Trial Outcomes & Findings for Efficacy and Safety Study of DX-2930 to Prevent Acute Angioedema Attacks in Patients With Type I and Type II HAE (NCT NCT02586805)

Last Updated: 2021-06-02

Results Overview

HAE attack was defined as a discrete episode during which the participant progressed from no angioedema to symptoms of angioedema. Rate of investigator confirmed HAE attacks was analyzed using a generalized linear model (GLM) for count data assuming a poisson distribution with a log link function and Pearson chi-square scaling of standard errors to account for potential overdispersion. The logarithm of time in days each subject was observed during the treatment period was used as an offset variable in the model.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

125 participants

Primary outcome timeframe

From Day 0 to Day 182

Results posted on

2021-06-02

Participant Flow

The study was conducted at 41 sites in the United States, United Kingdom, Italy, Germany, Canada and Jordan between 03 March 2016 (first participant first visit) and 13 April 2017 (last participant last visit).

A total of 159 participants were screened and 126 participants were randomized in the ratio of 3:2:2:2 to the placebo versus DX-2930-03 arms. Of them, 125 participants were assigned to study treatment and one participant determined to be screen failure after randomization.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo matched to DX-2930 subcutaneously (SC) once in every 2 weeks (q2wks) for 26 weeks.	Lanadelumab (DX-2930) 150 mg Every 4 Weeks Participants received 150 milligram (mg) dose of DX-2930 SC once in every 4 weeks (q4wks) and matched placebo SC q2wks between DX-2930 doses for 26 weeks.	Lanadelumab (DX-2930) 300 mg Every 4 Weeks Participants received 300 mg dose of DX-2930 SC q4wks and matched placebo SC q2wks between DX-2930 doses for 26 weeks.	Lanadelumab (DX-2930) 300 mg Every 2 Weeks Participants received 300 mg dose of DX-2930 SC q2wks for 26 weeks.
Overall Study STARTED	41	28	29	27
Overall Study COMPLETED	35	27	26	25
Overall Study NOT COMPLETED	6	1	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo matched to DX-2930 subcutaneously (SC) once in every 2 weeks (q2wks) for 26 weeks.	Lanadelumab (DX-2930) 150 mg Every 4 Weeks Participants received 150 milligram (mg) dose of DX-2930 SC once in every 4 weeks (q4wks) and matched placebo SC q2wks between DX-2930 doses for 26 weeks.	Lanadelumab (DX-2930) 300 mg Every 4 Weeks Participants received 300 mg dose of DX-2930 SC q4wks and matched placebo SC q2wks between DX-2930 doses for 26 weeks.	Lanadelumab (DX-2930) 300 mg Every 2 Weeks Participants received 300 mg dose of DX-2930 SC q2wks for 26 weeks.
Overall Study Withdrawal by Subject	3	1	1	2
Overall Study Adverse Event	2	0	1	0
Overall Study Lost to Follow-up	0	0	1	0
Overall Study Physician Decision	1	0	0	0

Baseline Characteristics

Efficacy and Safety Study of DX-2930 to Prevent Acute Angioedema Attacks in Patients With Type I and Type II HAE

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=41 Participants Participants received placebo matched to DX-2930 SC q2wks for 26 weeks.	Lanadelumab (DX-2930) 150 mg Every 4 Weeks n=28 Participants Participants received 150 mg dose of DX-2930 SC q4wks and matched placebo SC q2wks between DX-2930 doses for 26 weeks.	Lanadelumab (DX-2930) 300 mg Every 4 Weeks n=29 Participants Participants received 300 mg dose of DX-2930 SC q4wks and matched placebo SC q2wks between DX-2930 doses for 26 weeks.	Lanadelumab (DX-2930) 300 mg Every 2 Weeks n=27 Participants Participants received 300 mg dose of DX-2930 SC q2wks for 26 weeks.	Total n=125 Participants Total of all reporting groups
Age, Continuous	40.1 Years STANDARD_DEVIATION 16.75 • n=93 Participants	43.4 Years STANDARD_DEVIATION 14.91 • n=4 Participants	39.5 Years STANDARD_DEVIATION 12.85 • n=27 Participants	40.3 Years STANDARD_DEVIATION 13.35 • n=483 Participants	40.7 Years STANDARD_DEVIATION 14.69 • n=36 Participants
Sex: Female, Male Female	34 Participants n=93 Participants	20 Participants n=4 Participants	19 Participants n=27 Participants	15 Participants n=483 Participants	88 Participants n=36 Participants
Sex: Female, Male Male	7 Participants n=93 Participants	8 Participants n=4 Participants	10 Participants n=27 Participants	12 Participants n=483 Participants	37 Participants n=36 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants	3 Participants n=483 Participants	9 Participants n=36 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	38 Participants n=93 Participants	27 Participants n=4 Participants	27 Participants n=27 Participants	23 Participants n=483 Participants	115 Participants n=36 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants

