Paroxysmal Nocturnal Hemoglobinuria (PNH)
Conditions
Brief summary
Coversin in Paroxysmal Nocturnal Hemoglobinuria (PNH) in patients with resistance to Eculizumab due to complement C5 polymorphisms.
Detailed description
Coversin, 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 and proven resistance to eculizumab due to C5 polymorphisms. Patients will be treated with Coversin by daily subcutaneous injection for 6 months 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 Coversin and being entered into the long term follow-up study.
Interventions
DRUGCoversin
Coversin - 22.5mg followed by 45mg for 6 months.
Sponsors
AKARI Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with known PNH. 2. Aged 18 and above. No upper age limit. 3. Lactate dehydrogenase (LDH) ≥1.5 upper limit of normal. 4. Must agree to use two methods of contraception that are ≥99% effective in preventing pregnancy. 5. Resistance to eculizumab (Soliris®). 6. Voluntary written informed consent. 7. Willing to self-inject Coversin daily. 8. Willing to receive appropriate prophylaxis against Neisseria infection. 9. Willing to avoid prohibited medications for duration of study.
Exclusion criteria
1. Subjects with body weight \<50 kg (110 lb) or \>100 kg (220 lb). 2. Pregnancy or breast feeding (females). 3. Known allergy to ticks or severe reaction to arthropod venom (e.g. bee or wasp venom). 4. Unresolved Neisseria meningitidis infection. 5. Patients who have not received adequate immunization against Neisseria meningitides. 6. Impaired hepatic function. 7. Patients with impaired renal function. 8. Failure to satisfy the Principal Investigator (PI) of fitness to participate for any other reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measurement of Serum Lactate Dehydrogenase (LDH) | Baseline to Day 186 | Measurement of serum lactate dehydrogenase (LDH) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Haemoglobin (Hb) Compared to Screening | Baseline to Day 186 | Percentage change in the haemoglobin (Hb) value at each study visit compared to screening |
| Number of Packed Red Blood Cells (PRBC) Transfusions | Baseline to Day 180 | Number of units of packed red blood cells (PRBC) transfusions |
Countries
United States
Participant flow
Recruitment details
Patients with paroxysmal nocturnal hemoglobinuria (PNH) who had received eculizumab without apparent benefit and in whom it had been demonstrated that their serum was resistant to eculizumab at any concentration (due to complement C5 polymorphisms that prevent tight binding of eculizumab) were recruited from one medical center between May 2018 and February 2021.
Pre-assignment details
There were no patients excluded from the study following enrolment
Participants by arm
| Arm | Count |
|---|---|
| Coversin Treatment This is an open label, non-comparator study.
Patients were to receive coversin at ablation, initiation and maintenance doses:
* Ablation (Day 1): 60 mg and 30 mg (12 hours apart)
* Initiation (Day 2 - 28): 22.5 mg twice a day
* Maintenance (Day 29 - 180): 45 mg once daily | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Coversin Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Height | 155 cm |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
| Weight | 73.3 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 0 / 1 | 1 / 1 | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 | 1 / 1 | 0 / 1 |
Outcome results
Primary
Measurement of Serum Lactate Dehydrogenase (LDH)
Measurement of serum lactate dehydrogenase (LDH)
Time frame: Baseline to Day 186
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Coversin Treatment | Measurement of Serum Lactate Dehydrogenase (LDH) | Screening | 2913 U/L |
| Coversin Treatment | Measurement of Serum Lactate Dehydrogenase (LDH) | Day 1 | 3056 U/L |
| Coversin Treatment | Measurement of Serum Lactate Dehydrogenase (LDH) | Day 3 | 1453 U/L |
| Coversin Treatment | Measurement of Serum Lactate Dehydrogenase (LDH) | Day 7 | 564 U/L |
