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Treating Paroxysmal Nocturnal Haemoglobinuria Patients With rVA576 (CAPSTONE)

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ClinicalTrials.gov Identifier: NCT03588026
Recruitment Status : Recruiting
First Posted : July 17, 2018
Last Update Posted : October 28, 2019
Sponsor:
Information provided by (Responsible Party):
AKARI Therapeutics

Tracking Information
First Submitted Date  ICMJE June 1, 2018
First Posted Date  ICMJE July 17, 2018
Last Update Posted Date October 28, 2019
Actual Study Start Date  ICMJE July 9, 2018
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 3, 2018)
HB (Haemoglobin) stabilisation rate and the avoidance of packed red blood cells (PRBC) transfusions [ Time Frame: 9 months ]
Haemoglobin stabilisation rate defined as haemoglobin greater than the set point for each patient during the pre-study randomisation period and the avoidance of PRBC transfusions during the treatment period.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 3, 2018)
  • Number of units of packed red blood cells (PRBC) transfused [ Time Frame: Day 1 to Day 180 ]
    Number of units of packed red blood cells (PRBC) transfused from Baseline Day 1 to Day 180
  • Percentage of patients who achieve transfusion avoidance [ Time Frame: Day 1 to Day 180 ]
    Percentage of patients who achieve transfusion avoidance
  • Change in (QOl) Quality of Life score [ Time Frame: Day 1 to Day 180 ]
    Change in Quality of Life score
  • AUC (LDH) [ Time Frame: Day 1 to Day 180 ]
    AUC (Area under the curve) (LDH) Lactate Dehydrogenase
  • CH50 [ Time Frame: Day 1 to Day 180 ]
    CH50 (Classical haemolytic 50% lysis)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treating Paroxysmal Nocturnal Haemoglobinuria Patients With rVA576
Official Title  ICMJE Investigational Product ; Coversin. Phase III Safety and Efficacy in Three-Part, Two-Arm, Randomised Open Label Evaluation in Patients With Paroxysmal Nocturnal Haemoglobinuria (PNH)
Brief Summary rVA576 for patients with Paroxysmal Nocturnal Hemoglobinuria (PNH).
Detailed Description

rVA576, a small protein complement C5 inhibitor which prevents the cleavage of C5 by C5 convertase into C5a and C5b, will be used in an open label, non-comparative clinical trial in patients with PNH.

Patients will be treated with rVA576 by daily subcutaneous injection in order to determine the safety and efficacy of the drug in these circumstances.

If satisfactory control of the PNH is achieved, and at the discretion of the Principal Investigator (PI), patients will have the option of remaining on rVA576 and being entered into the long term follow-up study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Paroxysmal Nocturnal Hemoglobinuria (PNH)
Intervention  ICMJE
  • Drug: rVA576
    6 months of treatment, rVA576 plus SOC. Followed by a further 3 months of rVA576 plus SOC. In total, 9 months on rVA576 plus SOC.
  • Other: Standard of care (SOC)
    6 months on SOC followed by 3 months of treatment with rVA576 plus SOC. In total, 3 months on rVA576 plus SOC.
Study Arms  ICMJE
  • Experimental: Arm 1 - 9 months of treatment (rVA576 plus SOC)
    6 months (SOC plus rVA576), Followed by a further 3 months of (SOC plus rVA576).
    Interventions:
    • Drug: rVA576
    • Other: Standard of care (SOC)
  • Experimental: Arm 2 - 6 months on SOC
    6 months on SOC only. Followed by 3 months (SOC plus rVA576).
    Interventions:
    • Drug: rVA576
    • Other: Standard of care (SOC)
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 3, 2018)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2020
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Willing to give informed consent to treatment with rVA576
  2. Diagnosed with paroxysmal nocturnal haemoglobinuria (PNH)
  3. Have not received any complement inhibitor within the 4 months prior to screening
  4. ≥ 18 years of age at the time of screening
  5. Weight ≥50kg
  6. Complete transfusion medical history for 12 months
  7. Transfusion dependent
  8. LDH ≥1.5 x the ULN
  9. Willing to receive appropriate prophylaxis against Neisseria meningitidis infection, by both immunisation and continuous or intermittent antibiotics
  10. Willing to avoid prohibited medications such as other complement inhibitors and chemotherapeutic agents
  11. Patients must agree to avoid pregnancy and fathering children from the time of signing the Informed Consent Form until 90 days after the last dose of rVA576.
  12. Patients who are on erythropoietin and/or immunosuppressant treatment should be on stable doses for at least 6 months.
  13. Patients who are taking systemic corticosteroids should be on a stable dose for at least 4 weeks.
  14. Patients on anticoagulant therapy should be well-controlled prior to entry.
  15. Patients taking iron and/or folic acid supplements should be on a stable dose for at least 4 weeks

Exclusion Criteria:

  1. Patients whose mean haemoglobin level over the previous 12 months prior to screening was greater than 105 g/L (10.5g/dL)
  2. Severe bone marrow failure
  3. Patients with a platelet count of ≤ 70 x 109/L
  4. Patients with known or suspected acquired somatic mutations affecting the bone marrow (e.g. acute myeloid leukaemia) which may be associated with PNH
  5. Chemotherapy within 3 months of screening visit
  6. History of recurrent bacterial infections or suspicion of active bacterial infections requiring antibiotic therapy
  7. Planned or actual pregnancy or breast feeding (females)
  8. Known allergy to ticks or severe reaction to arthropod venom (e.g. bee or wasp venom)
  9. Unresolved N. meningitidis infection.
  10. Patients who are not willing to receive adequate immunisation against N. meningitidis unless, in the opinion of the investigator, the risks of delaying therapy outweigh the risks of developing a meningococcal infection
  11. Impaired hepatic function unless, in the opinion of the investigator, the risks of delaying therapy outweigh the risks of treatment in the presence of impaired hepatic function
  12. Patients with a glomerular filtration rate (GFR) of <30mL/min/1.73m2 unless, in the opinion of the investigator, the risks of delaying therapy outweigh the risks of treatment in the presence of impaired renal function
  13. Participation in other clinical trials within 4 weeks of signing the consent form
  14. History of active systemic autoimmune diseases.
  15. Any other systemic disorders that could interfere with the evaluation of the study treatment
  16. Failure to comply with protocol requirements
  17. Known Hepatitis B or Hepatitis C
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: Wynne Weston-Davies 020 8004 0967 ext 0268 wynne.weston-davies@akaritx.com
Contact: Miles Nunn 020 8004 0267 ext 0267 miles.nunn@akaritx.com
Listed Location Countries  ICMJE Kazakhstan,   Lithuania,   Sri Lanka
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03588026
Other Study ID Numbers  ICMJE AK580
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party AKARI Therapeutics
Study Sponsor  ICMJE AKARI Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Andrius Degulys, MBBS Vilnius University Hospital Santaros Klinikos
PRS Account AKARI Therapeutics
Verification Date February 2019

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