Treating Paroxysmal Nocturnal Haemoglobinuria Patients With rVA576 (CAPSTONE)
Primary Purpose
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
rVA576
Standard of care (SOC)
Sponsored by
About this trial
This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria (PNH)
Eligibility Criteria
Inclusion Criteria:
- Willing to give informed consent to treatment with rVA576
- Diagnosed with paroxysmal nocturnal haemoglobinuria (PNH)
- Have not received any complement inhibitor within the 4 months prior to screening
- ≥ 18 years of age at the time of screening
- Weight ≥50kg
- Complete transfusion medical history for 12 months
- Transfusion dependent
- LDH ≥1.5 x the ULN
- Willing to receive appropriate prophylaxis against Neisseria meningitidis infection, by both immunisation and continuous or intermittent antibiotics
- Willing to avoid prohibited medications such as other complement inhibitors and chemotherapeutic agents
- 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.
- Patients who are on erythropoietin and/or immunosuppressant treatment should be on stable doses for at least 6 months.
- Patients who are taking systemic corticosteroids should be on a stable dose for at least 4 weeks.
- Patients on anticoagulant therapy should be well-controlled prior to entry.
- Patients taking iron and/or folic acid supplements should be on a stable dose for at least 4 weeks
Exclusion Criteria:
- Patients whose mean haemoglobin level over the previous 12 months prior to screening was greater than 105 g/L (10.5g/dL)
- Severe bone marrow failure
- Patients with a platelet count of ≤ 70 x 109/L
- Patients with known or suspected acquired somatic mutations affecting the bone marrow (e.g. acute myeloid leukaemia) which may be associated with PNH
- Chemotherapy within 3 months of screening visit
- History of recurrent bacterial infections or suspicion of active bacterial infections requiring antibiotic therapy
- Planned or actual pregnancy or breast feeding (females)
- Known allergy to ticks or severe reaction to arthropod venom (e.g. bee or wasp venom)
- Unresolved N. meningitidis infection.
- 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
- 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
- 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
- Participation in other clinical trials within 4 weeks of signing the consent form
- History of active systemic autoimmune diseases.
- Any other systemic disorders that could interfere with the evaluation of the study treatment
- Failure to comply with protocol requirements
- Known Hepatitis B or Hepatitis C
Sites / Locations
- Almaty City Hospital No.7
- Vilnius University Hospital Santaros Klinikos , Santariškių St. 2, LT-08661,
- University of Kelaniya, Faculty of Medicine, Thalagolla Road
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm 1 - 9 months of treatment (rVA576 plus SOC)
Arm 2 - 6 months on SOC
Arm Description
6 months (SOC plus rVA576), Followed by a further 3 months of (SOC plus rVA576).
6 months on SOC only. Followed by 3 months (SOC plus rVA576).
Outcomes
Primary Outcome Measures
HB (Haemoglobin) stabilisation rate and the avoidance of packed red blood cells (PRBC) transfusions
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.
Secondary Outcome Measures
Number of units of packed red blood cells (PRBC) transfused
Number of units of packed red blood cells (PRBC) transfused from Baseline Day 1 to Day 180
Percentage of patients who achieve transfusion avoidance
Percentage of patients who achieve transfusion avoidance
Change in (QOl) Quality of Life score
Change in Quality of Life score
AUC (LDH)
AUC (Area under the curve) (LDH) Lactate Dehydrogenase
CH50
CH50 (Classical haemolytic 50% lysis)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03588026
Brief Title
Treating Paroxysmal Nocturnal Haemoglobinuria Patients With rVA576
Acronym
CAPSTONE
Official Title
Investigational Product ; Coversin. Phase III Safety and Efficacy in Three-Part, Two-Arm, Randomised Open Label Evaluation in Patients With Paroxysmal Nocturnal Haemoglobinuria (PNH)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
June 7, 2018 (Actual)
Primary Completion Date
September 3, 2020 (Actual)
Study Completion Date
September 3, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AKARI Therapeutics
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paroxysmal Nocturnal Hemoglobinuria (PNH)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1 - 9 months of treatment (rVA576 plus SOC)
Arm Type
Experimental
Arm Description
6 months (SOC plus rVA576), Followed by a further 3 months of (SOC plus rVA576).
