Paroxysmal Nocturnal Haemoglobinuria (PNH) Clinical Trial
Official title:
Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH) in Patients With Resistance to Eculizumab Due to Complement C5 Polymorphisms
| NCT number | NCT02591862 |
| Other study ID # | AK578 |
| Secondary ID | |
| Status | Completed |
| Phase | Phase 2 |
| First received | |
| Last updated | |
| Start date | February 2016 |
| Est. completion date | March 20, 2018 |
| Verified date | February 2017 |
| Source | AKARI Therapeutics |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH) in patients with resistance to Eculizumab due to complement C5 polymorphisms.
| Status | Completed |
| Enrollment | 1 |
| Est. completion date | March 20, 2018 |
| Est. primary completion date | March 20, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 80 Years |
| Eligibility | Inclusion Criteria: - Patients with known Paroxysmal Nocturnal Haemoglobinuria (PNH) - LDH >=1.5 Upper Limit of Normal (ULN) - Resistance to Eculizumab proven by both a recognised C5 polymorphism on genetic screening and complement inhibition on CH50 ELISA of <100% at concentrations of Eculizumab in excess of 50 µg/mL - Willing to self-inject Coversin daily or to receive daily subcutaneous injections by a home nurse or in a doctor's office or hospital clinic - Males or females taking adequate contraceptive precautions if of childbearing potential, 18 - 80 years of age - Body weight =50kg and = 100kg - The patient has provided written informed consent. - Willing to avoid prohibited medications for duration of study - Must agree to take appropriate prophylactic precautions against Neisseria infection. - Must be counselled regarding the possible reproductive risks of using Coversin and be advised to use an adequate method of contraception pending further data on reproductive toxicology. Exclusion Criteria: - Body weight <50kg or>100kg - Pregnancy (females) - Failure to satisfy the PI of fitness to participate for any other reason - Known allergy to ticks or severe reaction to arthropod venom (e.g., bee or wasp venom) |
| Country | Name | City | State |
|---|---|---|---|
| Netherlands | Dr Saskia Langemeijer | Nijmegen |
| Lead Sponsor | Collaborator |
|---|---|
| AKARI Therapeutics | Radboud University Medical Center |
Netherlands,
Schols S, Nunn MA, Mackie I, Weston-Davies W, Nishimura JI, Kanakura Y, Blijlevens N, Muus P, Langemeijer S. Successful treatment of a PNH patient non-responsive to eculizumab with the novel complement C5 inhibitor coversin (nomacopan). Br J Haematol. 202 — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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. | Day 0 and Day 28 | |
| Primary | 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. | 2 years | |
| Secondary | 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) | Baseline, Day 28, Day 90 and Day 180 | |
| Secondary | 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) | Baseline, Day 28, Day 90 and Day 180 | |
| Secondary | 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. | Baseline, Day 90 and Day 180 | |
| Secondary | 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. |
Day 28, 90 and 180 | |
| Secondary | 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. | Day 28, 90 and 180 | |
| Secondary | Dependency on Blood Transfusion | Number of participants depending on blood transfusion prior to starting the study compared to during the study. | Day 0 through to study completion (2 years) |