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Pilot Study to Assess Safety, Preliminary Efficacy and Pharmacokinetics of S.C. APL-2 in PNH Subjects (PADDOCK)

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: NCT02588833
Recruitment Status : Active, not recruiting
First Posted : October 28, 2015
Last Update Posted : January 22, 2019
Sponsor:
Information provided by (Responsible Party):
Apellis Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE October 27, 2015
First Posted Date  ICMJE October 28, 2015
Last Update Posted Date January 22, 2019
Study Start Date  ICMJE November 2015
Estimated Primary Completion Date September 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 28, 2018)
  • Number of treatment emergent adverse events (TEAEs) following administration of multiple doses of SC APL-2.Severity of treatment emergent adverse events (TEAEs) following administration of multiple doses of SC APL-2. [ Time Frame: change from baseline ]
  • LDH (U/L) [ Time Frame: change from baseline ]
  • Haptoglobin (mg/dL) & Hemoglobin (g/dl) [ Time Frame: change from baseline ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 27, 2015)
  • Number of treatment emergent adverse events (TEAEs) following administration of multiple doses of SC APL-2. [ Time Frame: 4 months from baseline ]
  • Severity of treatment emergent adverse events (TEAEs) following administration of multiple doses of SC APL-2. [ Time Frame: 4 months from baseline ]
Change History Complete list of historical versions of study NCT02588833 on ClinicalTrials.gov Archive Site
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 Pilot Study to Assess Safety, Preliminary Efficacy and Pharmacokinetics of S.C. APL-2 in PNH Subjects
Official Title  ICMJE A Phase Ib, Open Label, Multiple Ascending Dose, Pilot Study to Assess the Safety, Preliminary Efficacy and Pharmacokinetics of Subcutaneously Administered APL-2 in Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Brief Summary

The objectives of the study are to assess the safety, tolerability, preliminary efficacy and PK of multiple subcutaneous (SC) doses of APL-2 in subjects with paroxysmal nocturnal hemoglobinuria (PNH) who have not received treatment with eculizumab in the past.

An exploratory objective of the study is to assess the pharmacodynamics (PD) of multiple SC doses of APL 2 when administered to PNH patients.

Detailed Description

This is a Phase Ib, open-label, multiple ascending dose, pilot study in patients with PNH who have not received eculizumab (Soliris)® in the past. Two cohorts of 3 subjects are planned for evaluation.

Safety will be assessed throughout the study; serial blood and urine samples will be collected for these assessments. Blood samples will be collected for the assessment of APL 2 PK. Additional samples for assessment of PD will also be collected.

The study will consist of four parts;

  • Part 1: subjects will receive APL-2 for 28 days.
  • Part 2A: subjects may continue to receive APL-2 for a further 56 days if there is evidence of perceived clinical benefit following review of available safety, PK and PD data by the investigator and sponsor
  • Part 2B: subjects may continue to receive daily APL-2 treatment for up to 364 days if there is ongoing evidence of clinical benefit following review of the available safety, PK and PD data.
  • Part 3: Safety follow up Screening will take place within 30 days prior to the start of dosing on Day 1. If needed (see inclusion criteria), Neisseria menigitides types A, C, W, Y and B (administered as two separate vaccinations), Pneumococcal conjugate vaccine or Pneumococcal polysaccharide vaccine 23 (PCV13 or PPSV23, respectively), and Haemophilus influenzae Type B (Hib) vaccinations will be administered at least 14 days prior to dosing on Day 1.

Subjects will be entered into Part 1 of the study on Day 1 at a time designated by the PI. During Part 1, the first 3 daily SC doses of APL-2 (Day 1 to 3) as well as doses on Day 8, 15 and 22 will be administered at the clinical site. From Day 4 to Day 28 daily doses of APL-2 will be administered off-site by a trained study nurse at the subject's home, workplace, or other location convenient to the subject with the exception of those days where dosing is at the clinical site. Following ongoing review of available safety, PK and PD data by the investigator and sponsor, subjects showing evidence of perceived clinical benefit may progress to Part 2A and then to Part 2B of the study and continue to receive daily doses of APL 2 until Day 84 and then until Day 364.

