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)

• ClinicalTrials.gov Identifier: NCT03226678
• Recruitment Status: Completed
• First Posted: July 24, 2017
• Last Update Posted: April 3, 2023
• Sponsor: Apellis Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Apellis Pharmaceuticals, Inc.

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Warm Autoimmune Hemolytic Anemia; Cold Agglutinin Disease	Drug: APL-2	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: August 31, 2017
• Actual Primary Completion Date: September 12, 2022
• Actual Study Completion Date: September 12, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Total Number of AEs [ Time Frame: Baseline to week 48 ]
   The primary safety endpoints of the study are the incidence and severity of treatment emergent adverse events (TEAEs) following administration of multiple doses of subcutaneous (SC) APL-2.
2. Change from baseline in hemoglobin [ Time Frame: Baseline to week 48 ]
   Efficacy endpoint assessment.
3. APL-2 serum concentrations and pharmacokinetic (PK) parameters [ Time Frame: Baseline to week 48 ]
   APL-2 serum concentrations and pharmacokinetic (PK) parameter (Cmax)

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

American Institute of Research

Whittier, California, United States, 90603

United States, Florida

Lakes Research

Miami Lakes, Florida, United States, 33014

Mid Florida Hematology Oncology

Orange City, Florida, United States, 32763

United States, Iowa

University of Iowa Hospitals

Iowa City, Iowa, United States, 52242

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, North Carolina

East Carolina University

Greenville, North Carolina, United States, 27834

United States, Tennessee

University of Tennessee Medical Center

Knoxville, Tennessee, United States, 37920

United States, Washington

Northwest Medical Specialties

Tacoma, Washington, United States, 98405

Sponsors and Collaborators

Apellis Pharmaceuticals, Inc.

More Information

• Responsible Party: Apellis Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03226678
• Other Study ID Numbers: APL2-CP-AIHA-208
• First Posted: July 24, 2017
• Last Update Posted: April 3, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Anemia; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Hemolysis; Hematologic Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases