A Phase 2 interventional study of Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH), sponsored by AKARI Therapeutics. Completed at 1 site in Netherlands. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2023-07-12.
Sponsored by AKARI Therapeutics · Phase 2, Interventional, and Treatment
Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH) in patients with resistance to Eculizumab due to complement C5 polymorphisms.
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 for 2 years.
Please note, 'Coversin' is used throughout, but Nomacopan is the official name/INN.
Please note, the end points were assessed for 6 months, but the adverse events were measured over the 2 year period.
191 studies on the registry are indexed under Hemoglobinuria, Paroxysmal; 49 are open to participants now.
This study's enrollment of 1 is below the median of 33 across 150 interventional studies indexed under Hemoglobinuria, Paroxysmal.
Browse Hemoglobinuria, Paroxysmal studies →AKARI Therapeutics is the lead sponsor of 8 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
This is an open label, non-comparator study. Patient will be given a single ablating dose of 0.57mg/kg per subject followed by daily repeat maintenance doses. The initial repeat dose will be 25% of the ablating dose. If this is insufficient to maintain complement inhibition at ≤10% of baseline (pre-treatment) level after 5 days of treatment the daily dose will be increased by doubling until that level of inhibition is achieved. In the event of 100% inhibition being achieved the dose may be titrated downwards at the PI's discretion until a satisfactory clinical result is obtained. If at any point in treatment complement inhibition falls to less than 50% of baseline a further ablating dose of 0.57mg/kg should be given. Coversin lyophilised powder in each vial was diluted with 0.6 mL water for injection prior to use.
Drug: Coversin
Patients enrolled in this protocol will initially be treated with an ablating dose of Coversin and daily repeat maintenance doses calculated according to body weight, the ablating dose to be 0.57mg/kg. Thereafter the daily repeat dose will be titrated according to clinical response and complement inhibition determined by CH50 ELISA. The initial repeat dose will be 25% of the ablating dose and this will be adjusted up or down if necessary once steady state is reached (5 days).
Also known as: rVA576, rEV576
Measurement of Ratio of LDH to the Upper Limit of Normal (ULN)
LDH is an indicator of disease progression in patients with PNH and is expected to fall to within 2x upper limit of normal (ULN) within 28 days in successfully treated patients. Units are measured in ratio of LDH:ULN, where the ULN is 250 U/L. The primary efficacy endpoint was the LDH AUC from Day 0 to 28 compared with 28 days pretreatment. Data for the 28 days pre-treatment was not collected, and as only one patient was recruited, the LDH values compared with baseline and the ratio of LDH to the Upper Limit of Normal (ULN) are presented.
Time frame: Day 0 and Day 28
Number and Type of Adverse Events (AE)
The number and type of reported AEs will be recorded as well as the opinion of the Principle Investigator (PI) as to their possible relationship to the study drug.
Time frame: 2 years
Measurement of Haemoglobin (Hb) at Days 28, 90, and 180, Absolute and Change From Baseline
Measuring change in mean Hb from Day 28, Day 90 and Day 180 (absolute and change from baseline)
Time frame: Baseline, Day 28, Day 90 and Day 180
Measurement of Haptoglobin (Hp) at Days 28, 90 and 180, Absolute and Change From Baseline
Measuring change in mean Hp from Day 28, Day 90 and Day 180 (absolute and change from baseline)
Time frame: Baseline, Day 28, Day 90 and Day 180
Measurement of Lactate Dehydrogenase (LDH) at Baseline, Day 90 and Day 180
Measuring the change in LDH at Baseline, Day 90 and Day 180. LDH is an indicator of disease progression in patients with PNH and is expected to fall to within 2x upper limit of normal (ULN) within 28 days in successfully treated patients. Units are measured in ratio of LDH:ULN, where the ULN is 250 U/L.
Time frame: Baseline, Day 90 and Day 180
Change in Functional Assessment of Chronic Illness Therapy (FACIT) Score at Days 0, 28, 90 and 180
Functional Assessment of Chronic Illness Therapy - fatigue (FACIT-F) is a 13 item instrument designed to assess fatigue/tiredness and it's impact on daily activities and functioning in a chronic disease setting. The scale for each question in relation to quality of life ranges from 0-4 where 0= not at all, 1= a little bit, 2= somewhat, 3 = quite a bit and 4= very much. An increase in the scale score indicates an improvement in quality of life (less fatigue). A maximum score of 52 is interpreted as no fatigue . Baseline is assumed as 0.0 to demonstrate the change in units. The subscale score (as presented) is determined as per FACIT-f guidance, by multiplying the sum of the item scores by the number of items in the subscale, then divide by the number of items answered.
