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

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ClinicalTrials.gov Identifier: NCT02588833
Recruitment Status : Recruiting
First Posted : October 28, 2015
Last Update Posted : April 10, 2018
Sponsor:
Information provided by (Responsible Party):
Apellis Pharmaceuticals, Inc.

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.


Condition or disease Intervention/treatment Phase
Paroxysmal Nocturnal Hemoglobinuria Drug: APL-2 Phase 1

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Study Start Date : November 2015
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2019


Arm Intervention/treatment
Experimental: Cohort 1
180 mg APL-2/day
Drug: APL-2
Experimental: Cohort 2
270 mg APL-2/day
Drug: APL-2
Experimental: Cohort 2 (Intra-subject)
Intra-subject escalation up to 360 mg APL-2/day
Drug: APL-2



Primary Outcome Measures :
  1. Number of treatment emergent adverse events (TEAEs) following administration of multiple doses of SC APL-2. [ Time Frame: changefrom baseline ]
  2. Severity of treatment emergent adverse events (TEAEs) following administration of multiple doses of SC APL-2. [ Time Frame: change from baseline ]


Information from the National Library of Medicine

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02588833


Locations
Hong Kong
Prince of Wales Hospital Recruiting
Hong Kong, Hong Kong
Contact: Raymond Wong    +852 73821966    raymondwong@cuhk.edu.hk   
Queen Mary Hospital Not yet recruiting
Hong Kong, Hong Kong
Contact: Eric TSE    852 2255 3975    ewctse@hku.hk   
Malaysia
Hospital Ampang Recruiting
Ampang, Selangor, Malaysia, 68000
Contact: Jameela SATHAR    60193889996    jsathar@hotmail.com   
New Zealand
Waikato Hospital Completed
Hamilton, Waikato, New Zealand, 3240
Thailand
Bangkok Hospital (Wattanosoth) Not yet recruiting
Bangkok, Thailand, 10310
Contact: Surapol ISSARAGRISIL    66819143828    surapolsi@gmail.com   
Rajavithi Hospital Not yet recruiting
Bangkok, Thailand, 10400
Contact: Kunapa IAM-ARUNTHAI    66873290921    kunapa@gmail.com   
Ramathibodi Hospital Recruiting
Bangkok, Thailand, 10400
Contact: Pimjai Niparuck    66868371441    niparuckblue@gmail.com   
Siriraj hospital Recruiting
Bangkok, Thailand, 10700
Contact: Surapol Issaragrisil    66819143828    surapolsi@gmail.com   
Phramongkutklao Hospital Recruiting
Bangkok, Thailand
Contact: Tontanai NUMBENJAPON    66802492227    tnumbenjapon@gmail.com   
Sponsors and Collaborators
Apellis Pharmaceuticals, Inc.
Investigators
Study Director: Federico Grossi, MD, PhD Apellis Pharmaceuticals, Inc.

Responsible Party: Apellis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02588833     History of Changes
Other Study ID Numbers: APL2-CP-PNH-204
First Posted: October 28, 2015    Key Record Dates
Last Update Posted: April 10, 2018
Last Verified: April 2018

Additional relevant MeSH terms:
Hemoglobinuria
Hemoglobinuria, Paroxysmal
Proteinuria
Urination Disorders
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Anemia, Hemolytic
Anemia
Hematologic Diseases
Myelodysplastic Syndromes
Bone Marrow Diseases