Treating Paroxysmal Nocturnal Haemoglobinuria Patients With rVA576

Paroxysmal Nocturnal Hemoglobinuria (PNH) Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03588026
• Other study ID #: AK580
• Status: Completed
• Phase: Phase 3
• Start date: June 7, 2018
• Est. completion date: September 3, 2020

Study information

• Verified date: November 2020
• Source: AKARI Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

rVA576 for patients with Paroxysmal Nocturnal Hemoglobinuria (PNH).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: September 3, 2020
• Est. primary completion date: September 3, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Paroxysmal Nocturnal Hemoglobinuria (PNH)

Intervention

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.

Locations

Country	Name	City	State
Kazakhstan	Almaty City Hospital No.7	Almaty	Microdistrict Kalkaman
Lithuania	Vilnius University Hospital Santaros Klinikos , Santariškiu St. 2, LT-08661,	Vilnius
Sri Lanka	University of Kelaniya, Faculty of Medicine, Thalagolla Road	Colombo

Sponsors (1)

Lead Sponsor	Collaborator
AKARI Therapeutics

Countries where clinical trial is conducted

Kazakhstan,  Lithuania,  Sri Lanka, 

Outcome

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