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Warm Autoimmune Hemolytic AnemiaPhase 2NCT03226678

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)

A Phase 2 study testing APL-2 in people with Warm Autoimmune Hemolytic Anemia and Cold Agglutinin Disease, run by Apellis Pharmaceuticals, Inc. at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
APL-2
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
8 sitesUnited States
Study dates
31 Aug 2017to 12 Sep 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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
  • Subjects that do not have documentary evidence must be willing to receive any missing vaccinations as outlined below:
  • 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).
  • 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)
  • Haemophilus influenze Type B (Hib) must be administered prior to dosing on Day 1.
  • Willing and able to give informed consent.
  • 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).

Who cannot join

  • Prior treatment with rituximab within 90 days.
  • Deficiency of iron, folic acid and vitamin B12 prior to treatment phase
  • 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.
  • 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.
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  • 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

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • East Carolina University

    Greenville, North Carolina, 27834

  • University of Iowa Hospitals

    Iowa City, Iowa, 52242

  • University of Tennessee Medical Center

    Knoxville, Tennessee, 37920

  • Lakes Research

    Miami Lakes, Florida, 33014

  • Mid Florida Hematology Oncology

    Orange City, Florida, 32763

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Northwest Medical Specialties

    Tacoma, Washington, 98405

  • American Institute of Research

    Whittier, California, 90603

Other trials in United States

About this study

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)

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).

Being tested
APL-2
Medical subject headings
Anemia, Hemolytic, Autoimmune

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • APL-2Drug

    Complement (C3) Inhibitor

Study groups in NCT03226678
Study groupRoleWhat they receive
270mg or 360mg APL-2 administered subcutaneously daily (CAD)ExperimentalNot described
Receives: Drug: APL-2
270mg or 360mg APL-2 administered subcutaneously daily (wAIHA)ExperimentalNot described
Receives: Drug: APL-2

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. 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.

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

  2. Number of Subjects Who Received Red Blood Cell (RBC) Transfusions

    The number of on-study RBC transfusions were monitored throughout the treatment period.

    Measured: From Day 1 up to Week 132

  3. 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.

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

  4. 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.

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

  5. 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.

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

  6. 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.

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

  7. Maximum Observed Trough Serum Concentration (Ctrough,Max) of Pegcetacoplan

    Blood samples were collected for the assessment of Ctrough,max of pegcetacoplan.

    Measured: 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

  8. 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.

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

  9. 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jul 2017
  2. Study start31 Aug 2017
  3. Primary completion12 Sep 2022
  4. Study completion12 Sep 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03226678
Sponsor's protocol ID
APL2-CP-AIHA-208
Status last verified
Nov 2024
First submitted
7 Jul 2017
Last updated
12 Dec 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 39486046

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing APL-2 in people with Warm Autoimmune Hemolytic Anemia and Cold Agglutinin Disease, run by Apellis Pharmaceuticals, Inc. at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03226678, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2024.

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