis is not an exclusion criteria.
4. Elevated bilirubin not due to active hemolysis. Any elevation of bilirubin >ULN will require Sponsor review and approval for subject enrollment into the trial.
5. Active aggressive lymphoma requiring therapy or an active non-lymphatic malignant disease other than basal cell carcinoma or carcinoma in situ (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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 270mg or 360mg APL-2 administered subcutaneously daily (CAD)	Drug: APL-2; Complement (C3) Inhibitor
Experimental: 270mg or 360mg APL-2 administered subcutaneously daily (wAIHA)	Drug: APL-2; Complement (C3) Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity	TEAEs were defined as adverse events (AEs) that occurred after dosing on Day 1 and up to 56 days after the last dose of study drug. A treatment-related TEAE is defined as a TEAE with a relationship to study drug of probably, possibly, unlikely, or unrelated. A serious adverse event (SAE) is defined as any AE that resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant incapacity or substantial disruption of ability to conduct normal life functions; was a congenital anomaly or birth defect. TEAEs were graded according to Common Terminology Criteria for Adverse Events v4.03 based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.	Part A:From first dose of study drug (Part A Day 1) up to 30days after last dose of study drug in Part A,approximately 366days Part B:From first dose of study drug (Part B Day 1) up to 56days after last dose of study drug in Part B,approximately 980days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Hemoglobin at Weeks 48 and 132	Hematology assessments of hemoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Mean change from baseline in hemoglobin results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups.	Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132
Number of Subjects Who Received Red Blood Cell (RBC) Transfusions	The number of on-study RBC transfusions were monitored throughout the treatment period.	From Day 1 up to Week 132
Mean Change From Baseline in Absolute Reticulocyte Count (ARC) at Weeks 48 and 132	Hematology assessments of ARC were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Mean change from baseline in ARC results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups.	Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132
Mean Change From Baseline in Lactate Dehydrogenase (LDH) at Weeks 48 and 132	Serum chemistry assessments of LDH were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Mean change from baseline in LDH results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups.	Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132
Mean Change From Baseline in Haptoglobin at Weeks 48 and 132	Serum chemistry assessments of haptoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Mean change from baseline in haptoglobin results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups.	Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132
Mean Change From Baseline in Indirect Bilirubin at Weeks 48 and 132	Serum chemistry assessments of indirect bilirubin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Mean change from baseline in indirect bilirubin results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups.	Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132
Maximum Observed Trough Serum Concentration (Ctrough,Max) of Pegcetacoplan	Blood samples were collected for the assessment of Ctrough,max of pegcetacoplan.	Pre-dose and 4 hours postdose on Day 1; pre-dose on Weeks 1, 2, 4, 8, 12, 16, 20, 24, 32, 36, 40, 48, 60, 72, 84, 96, 108, 120 and 132
Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Weeks 48 and 132	The FACIT-Fatigue Scale is a 13 item Likert scaled instrument where the subject was presented with 13 statements and asked to indicate their response as it applied to the past 7 days. The 5 possible responses were 'Not at all' (0), 'A little bit (1), 'Somewhat' (2), 'Quite a bit' (3) and 'Very much' (4). There are 13 statements with the total score ranging from 0 to 52 and higher scores indicating better quality of life. Mean change from baseline in FACIT-Fatigue score results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups.	Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132
Mean Change From Baseline in Linear Analog Scale Assessment (LASA) Score at Weeks 48 and 132	The LASA consists of 5 single statements asking subjects to rate their perceived level of functioning. Specific domains include physical well-being (fatigue, activity level), emotional well-being (depression, anxiety, stress), spiritual well-being (sense of meaning), and intellectual well-being (ability to think clearly and concentrate). An item for overall quality of life is also included. Each domain scale range from 0 to 10. Where, 0 = as bad as it can be and 10 = as good as it can be. The total score ranging from 0 to 50 and higher scores indicating better quality of life. Mean change from baseline in LASA score results were summarized from Part A baseline for Part A reporting groups and from Part B baseline for Part B reporting groups.	Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132

Collaborators and Investigators

• Sponsor: Apellis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2017
• Primary Completion (Actual): September 12, 2022
• Study Completion (Actual): September 12, 2022

Study Registration Dates

• First Submitted: July 7, 2017
• First Submitted That Met QC Criteria: July 19, 2017
• First Posted (Actual): July 24, 2017

Study Record Updates

• Last Update Posted (Actual): December 12, 2024
• Last Update Submitted That Met QC Criteria: November 19, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Hematologic Diseases; Anemia; Hemolysis; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune
• Other Study ID Numbers: APL2-CP-AIHA-208

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No