Cohort 2 will not be initiated until all subjects in Cohort 1 have reached the Day 29 visit and the SMC has reviewed emerging safety and efficacy data and determined that, at the initial dose, APL-2 has an acceptable safety and tolerability profile.

The planned length of participation in the study for each subject in Cohort 2 is approximately 444 days (14.5 months) from Day 30 through completion of the Day 414 Exit visit procedures).

The study is planned to take place over approximately 24 months (from screening of Cohort 1 through completion of Cohort 2).

This time period may change in the event that the study is terminated early, additional cohorts are enrolled, additional time is required to review safety between cohorts, or extended safety and PK sampling is added for a cohort.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Paroxysmal Nocturnal Hemoglobinuria
Intervention  ICMJE Drug: APL-2
Complement (C3) Inhibitor
Study Arms  ICMJE
  • Experimental: Cohort 1
    180 mg APL-2/day
    Intervention: Drug: APL-2
  • Experimental: Cohort 2
    270 mg APL-2/day
    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: June 28, 2018)
20
Original Estimated Enrollment  ICMJE
 (submitted: October 27, 2015)
6
Estimated Study Completion Date  ICMJE September 2019
Estimated Primary Completion Date September 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female
  • At least 18 years old (inclusive)
  • Weigh >55 kg and have a body mass index (BMI) ≤38.0 kg/m2
  • Diagnosed with PNH (white blood cell (WBC) clone >10%)
  • Lactose dehydrogenase (LD) ≥2 times the upper limit of normal
  • Last transfusion within 12 months prior to screening
  • Platelet count of >30,000/mm3
  • Absolute neutrophil count >cells/500 µL
  • Women of child-bearing potential (WOCBP) must have a negative pregnancy test at screening and must agree to use protocol defined methods of contraception for the duration of the study
  • Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study
  • Able to provide documentary evidence of Neisseria meningitidis, Pneumococcal conjugate vaccine (multivalent) or Pneumococcal polysaccharide vaccine 23 (PCV13 or PPSV23) and Haemophilus influenzae Type B (Hib) vaccination within 2 years prior to Day 1 dosing, OR willing to receive vaccinations against Neisseria meningitidis at least two weeks prior to dosing on Day 1 with a booster on Day 57, and PCV13 and Hib vaccines at least two weeks prior to dosing on Day 1.
  • Willing and able to give informed consent

Exclusion Criteria:

  • Prior eculizumab (Soliris)® treatment
  • Active bacterial infection
  • Known infection with hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
  • Hereditary complement deficiency
  • History of bone marrow transplantation
  • Concurrent severe aplastic anemia (SAA), defined as currently receiving immunosuppressive therapy for SAA including but not limited to cyclosporin A, tacrolimus, mycophenolate mofetil or anti-thymocyte globulin.
  • Participation in any other investigational drug trial or exposure to another investigational agent, device or procedure within 30 days
  • Evidence of QTcF prolongation defined as >450 ms for males and >470 ms for females at screening
  • Creatinine clearance (CrCl) <50 mL/min (Cockcroft-Gault formula) at screening
  • Breast-feeding women
  • History of meningococcal disease
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 Hong Kong,   Malaysia,   New Zealand,   Thailand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02588833
Other Study ID Numbers  ICMJE APL2-CP-PNH-204
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 Not Provided
Responsible Party Apellis Pharmaceuticals, Inc.
Study Sponsor  ICMJE Apellis Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Federico Grossi, MD, PhD Apellis Pharmaceuticals, Inc.
PRS Account Apellis Pharmaceuticals, Inc.
Verification Date January 2019

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