Trial Outcomes & Findings for Efficacy, Safety and Immunogenicity Study of Recombinant Human C1 Inhibitor for the Treatment of Acute HAE Attacks (NCT NCT01188564)

Last Updated: 2015-08-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

75 participants

Primary outcome timeframe

Patients observed for 24 hours

Results posted on

2015-08-07

Participant Flow

During the double blind phase of the study, patients were randomized once to receive rhC1INH or Saline in a ratio of 3:2. After the randomized treatment, patiënts with subsequent attacks could be trated with open-label rhC1INH.

Patients could be enrolled into the open-label phase of the study after the initial randomized treatment.

Participant milestones

Participant milestones
Measure	rhC1INH rhC1INH: 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) Placebo (Saline): One i.v. injection of saline (NaCl 0.9% w/v), equivalent in volume to the active treatment
Double-blind Phase STARTED	44	31
Double-blind Phase COMPLETED	43	31
Double-blind Phase NOT COMPLETED	1	0
Open Label Phase STARTED	24	20
Open Label Phase COMPLETED	24	20
Open Label Phase NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	rhC1INH rhC1INH: 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) Placebo (Saline): One i.v. injection of saline (NaCl 0.9% w/v), equivalent in volume to the active treatment
Double-blind Phase randomized not treated	1	0

Baseline Characteristics

Efficacy, Safety and Immunogenicity Study of Recombinant Human C1 Inhibitor for the Treatment of Acute HAE Attacks

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	rhC1INH n=44 Participants rhC1INH: 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) n=31 Participants Placebo (Saline): One i.v. injection of saline (NaCl 0.9% w/v), equivalent in volume to the active treatment	Total n=75 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=39 Participants	0 Participants n=41 Participants	1 Participants n=35 Participants
Age, Categorical Between 18 and 65 years	42 Participants n=39 Participants	29 Participants n=41 Participants	71 Participants n=35 Participants
Age, Categorical >=65 years	1 Participants n=39 Participants	2 Participants n=41 Participants	3 Participants n=35 Participants
Sex: Female, Male Female	28 Participants n=39 Participants	19 Participants n=41 Participants	47 Participants n=35 Participants
Sex: Female, Male Male	16 Participants n=39 Participants	12 Participants n=41 Participants	28 Participants n=35 Participants

PRIMARY outcome

Timeframe: Patients observed for 24 hours

Outcome measures

Outcome measures
Measure	rhC1INH n=43 Participants rhC1INH: 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) n=31 Participants Placebo (Saline): One i.v. injection of saline (NaCl 0.9% w/v), equivalent in volume to the active treatment
Time to Beginning of Relief of Symptoms	90 minutes Interval 61.0 to 150.0	152 minutes Interval 93.0 to The upper bound of the 95% confidence interval is not estimable due to censoring, and therefore an insufficient number of participants with events.

SECONDARY outcome

Timeframe: 24 hours

The key secondary efficacy endpoint was the time to minimal symptoms at all locations. The time to achieving minimal symptoms was defined as an answer of "Yes" to TEQ question 3.

Outcome measures

Outcome measures
Measure	rhC1INH n=44 Participants rhC1INH: 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) n=31 Participants Placebo (Saline): One i.v. injection of saline (NaCl 0.9% w/v), equivalent in volume to the active treatment
Time to Minimal Symptoms	303 minutes Interval 240.0 to 720.0	483 minutes Interval 300.0 to 1440.0

Adverse Events

rhC1INH

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo (Saline)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	rhC1INH n=56 participants at risk rhC1INH: 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) n=18 participants at risk Placebo (Saline): One i.v. injection of saline (NaCl 0.9% w/v), equivalent in volume to the active treatment
Gastrointestinal disorders Abdominal hernia	1.8% 1/56 • Number of events 1 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.	0.00% 0/18 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.

Other adverse events

Other adverse events
Measure	rhC1INH n=56 participants at risk rhC1INH: 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) n=18 participants at risk Placebo (Saline): One i.v. injection of saline (NaCl 0.9% w/v), equivalent in volume to the active treatment
Respiratory, thoracic and mediastinal disorders Sinus congestion	0.00% 0/56 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.	5.6% 1/18 • Number of events 1 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.
Respiratory, thoracic and mediastinal disorders Sneezing	1.8% 1/56 • Number of events 1 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.	0.00% 0/18 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.
Respiratory, thoracic and mediastinal disorders Vasomotor rhinitis	0.00% 0/56 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.	5.6% 1/18 • Number of events 1 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.
Gastrointestinal disorders Diarrhea	0.00% 0/56 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.	5.6% 1/18 • Number of events 1 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.
Gastrointestinal disorders Dyspepsia	0.00% 0/56 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.	5.6% 1/18 • Number of events 1 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.
Injury, poisoning and procedural complications Procedural headache	1.8% 1/56 • Number of events 1 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.	0.00% 0/18 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.
Investigations Fibrin D-dimer increased	1.8% 1/56 • Number of events 1 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.	0.00% 0/18 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.
Musculoskeletal and connective tissue disorders Back pain	1.8% 1/56 • Number of events 1 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.	0.00% 0/18 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	1.8% 1/56 • Number of events 1 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.	0.00% 0/18 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.
Skin and subcutaneous tissue disorders Skin burning sensation	1.8% 1/56 • Number of events 1 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.	0.00% 0/18 • From signing of the ICF till 90 days following each treated attack. If multiple attacks were treated, each was followed for 90 days. In the participants at risk rhC1INH arm group, patients that were randomized to Placebo in the Double Blind phase but received a rescue dose (rhC1INH) are included.

Additional Information

Anurag Relan, Vice President Clinical Research and Medical Affairs

Pharming Technologies

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee To ensure against inadvertent disclosure of confidential information, the PI will provide Sponsor an opportunity to review any proposed publication/disclosure before it is submitted or otherwise disclosed. The PI will submit proposed manuscript, publication or disclosure to the Sponsor for comment at least 60 days prior to its submission/disclosure. If requested, the publishing party shall remove any Information (other than Study results) prior to submitting or disclosing the materials.
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Restriction type: OTHER