Time frame: Day 28, 90 and 180
Change in Quality Of Life Questionnaire (QOQ) Score at Days 0, 28, 90 and 180
The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 instrument measures the change in the quality of of life of patients in the trial. It comprises 30 questions on daily QOL and incorporates a global health status, five functional scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, nausea/vomiting, pain), and six single items (dyspnoea, insomnia, appetite loss, constipation, diarrhoea, financial difficulties). All of the scales range in score from 0 to 100, A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems. Scale scores were calculated by averaging items within scales and transforming average scores linearly.
Time frame: Day 28, 90 and 180
Dependency on Blood Transfusion
Number of participants depending on blood transfusion prior to starting the study compared to during the study.
Time frame: Day 0 through to study completion (2 years)
| Milestone | Coversin |
|---|---|
| Started | 1 |
| Completed | 1 |
| Not completed | 0 |
LDH is an indicator of disease progression in patients with PNH and is expected to fall to within 2x upper limit of normal (ULN) within 28 days in successfully treated patients. Units are measured in ratio of LDH:ULN, where the ULN is 250 U/L. The primary efficacy endpoint was the LDH AUC from Day 0 to 28 compared with 28 days pretreatment. Data for the 28 days pre-treatment was not collected, and as only one patient was recruited, the LDH values compared with baseline and the ratio of LDH to the Upper Limit of Normal (ULN) are presented.
| Ratio of LDH:ULN (250 U/L) | Coversin |
|---|---|
| Day 0 | 5.6 |
| Day 28 | 1.9 |
The number and type of reported AEs will be recorded as well as the opinion of the Principle Investigator (PI) as to their possible relationship to the study drug.
| Events | Coversin |
|---|---|
| Serious Adverse Events (SAE) | 2 |
| Adverse Event (AE) (total) | 20 |
| Treatment Emergent Adverse Event (TAEA) | 13 |
| AE - moderate | 1 |
| AE - severe | 1 |
| AE- mild | 18 |
Measuring change in mean Hb from Day 28, Day 90 and Day 180 (absolute and change from baseline)
| millimole(s)/litre | Coversin |
|---|---|
| Baseline | 8.2 |
| Day 28 (absolute) | 7.8 |
| Day 28 (change from baseline) | -0.7 |
| Day 90 (absolute) | 7.8 |
| Day 90 (change from baseline) | -0.4 |
| Day 180 (absolute) | 8.0 |
| Day 180 (change from baseline) | -0.2 |
Measuring change in mean Hp from Day 28, Day 90 and Day 180 (absolute and change from baseline)
| gram(s)/litre | Coversin |
|---|---|
| Baseline | NA |
| Day 28 | NA |
| Day 90 | NA |
| Day 180 | NA |
Measuring the change in LDH at Baseline, Day 90 and Day 180. LDH is an indicator of disease progression in patients with PNH and is expected to fall to within 2x upper limit of normal (ULN) within 28 days in successfully treated patients. Units are measured in ratio of LDH:ULN, where the ULN is 250 U/L.
| Ratio of LDH:ULN (250 U/L) | Coversin |
|---|---|
| Day 0 | 5.6 |
| Day 90 | 1.6 |
| Day 180 | 1.5 |
Functional Assessment of Chronic Illness Therapy - fatigue (FACIT-F) is a 13 item instrument designed to assess fatigue/tiredness and it's impact on daily activities and functioning in a chronic disease setting. The scale for each question in relation to quality of life ranges from 0-4 where 0= not at all, 1= a little bit, 2= somewhat, 3 = quite a bit and 4= very much. An increase in the scale score indicates an improvement in quality of life (less fatigue). A maximum score of 52 is interpreted as no fatigue . Baseline is assumed as 0.0 to demonstrate the change in units. The subscale score (as presented) is determined as per FACIT-f guidance, by multiplying the sum of the item scores by the number of items in the subscale, then divide by the number of items answered.
| FACIT-f scale (Change from Baseline) | Coversin |
|---|---|
| Day 28 | 13.0 |
| Day 90 | 13.3 |
| Day 180 | 11.0 |
The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 instrument measures the change in the quality of of life of patients in the trial. It comprises 30 questions on daily QOL and incorporates a global health status, five functional scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, nausea/vomiting, pain), and six single items (dyspnoea, insomnia, appetite loss, constipation, diarrhoea, financial difficulties). All of the scales range in score from 0 to 100, A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems. Scale scores were calculated by averaging items within scales and transforming average scores linearly.