| Coversin Treatment | Measurement of Serum Lactate Dehydrogenase (LDH) | Day 14 | 351 U/L |
| Coversin Treatment | Measurement of Serum Lactate Dehydrogenase (LDH) | Day 21 | 368 U/L |
| Coversin Treatment | Measurement of Serum Lactate Dehydrogenase (LDH) | Day 29 | 329 U/L |
| Coversin Treatment | Measurement of Serum Lactate Dehydrogenase (LDH) | Day 36 | 339 U/L |
| Coversin Treatment | Measurement of Serum Lactate Dehydrogenase (LDH) | Day 43 | 555 U/L |
| Coversin Treatment | Measurement of Serum Lactate Dehydrogenase (LDH) | Day 60 | 319 U/L |
| Coversin Treatment | Measurement of Serum Lactate Dehydrogenase (LDH) | Day 90 | 394 U/L |
| Coversin Treatment | Measurement of Serum Lactate Dehydrogenase (LDH) | Day 120 | 352 U/L |
| Coversin Treatment | Measurement of Serum Lactate Dehydrogenase (LDH) | Day 150 | 284 U/L |
| Coversin Treatment | Measurement of Serum Lactate Dehydrogenase (LDH) | Day 183 | 906 U/L |
| Coversin Treatment | Measurement of Serum Lactate Dehydrogenase (LDH) | Day 184 | 882 U/L |
| Coversin Treatment | Measurement of Serum Lactate Dehydrogenase (LDH) | Day 186 | 612 U/L |
Secondary
Number of Packed Red Blood Cells (PRBC) Transfusions
Number of units of packed red blood cells (PRBC) transfusions
Time frame: Baseline to Day 180
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Coversin Treatment | Number of Packed Red Blood Cells (PRBC) Transfusions | Day -35 | 1 PRBC Units |
| Coversin Treatment | Number of Packed Red Blood Cells (PRBC) Transfusions | Day -10 | 2 PRBC Units |
| Coversin Treatment | Number of Packed Red Blood Cells (PRBC) Transfusions | Day 38 | 1 PRBC Units |
| Coversin Treatment | Number of Packed Red Blood Cells (PRBC) Transfusions | Day 39 | 2 PRBC Units |
Secondary
Percentage Change in Haemoglobin (Hb) Compared to Screening
Percentage change in the haemoglobin (Hb) value at each study visit compared to screening
Time frame: Baseline to Day 186
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Coversin Treatment | Percentage Change in Haemoglobin (Hb) Compared to Screening | Screening | 0 %change in Hb value compare to screening |
| Coversin Treatment | Percentage Change in Haemoglobin (Hb) Compared to Screening | Day 1 | 28 %change in Hb value compare to screening |
| Coversin Treatment | Percentage Change in Haemoglobin (Hb) Compared to Screening | Day 3 | 18 %change in Hb value compare to screening |
| Coversin Treatment | Percentage Change in Haemoglobin (Hb) Compared to Screening | Day 7 | 22 %change in Hb value compare to screening |
| Coversin Treatment | Percentage Change in Haemoglobin (Hb) Compared to Screening | Day 14 | 17 %change in Hb value compare to screening |
| Coversin Treatment | Percentage Change in Haemoglobin (Hb) Compared to Screening | Day 21 | 25 %change in Hb value compare to screening |
| Coversin Treatment | Percentage Change in Haemoglobin (Hb) Compared to Screening | Day 29 | 23 %change in Hb value compare to screening |
| Coversin Treatment | Percentage Change in Haemoglobin (Hb) Compared to Screening | Day 36 | 9 %change in Hb value compare to screening |
| Coversin Treatment | Percentage Change in Haemoglobin (Hb) Compared to Screening | Day 43 | 26 %change in Hb value compare to screening |
| Coversin Treatment | Percentage Change in Haemoglobin (Hb) Compared to Screening | Day 60 | 60 %change in Hb value compare to screening |
| Coversin Treatment | Percentage Change in Haemoglobin (Hb) Compared to Screening | Day 90 | 28 %change in Hb value compare to screening |
| Coversin Treatment | Percentage Change in Haemoglobin (Hb) Compared to Screening | Day 120 | 18 %change in Hb value compare to screening |
| Coversin Treatment | Percentage Change in Haemoglobin (Hb) Compared to Screening | Day 150 | 23 %change in Hb value compare to screening |
| Coversin Treatment | Percentage Change in Haemoglobin (Hb) Compared to Screening | Day 186 | 26 %change in Hb value compare to screening |