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)

NCT03226678 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: APL2-CP-AIHA-208
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 8

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).

Conditions

Warm Autoimmune Hemolytic Anemia; Cold Agglutinin Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Mean Change From Baseline in Hemoglobin at Weeks 48 and 132

  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

  From Day 1 up to Week 132

• Mean Change From Baseline in Absolute Reticulocyte Count (ARC) at Weeks 48 and 132

  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

  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

  Part A: Baseline (Day 1 of Part A) and Week 48; Part B: Baseline (Day 1 of Part B) and Week 132

Study Arms (2)

270mg or 360mg APL-2 administered subcutaneously daily (CAD)

EXPERIMENTAL

Drug: APL-2

270mg or 360mg APL-2 administered subcutaneously daily (wAIHA)

EXPERIMENTAL

Drug: APL-2

Interventions

APL-2 DRUG

Complement (C3) Inhibitor

270mg or 360mg APL-2 administered subcutaneously daily (CAD); 270mg or 360mg APL-2 administered subcutaneously daily (wAIHA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age.
• Weight \< 125 Kg.
• 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).
• Hemoglobin \<11 g/dL.
• Signs of hemolysis with abnormal values by any of the hemolytic markers:
• Increased absolute reticulocyte count (above ULN)
• Reduced haptoglobin (below LLN)
• Increased lactase dehydrogenase (LDH) (above ULN)
• Increased indirect bilirubin (above ULN)
• 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.
• 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.
• Able to provide documentary evidence of the following vaccinations within 2 years prior to screening:
• Neisseria meningitides types A, C, W, Y and type B (administered as two separate vaccinations)
• Streptococcus pneumoniae (Pneumococcal conjugate vaccine and Pneumococcal polysaccharide vaccine 23 \[PCV13 and/or PPSV23, respectively\])
• Haemophilus influenzae Type B (Hib) vaccine

You may not qualify if:

• Prior treatment with rituximab within 90 days.
• Deficiency of iron, folic acid and vitamin B12 prior to treatment phase
• Elevated bilirubin not due to active hemolysis. Any elevation of bilirubin \>ULN will require Sponsor review and approval for subject enrollment into the trial.
• 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.
• Presence or suspicion of active bacterial or viral infection, in the opinion of the Investigator, at screening or severe recurrent bacterial infections.
• Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days prior to screening period.
• Pregnant, breast-feeding, or intending to conceive during the course of the study, including the Post-Treatment Phase.
• 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.
• 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
• QTcF \> 470 ms
• PR \> 280 ms
• 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

Sponsors & Collaborators

• Apellis Pharmaceuticals, Inc.: lead

Study Sites (8)

American Institute of Research

Whittier, California, 90603, United States

Location

Lakes Research

Miami Lakes, Florida, 33014, United States

Location

Mid Florida Hematology Oncology

Orange City, Florida, 32763, United States

Location

University of Iowa Hospitals

Iowa City, Iowa, 52242, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

Related Publications (1)

• Roman E, Fattizzo B, Shum M, Hanna W, Lentz SR, Araujo SSS, Al-Adhami M, Grossi FV, Gertz MA. Safety and efficacy of pegcetacoplan treatment for cold agglutinin disease and warm antibody autoimmune hemolytic anemia. Blood. 2025 Jan 23;145(4):397-408. doi: 10.1182/blood.2023022549.

  PMID: 39486046 DERIVED

MeSH Terms

Conditions

Anemia, Hemolytic, Autoimmune

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Apellis Clinical Trial Information Line
• Organization: Apellis Pharmaceuticals, Inc

clinicaltrials@apellis.com

1-833-284-6361

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2017
• First Posted: July 24, 2017
• Study Start: August 31, 2017
• Primary Completion: September 12, 2022
• Study Completion: September 12, 2022
• Last Updated: December 12, 2024
• Results First Posted: December 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)