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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)

About this trial

This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria (PNH)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

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

NCT ID

NCT03588026

First Posted

June 1, 2018

Last Updated

November 3, 2020

Sponsor

AKARI Therapeutics

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

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

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

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

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

Learn more about this trial

Treating Paroxysmal Nocturnal Haemoglobinuria Patients With rVA576

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