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Also known as rhC1INH, Ruconest, Conestat alfa
Recombinant human C1 inhibitor · 7 trials · 4 indications
Time to beginning of relief is the time lapsed from the beginning of the infusion of study medication to the beginning of a beneficial effect based on patient's responses to the Treatmetn Effect Questionnaire (TEQ) for the primary attack location. The beginning of relief is defined as the first timepoint at which * The patient reports any of the following answers for TEQ question 1: "A little better", "Better" or "Much better"; and; * The patient reports the following answer for TEQ question 2: "Yes"; and, * There is persistence in improvement at the next assessment time, i.e.either the same or a better response to Question 1 and "Yes" to Question 2.
The disease severity on the 7-point WHO Ordinal Scale on Day 7 was the primary objective of this study. This endpoint had been suggested by the WHO for clinical trials in patients with Covid-19. The ordinal scale measures illness severity over time. The higher score, the worst outcome: meaning score 1, no limitation in activities and score 7, death.
Average number of HAE attacks normalized to a 28 day period
Time to beginning of relief of symptoms that showed the response to treatment based on the overall VAS score decrease of ≥ 20 mm from baseline. Separate VAS forms will be given to express the current feelings considering the severity of angioedema symptoms for five possible anatomical locations. The form will be completed by placing vertical marks on each of the 100 mm horizontal lines. The Abdominal VAS measures the patient's perceptions relating to illness, pain, bloodedness, and nausea; the oro-pharyngeal-laryngeal (OPL) VAS measures illness, pain, swelling, breathing, speech, and swallowing; the facial VAS instrument measure illness, pain and swelling; the Peripheral VAS measures swelling, pain, and use of extremity; and the Urogenital VAS measures illness, pain, swelling, nausea, and urination. Time to beginning of relief will also be calculated based on the Investigator Score (IS) and Treatment Effect Questionnaire (TEQ).
Prior to the treatment period, patients enrolled in the study, were asked about the amount of "HAE" attacks in the past 2 years, (calculated to attacks/week), this number is defined as "Historical". During the treatment period, patients received a dose of 50 IU/kg of "rhC1INH" administered by slow "IV" injection over 4 to 5 minutes, once a week during an eight week period. The amount of attacks during this period is defined as "Prophylaxis" (calculated to attacks/week).
| Arm | Type | Description |
|---|---|---|
| rhC1INH | EXPERIMENTAL | - |
| Placebo (Saline) | PLACEBO_COMPARATOR | - |
| 100 IU/kg "rhC1INH" | EXPERIMENTAL | 100 IU/kg recombinant human C1 inhibitor |
| Saline | PLACEBO_COMPARATOR | Saline solution |
| Ruconest | EXPERIMENTAL | Patients receive (150 U/ml) of Ruconest at a 50 U/kg dose (max dose of 4200 U) as a slow intravenous injection via a peripheral every 12 hours; for 4 days. A total of 8 doses will be administered. |
| Standard of Care | OTHER | SOC |
| rhC1INH twice weekly | EXPERIMENTAL | rhC1INH administered twice weekly |
| rhC1INH once weekly | EXPERIMENTAL | rhC1INH administered once weekly |
| Placebo (Saline) twice weekly | PLACEBO_COMPARATOR | Placebo (Saline) administered twice weekly |
| Recombinant Human C1 Inhibitor | EXPERIMENTAL | Patients presented to the clinic within 5 hours of onset received rhC1INH 50 U/kg body weight up to a maximum of 4200 U. |
| 100 IU/kg rhC1INH | EXPERIMENTAL | 100 IU/kg Recombinant human C1 inhibitor |
| 50 IU/kg rhC1INH | EXPERIMENTAL | 50 IU/kg Recombinant human C1 inhibitor |
| Name | Type | Description |
|---|---|---|
| rhC1INH | DRUG | One i.v. injection of rhC1INH at the dose of 50 U/kg, for patients up to 84 kg; one i.v. injection of rhC1INH at the dose of 4200U (2 vials) for patients of 84 kg body weight or greater. |
| Placebo (Saline) | DRUG | One i.v. injection of saline (NaCl 0.9% w/v), equivalent in volume to the active treatment |
| recombinant human C1 inhibitor | DRUG | IV |
| Placebo | DRUG | IV |
| Ruconest | DRUG | Patients will be randomized to Ruconest or Standard of Care |
Inclusion Criteria: * Aged at least 13 years * Signed written informed consent * Clear clinical and laboratory diagnosis of HAE with baseline plasma level of functional C1INH of less than 50% of normal * Willingness and ability to comply with all protocol procedures * Clinical symptoms of an eligib...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Intellia Therapeutics, Inc. | NTLA | 3 | PHASE3 | NTLA-2002 |
| BioCryst Pharmaceuticals, Inc. | BCRX | 2 | PHASE3 | Berotralstat |
| Ionis Pharmaceuticals, Inc. | IONS | 1 | PHASE3 | Donidalorsen |
| Pharvaris N.V. | PHVS | 1 | PHASE2 | Deucrictibant |
| BioMarin Pharmaceutical Inc. | BMRN | 1 | PHASE1 | BMN 331 |
| Astria Therapeutics, Inc. | ATXS | 1 | PHASE2 | STAR-0215 |
Recombinant human C1 inhibitor is used for hereditary angioedema, a genetic disorder marked by recurrent swelling attacks. It has been studied both for treating acute attacks and for prophylaxis, meaning routine use to prevent attacks. It is being developed by Pharming Group N.V. for these rare disease indications.
Recombinant human C1 inhibitor is an exogenous protein. It is associated with the F9 target, and its target class is an exogenous protein. It is a small molecule modality in development for hereditary angioedema and related genetic disorders.
Pharming Group N.V., which trades under the ticker PHAR, is the developer of recombinant human C1 inhibitor. The company is advancing the asset for hereditary angioedema and related genetic disorders within the rare disease therapeutic area.
Recombinant human C1 inhibitor is in Phase 2 development. It is investigational and is not approved. Three completed trials are recorded, with no active trials at present. The program includes one Phase 3 study and several Phase 2 studies, all of which have been completed.
Completed trials include NCT02247739, a Phase 2 hereditary angioedema prophylaxis study with 32 participants across the United States, Canada, Czechia, Italy, North Macedonia, Romania and Serbia. Other completed studies are NCT00851409, NCT00262301 and NCT00225147. Total enrollment across the program is 184 participants.
Recombinant human C1 inhibitor is a distinct recombinant product developed by Pharming Group N.V. under the ticker PHAR. It is studied for hereditary angioedema and related genetic disorders, and it is identified by the ChEMBL ID CHEMBL2109205.