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CompletedNCT03427060CONSENTIIUpdated May 4, 2025Results posted

Coversin in PNH in Patients With Resistance to Eculizumab Due to Complement C5 Polymorphisms

A Phase 2 interventional study of Coversin in Paroxysmal Nocturnal Hemoglobinuria (PNH), sponsored by AKARI Therapeutics. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-05-04.

Sponsored by AKARI Therapeutics · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
1
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

Coversin in Paroxysmal Nocturnal Hemoglobinuria (PNH) in patients with resistance to Eculizumab due to complement C5 polymorphisms.

Read the 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.

02

Conditions studied

  • Paroxysmal Nocturnal Hemoglobinuria (PNH)
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts 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

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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
1 participant (actual)

Study arms

  • Experimental
    Coversin treatment

    Coversin - 22.5mg followed by 45mg for 6 months.

    Drug: Coversin

Interventions

  • DrugCoversin

    Coversin - 22.5mg followed by 45mg for 6 months.

05

What researchers measure

Primary outcomes

  1. Measurement of Serum Lactate Dehydrogenase (LDH)

    Measurement of serum lactate dehydrogenase (LDH)

    Time frame: Baseline to Day 186

Secondary outcomes

  1. 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

  2. Number of Packed Red Blood Cells (PRBC) Transfusions

    Number of units of packed red blood cells (PRBC) transfusions

    Time frame: Baseline to Day 180

06

Results

Posted May 4, 2025

Participant flow

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.

Participant flow — Overall Study
MilestoneCoversin Treatment
Started1
Completed1
Not completed0

Outcome measures

PrimaryMeasurement of Serum Lactate Dehydrogenase (LDH)

Measurement of serum lactate dehydrogenase (LDH)

Time frame:
Baseline to Day 186
Reported as:
Number · U/L
Measurement of Serum Lactate Dehydrogenase (LDH)
U/LCoversin Treatment
Screening2913
Day 13056
Day 31453
Day 7564
Day 14351
Day 21368
Day 29329
Day 36339
Day 43555
Day 60319
Day 90394
Day 120352
Day 150284
Day 183906
Day 184882
Day 186612
SecondaryPercentage 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
Reported as:
Number · %change in Hb value compare to screening
Percentage Change in Haemoglobin (Hb) Compared to Screening
%change in Hb value compare to screeningCoversin Treatment
Screening0
Day 128
Day 318
Day 722
Day 1417
Day 2125
Day 2923
Day 369
Day 4326
Day 6060
Day 9028
Day 12018
Day 15023
Day 18626
SecondaryNumber of Packed Red Blood Cells (PRBC) Transfusions

Number of units of packed red blood cells (PRBC) transfusions

Time frame:
Baseline to Day 180
Reported as:
Number · PRBC Units
Number of Packed Red Blood Cells (PRBC) Transfusions
PRBC UnitsCoversin Treatment
Day -351
Day -102
Day 381
Day 392

Adverse events

Collected over All adverse events were collected from the time of informed consent until completion of patient's study participation. From Screening to Day 186. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Coversin Treatment. Ablation Dose: Day 1. 60 mg and 30 mg (12 Hours Apart)0/1 (0%)0/1 (0%)0/1 (0%)
Coversin Treatment. Initiation Dose: Days 2 - 28. 22.5 mg Twice a Day (12 Hours Apart)0/1 (0%)1/1 (100%)1/1 (100%)
Coversin Treatment. Maintenance Dose: Days 29 - 180. 45 mg Once Daily0/1 (0%)0/1 (0%)0/1 (0%)
Most frequent serious events
Most frequent serious events
EventCoversin Treatment. Ablation Dose: Day 1. 60 mg and 30 mg (12 Hours Apart)Coversin Treatment. Initiation Dose: Days 2 - 28. 22.5 mg Twice a Day (12 Hours Apart)Coversin Treatment. Maintenance Dose: Days 29 - 180. 45 mg Once Daily
Device related InfectionInfections and infestations0/11/10/1
Febrile NeutropeniaBlood and lymphatic system disorders0/11/10/1
Urinary Tract InfectionInfections and infestations0/11/10/1
Most frequent other events
Most frequent other events
EventCoversin Treatment. Ablation Dose: Day 1. 60 mg and 30 mg (12 Hours Apart)Coversin Treatment. Initiation Dose: Days 2 - 28. 22.5 mg Twice a Day (12 Hours Apart)Coversin Treatment. Maintenance Dose: Days 29 - 180. 45 mg Once Daily
Aspartate Aminotransferase IncreasedInvestigations0/11/10/1
Hot FlushVascular disorders0/11/10/1
NauseaGastrointestinal disorders0/11/10/1
Urinary Tract InfectionInfections and infestations0/11/10/1
VomitingGastrointestinal disorders0/11/10/1
HypoglycaemiaMetabolism and nutrition disorders0/11/10/1
HeadacheNervous system disorders0/11/10/1

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Coversin Treatment
<=18 years0
Between 18 and 65 years1
>=65 years0
Sex: Female, Male
Sex: Female, Male(Participants)Coversin Treatment
Female1
Male0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Coversin Treatment
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White0
More than one race0
Unknown or Not Reported1
Height
Height(cm)Coversin Treatment
Number155
Weight
Weight(kg)Coversin Treatment
Number73.3
07

Study locations

1 site
  • Memorial Sloan Kettering Cancer Center
    New York, New York 10065, United States
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Feb 12, 2018

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03427060
Lead sponsor
AKARI Therapeutics
Responsible party
Sponsor
First posted
Feb 9, 2018
Start date
May 14, 2018
Primary completion
Nov 15, 2018
Completion
Feb 3, 2021
Results posted
May 4, 2025
Last update
May 4, 2025

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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