Treating Paroxysmal Nocturnal Haemoglobinuria Patients With rVA576 (CAPSTONE)

Investigational Product ; Coversin. Phase III Safety and Efficacy in Three-Part, Two-Arm, Randomised Open Label Evaluation in Patients With Paroxysmal Nocturnal Haemoglobinuria (PNH)

rVA576 for patients with Paroxysmal Nocturnal Hemoglobinuria (PNH).

Study Overview

• Status: Completed
• Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
• Intervention / Treatment: Drug: rVA576; Other: Standard of care (SOC)

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: Interventional
• Enrollment (Actual): 9
• Phase: Phase 3

Contacts and Locations

Study Locations

• Kazakhstan
  • Microdistrict Kalkaman
    • Almaty, Microdistrict Kalkaman, Kazakhstan, 050006
      • Almaty City Hospital No.7
• Lithuania
  • Vilnius, Lithuania, LT-08661
    • Vilnius University Hospital Santaros Klinikos , Santariškių St. 2, LT-08661,
• Sri Lanka
  • Colombo, Sri Lanka, Ragama/11010
    • University of Kelaniya, Faculty of Medicine, Thalagolla Road

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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).	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.
Experimental: Arm 2 - 6 months on SOC; 6 months on SOC only. Followed by 3 months (SOC plus rVA576).	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Day 1 to Day 180
Percentage of patients who achieve transfusion avoidance	Percentage of patients who achieve transfusion avoidance	Day 1 to Day 180
Change in (QOl) Quality of Life score	Change in Quality of Life score	Day 1 to Day 180
AUC (LDH)	AUC (Area under the curve) (LDH) Lactate Dehydrogenase	Day 1 to Day 180
CH50	CH50 (Classical haemolytic 50% lysis)	Day 1 to Day 180

Collaborators and Investigators

• Sponsor: AKARI Therapeutics
• Investigators: Principal Investigator: Andrius Degulys, MBBS, Vilnius University Hospital Santaros Klinikos

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2018
• Primary Completion (Actual): September 3, 2020
• Study Completion (Actual): September 3, 2020

Study Registration Dates

• First Submitted: June 1, 2018
• First Submitted That Met QC Criteria: July 3, 2018
• First Posted (Actual): July 17, 2018

Study Record Updates

• Last Update Posted (Actual): November 4, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Urological Manifestations; Bone Marrow Diseases; Hematologic Diseases; Urination Disorders; Anemia; Proteinuria; Anemia, Hemolytic; Myelodysplastic Syndromes; Hemoglobinuria; Hemoglobinuria, Paroxysmal
• Other Study ID Numbers: AK580

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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