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Study to Assess the Safety, Tolerability, Efficacy and PK of APL-2 in Patients With wAIHA or CAD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03226678
Recruitment Status : Active, not recruiting
First Posted : July 24, 2017
Last Update Posted : July 23, 2020
Sponsor:
Information provided by (Responsible Party):
Apellis Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE July 7, 2017
First Posted Date  ICMJE July 24, 2017
Last Update Posted Date July 23, 2020
Actual Study Start Date  ICMJE August 31, 2017
Actual Primary Completion Date November 26, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 9, 2019)
  • 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.
  • Change from baseline in hemoglobin [ Time Frame: Baseline to week 48 ]
    Efficacy endpoint assessment.
  • APL-2 serum concentrations and pharmacokinetic (PK) parameters [ Time Frame: Baseline to week 48 ]
    APL-2 serum concentrations and pharmacokinetic (PK) parameter (Cmax)
Original Primary Outcome Measures  ICMJE
 (submitted: July 19, 2017)
  • Total Number of AEs [ Time Frame: 12 months from baseline ]
    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.
  • Change from baseline in hemoglobin [ Time Frame: 6 months from baseline ]
    Efficacy endpoint assessment.
  • Cmax [ Time Frame: 12 months from baseline ]
    APL-2 serum concentrations and pharmacokinetic (PK) parameter (Cmax)
  • AUC [ Time Frame: 12 months from baseline ]
    APL-2 serum concentrations and pharmacokinetic (PK) parameter (AUC)
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Assess the Safety, Tolerability, Efficacy and PK of APL-2 in Patients With wAIHA or CAD
Official Title  ICMJE 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)
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Warm Autoimmune Hemolytic Anemia
  • Cold Agglutinin Disease
Intervention  ICMJE Drug: APL-2
Complement (C3) Inhibitor
Study Arms  ICMJE
  • Experimental: 270mg or 360mg APL-2 administered subcutaneously daily (CAD)
    Intervention: Drug: APL-2
  • Experimental: 270mg or 360mg APL-2 administered subcutaneously daily (wAIHA)
    Intervention: Drug: APL-2
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 5, 2018)
24
Original Estimated Enrollment  ICMJE
 (submitted: July 19, 2017)
12
Estimated Study Completion Date  ICMJE December 2020
Actual Primary Completion Date November 26, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03226678
Other Study ID Numbers  ICMJE APL2-CP-AIHA-208
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Apellis Pharmaceuticals, Inc.
Study Sponsor  ICMJE Apellis Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Apellis Pharmaceuticals, Inc.
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP