Treating Paroxysmal Nocturnal Haemoglobinuria Patients With rVA576

NCT ID: NCT03588026

Last Updated: 2025-04-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-07
• Study Completion Date: 2020-09-03

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.

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1 - 9 months of treatment (rVA576 plus SOC)

6 months (SOC plus rVA576), Followed by a further 3 months of (SOC plus rVA576).

Group Type: EXPERIMENTAL

rVA576

Intervention Type: DRUG

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.

Standard of care (SOC)

Intervention Type: OTHER

6 months on SOC followed by 3 months of treatment with rVA576 plus SOC. In total, 3 months on rVA576 plus SOC.

Arm 2 - 6 months on SOC

6 months on SOC only. Followed by 3 months (SOC plus rVA576).

Group Type: EXPERIMENTAL

rVA576

Intervention Type: DRUG

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.

Standard of care (SOC)

Intervention Type: OTHER

6 months on SOC followed by 3 months of treatment with rVA576 plus SOC. In total, 3 months on rVA576 plus SOC.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AKARI Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrius Degulys, MBBS

Role: PRINCIPAL_INVESTIGATOR

Vilnius University Hospital Santaros Klinikos

Locations

Almaty City Hospital No.7

Almaty, Microdistrict Kalkaman, Kazakhstan

Vilnius University Hospital Santaros Klinikos , Santariškių St. 2, LT-08661,

Vilnius, , Lithuania

University of Kelaniya, Faculty of Medicine, Thalagolla Road

Colombo, , Sri Lanka

Countries

Kazakhstan; Lithuania; Sri Lanka

Other Identifiers

AK580

Identifier Type: -

Identifier Source: org_study_id