Arm Title
Arm 2 - 6 months on SOC
Arm Type
Experimental
Arm Description
6 months on SOC only. Followed by 3 months (SOC plus rVA576).
Intervention Type
Drug
Intervention Name(s)
rVA576
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Standard of care (SOC)
Intervention Description
6 months on SOC followed by 3 months of treatment with rVA576 plus SOC. In total, 3 months on rVA576 plus SOC.
Primary Outcome Measure Information:
Title
HB (Haemoglobin) stabilisation rate and the avoidance of packed red blood cells (PRBC) transfusions
Description
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.
Time Frame
9 months
Secondary Outcome Measure Information:
Title
Number of units of packed red blood cells (PRBC) transfused
Description
Number of units of packed red blood cells (PRBC) transfused from Baseline Day 1 to Day 180
Time Frame
Day 1 to Day 180
Title
Percentage of patients who achieve transfusion avoidance
Description
Percentage of patients who achieve transfusion avoidance
Time Frame
Day 1 to Day 180
Title
Change in (QOl) Quality of Life score
Description
Change in Quality of Life score
Time Frame
Day 1 to Day 180
Title
AUC (LDH)
Description
AUC (Area under the curve) (LDH) Lactate Dehydrogenase
Time Frame
Day 1 to Day 180
Title
CH50
Description
CH50 (Classical haemolytic 50% lysis)
Time Frame
Day 1 to Day 180
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Willing to give informed consent to treatment with rVA576
Diagnosed with paroxysmal nocturnal haemoglobinuria (PNH)
Have not received any complement inhibitor within the 4 months prior to screening
≥ 18 years of age at the time of screening
Weight ≥50kg
Complete transfusion medical history for 12 months
Transfusion dependent
LDH ≥1.5 x the ULN
Willing to receive appropriate prophylaxis against Neisseria meningitidis infection, by both immunisation and continuous or intermittent antibiotics
Willing to avoid prohibited medications such as other complement inhibitors and chemotherapeutic agents
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.
Patients who are on erythropoietin and/or immunosuppressant treatment should be on stable doses for at least 6 months.
Patients who are taking systemic corticosteroids should be on a stable dose for at least 4 weeks.
Patients on anticoagulant therapy should be well-controlled prior to entry.
Patients taking iron and/or folic acid supplements should be on a stable dose for at least 4 weeks
Exclusion Criteria:
Patients whose mean haemoglobin level over the previous 12 months prior to screening was greater than 105 g/L (10.5g/dL)
Severe bone marrow failure
Patients with a platelet count of ≤ 70 x 109/L
Patients with known or suspected acquired somatic mutations affecting the bone marrow (e.g. acute myeloid leukaemia) which may be associated with PNH
Chemotherapy within 3 months of screening visit
History of recurrent bacterial infections or suspicion of active bacterial infections requiring antibiotic therapy
Planned or actual pregnancy or breast feeding (females)
Known allergy to ticks or severe reaction to arthropod venom (e.g. bee or wasp venom)
Unresolved N. meningitidis infection.
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
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
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
Participation in other clinical trials within 4 weeks of signing the consent form
History of active systemic autoimmune diseases.
Any other systemic disorders that could interfere with the evaluation of the study treatment
Failure to comply with protocol requirements
Known Hepatitis B or Hepatitis C
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrius Degulys, MBBS
Organizational Affiliation
Vilnius University Hospital Santaros Klinikos
Official's Role
Principal Investigator
Facility Information:
Facility Name
Almaty City Hospital No.7
City
Almaty
State/Province
Microdistrict Kalkaman
ZIP/Postal Code
050006
Country
Kazakhstan
Facility Name
Vilnius University Hospital Santaros Klinikos , Santariškių St. 2, LT-08661,
City
Vilnius
ZIP/Postal Code
LT-08661
Country
Lithuania
Facility Name
University of Kelaniya, Faculty of Medicine, Thalagolla Road
City
Colombo
ZIP/Postal Code
Ragama/11010
Country
Sri Lanka
12. IPD Sharing Statement
Plan to Share IPD
No
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Treating Paroxysmal Nocturnal Haemoglobinuria Patients With rVA576
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