PRIMARY outcome

Timeframe: From Day 0 to Day 182

Population: ITT population included all randomized participants who received any exposure to the investigational product.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received placebo matched to DX-2930 SC q2wks for 26 weeks.	Lanadelumab (DX-2930) 150 mg Every 4 Weeks n=28 Participants Participants received 150 mg dose of DX-2930 SC q4wks and matched placebo SC q2wks between DX-2930 doses for 26 weeks.	Lanadelumab (DX-2930) 300 mg Every 4 Weeks n=29 Participants Participants received 300 mg dose of DX-2930 SC q4wks and matched placebo SC q2wks between DX-2930 doses for 26 weeks.	Lanadelumab (DX-2930) 300 mg Every 2 Weeks n=27 Participants Participants received 300 mg dose of DX-2930 SC q2wks for 26 weeks.
Rate of Investigator Confirmed Hereditary Angioedema (HAE) Attacks During Treatment Period	1.967 Attacks per 4 weeks Interval 1.64 to 2.358	0.480 Attacks per 4 weeks Interval 0.313 to 0.735	0.526 Attacks per 4 weeks Interval 0.358 to 0.771	0.257 Attacks per 4 weeks Interval 0.145 to 0.458

SECONDARY outcome

Timeframe: From Day 0 to Day 182

Population: ITT population included all randomized participants who received any exposure to the investigational product.

HAE attack was defined as a discrete episode during which the participant progressed from no angioedema to symptoms of angioedema. Rate of investigator confirmed HAE attack was analyzed using the GLM for count data assuming a poisson distribution with a log link function and Pearson chi-square scaling of standard errors to account for potential overdispersion. The logarithm of time in days each subject was observed during the treatment period was used as an offset variable in the model.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received placebo matched to DX-2930 SC q2wks for 26 weeks.	Lanadelumab (DX-2930) 150 mg Every 4 Weeks n=28 Participants Participants received 150 mg dose of DX-2930 SC q4wks and matched placebo SC q2wks between DX-2930 doses for 26 weeks.	Lanadelumab (DX-2930) 300 mg Every 4 Weeks n=29 Participants Participants received 300 mg dose of DX-2930 SC q4wks and matched placebo SC q2wks between DX-2930 doses for 26 weeks.	Lanadelumab (DX-2930) 300 mg Every 2 Weeks n=27 Participants Participants received 300 mg dose of DX-2930 SC q2wks for 26 weeks.
Rate of Investigator Confirmed Hereditary Angioedema (HAE) Attack Requiring Acute Treatment	1.637 Attacks per 4 weeks Interval 1.337 to 2.005	0.314 Attacks per 4 weeks Interval 0.184 to 0.535	0.423 Attacks per 4 weeks Interval 0.276 to 0.648	0.208 Attacks per 4 weeks Interval 0.109 to 0.396

SECONDARY outcome

Timeframe: From Day 0 to Day 182

Population: ITT population included all randomized participants who received any exposure to the investigational product.

HAE attack was defined as a discrete episode during which the participant progressed from no angioedema to symptoms of angioedema. Moderate and severe investigator-confirmed HAE attacks were the attacks that were moderate or severe as per the HAE attack assessment and reporting procedures (HAARP) defined severity. The overall severity of attack was determined by the investigator using following definitions: mild (transient or mild discomfort), moderate (mild to moderate limitation in activity), severe (marked limitation in activity). Rate of moderate or severe investigator confirmed HAE attack was analyzed using the GLM for count data assuming a poisson distribution with a log link function and Pearson chi-square scaling of standard errors to account for potential overdispersion. The logarithm of time in days each subject was observed during the treatment period was used as an offset variable in the model.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received placebo matched to DX-2930 SC q2wks for 26 weeks.	Lanadelumab (DX-2930) 150 mg Every 4 Weeks n=28 Participants Participants received 150 mg dose of DX-2930 SC q4wks and matched placebo SC q2wks between DX-2930 doses for 26 weeks.	Lanadelumab (DX-2930) 300 mg Every 4 Weeks n=29 Participants Participants received 300 mg dose of DX-2930 SC q4wks and matched placebo SC q2wks between DX-2930 doses for 26 weeks.	Lanadelumab (DX-2930) 300 mg Every 2 Weeks n=27 Participants Participants received 300 mg dose of DX-2930 SC q2wks for 26 weeks.
Rate of Moderate or Severe Investigator Confirmed Hereditary Angioedema (HAE) Attacks	1.216 Attacks per 4 weeks Interval 0.971 to 1.522	0.359 Attacks per 4 weeks Interval 0.221 to 0.581	0.325 Attacks per 4 weeks Interval 0.199 to 0.529	0.202 Attacks per 4 weeks Interval 0.106 to 0.386

SECONDARY outcome

Timeframe: From Day 14 to Day 182

Population: ITT population included all randomized participants who received any exposure to the investigational product.