| Scores on a scale (Change from baseline) | Coversin |
|---|---|
| Global Health Status/ QOL (day 28) | 16.7 |
| Global Health Status/ QOL (day 90) | 16.7 |
| Global Health Status/ QOL (day 180) | 16.7 |
| Physical Functioning (day 28) | 6.6 |
| Physical Functioning (day 90) | 0.0 |
| Physical Functioning (day 180) | 6.6 |
| Role functioning (day 28) | 33.4 |
| Role functioning (day 90) | 33.4 |
| Role functioning (day 180) | 16.7 |
| Emotional functioning (day 28) | 16.6 |
| Emotional functioning (day 90) | 8.3 |
| Emotional functioning (day 180) | 8.3 |
| Cognitive functioning (day 28) | 33.3 |
| Cognitive functioning (day 90) | 16.7 |
| Cognitive functioning (day 180) | 16.7 |
| Social functioning (day 28) | 0.0 |
| Social functioning (day 90) | 0.0 |
| Social functioning (day 180) | 0.0 |
| Fatigue symptom scale (day 28) | -11.1 |
| Fatigue symptom scale (day 90) | 0.0 |
| Fatigue symptom scale (day 180) | 0.0 |
| Nausea and vomiting symptom scale (day 28) | 0.0 |
| Nausea and vomiting symptom scale (day 90) | 0.0 |
| Nausea and vomiting symptom scale (day 180) | 0.0 |
| Pain symptom scale (day 28) | 0.0 |
| Pain symptom scale (day 90) | 16.7 |
| Pain symptom scale (day 180) | 0.0 |
| Symptom: Dyspnoea (day 28) | 0.0 |
| Symptom: Dyspnoea (day 90) | 0.0 |
| Symptom: Dyspnoea (day 180) | 0.0 |
| Symptom: Insomnia (day 28) | -33.3 |
| Symptom: Insomnia (day 90) | 0.0 |
| Symptom: Insomnia (day 180) | 0.0 |
| Symptom: Appetite loss (day 28) | 0.0 |
| Symptom: Appetite loss (day 90) | 0.0 |
| Symptom: Appetite loss (day 180) | 0.0 |
| Symptom: constipation (day 28) | 0.0 |
| Symptom: constipation (day 90) | 0.0 |
| Symptom: constipation (day 180) | 0.0 |
| Symptom: diarrhoea (day 28) | -33.3 |
| Symptom: diarrhoea (day 90) | -33.3 |
| Symptom: diarrhoea (day 180) | -33.3 |
| Symptom: financial difficulties (day 28) | 0.0 |
| Symptom: financial difficulties (day 90) | 0.0 |
| Symptom: financial difficulties (day 190) | 0.0 |
Number of participants depending on blood transfusion prior to starting the study compared to during the study.
| participants | Coversin |
|---|---|
| Transfusion dependent prior to starting trial | 0 |
| Transfusion dependent during trial | 0 |
Collected over Duration of the study (2 years). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Coversin | 0/1 (0%) | 1/1 (100%) | 1/1 (100%) |
| Event | Coversin |
|---|---|
| Breakthrough HemolysisBlood and lymphatic system disorders | 1/1 |
| Lung infectionInfections and infestations | 1/1 |
| Event | Coversin |
|---|---|
| Abdominal painGastrointestinal disorders | 1/1 |
| NauseaGastrointestinal disorders | 1/1 |
| CoughGeneral disorders | 1/1 |
| FatigueGeneral disorders | 1/1 |
| Flu like symptomsGeneral disorders | 1/1 |
| Injection site ReactionGeneral disorders | 1/1 |
| MalaiseGeneral disorders | 1/1 |
| Non-cardiac chest painGeneral disorders | 1/1 |
| Papulopustular rashInfections and infestations | 1/1 |
| HeadacheNervous system disorders | 1/1 |
| Age, Categorical(Participants) | Coversin |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 1 |
| >=65 years | 0 |
| Age, Continuous(years) | Coversin |
|---|---|
| Mean | 32 ± 0 |
| Sex: Female, Male(Participants) | Coversin |
|---|---|
| Female | 0 |
| Male | 1 |
| Race (NIH/OMB)(Participants) | Coversin |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 1 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Coversin |
|---|---|
| Netherlands | 1 |
| Weight(kg) | Coversin |
|---|---|
| Number | 67.8 |
| Height(cm) | Coversin |
|---|---|
| Number | 172 |
| Serum Lactate Dehydrogenase(U/L) | Coversin |
|---|---|
| Number | 1391 |
3 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
This study is completed, as verified in Feb 2017. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Nomacopan
AKARI Therapeutics