HAE attack was defined as a discrete episode during which the participant progressed from no angioedema to symptoms of angioedema. Rate of investigator confirmed HAE attacks during day 14 after study drug administration through day 182 was analyzed by the same poisson regression model as in the primary endpoint analysis.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Participants received placebo matched to DX-2930 SC q2wks for 26 weeks.	Lanadelumab (DX-2930) 150 mg Every 4 Weeks n=28 Participants Participants received 150 mg dose of DX-2930 SC q4wks and matched placebo SC q2wks between DX-2930 doses for 26 weeks.	Lanadelumab (DX-2930) 300 mg Every 4 Weeks n=29 Participants Participants received 300 mg dose of DX-2930 SC q4wks and matched placebo SC q2wks between DX-2930 doses for 26 weeks.	Lanadelumab (DX-2930) 300 mg Every 2 Weeks n=27 Participants Participants received 300 mg dose of DX-2930 SC q2wks for 26 weeks.
Rate of Investigator Confirmed Hereditary Angioedema (HAE) Attacks During Day 14 Through Day 182	1.988 Attacks per 4 weeks Interval 1.652 to 2.391	0.445 Attacks per 4 weeks Interval 0.283 to 0.698	0.489 Attacks per 4 weeks Interval 0.326 to 0.734	0.218 Attacks per 4 weeks Interval 0.115 to 0.414

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 40 other events

Deaths: 0 deaths

Lanadelumab (DX-2930) 150 mg Every 4 Weeks

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Lanadelumab (DX-2930) 300 mg Every 4 Weeks

Serious events: 3 serious events

Other events: 26 other events

Deaths: 0 deaths

Lanadelumab (DX-2930) 300 mg Every 2 Weeks

Serious events: 2 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=41 participants at risk Participants received placebo matched to DX-2930 SC q2wks for 26 weeks.	Lanadelumab (DX-2930) 150 mg Every 4 Weeks n=28 participants at risk Participants received 150 mg dose of DX-2930 SC q4wks and matched placebo SC q2wks between DX-2930 doses for 26 weeks.	Lanadelumab (DX-2930) 300 mg Every 4 Weeks n=29 participants at risk Participants received 300 mg dose of DX-2930 SC q4wks and matched placebo SC q2wks between DX-2930 doses for 26 weeks.	Lanadelumab (DX-2930) 300 mg Every 2 Weeks n=27 participants at risk Participants received 300 mg dose of DX-2930 SC q2wks for 26 weeks.
Congenital, familial and genetic disorders Hereditary angioedema	2.4% 1/41 • Number of events 1 • From start of study drug administration up to Day 182 Adverse events were collected over the entire treatment period and were assigned to the treatment group without regard to the type of injection (that is placebo or active drug in the 150 mg q4wk and 300 mg q4wk groups). Number of adverse events were calculated as unique events per System Organ Class (SOC), preferred term (PT), participant and adverse event start date.	0.00% 0/28 • From start of study drug administration up to Day 182 Adverse events were collected over the entire treatment period and were assigned to the treatment group without regard to the type of injection (that is placebo or active drug in the 150 mg q4wk and 300 mg q4wk groups). Number of adverse events were calculated as unique events per System Organ Class (SOC), preferred term (PT), participant and adverse event start date.	0.00% 0/29 • From start of study drug administration up to Day 182 Adverse events were collected over the entire treatment period and were assigned to the treatment group without regard to the type of injection (that is placebo or active drug in the 150 mg q4wk and 300 mg q4wk groups). Number of adverse events were calculated as unique events per System Organ Class (SOC), preferred term (PT), participant and adverse event start date.	3.7% 1/27 • Number of events 1 • From start of study drug administration up to Day 182 Adverse events were collected over the entire treatment period and were assigned to the treatment group without regard to the type of injection (that is placebo or active drug in the 150 mg q4wk and 300 mg q4wk groups). Number of adverse events were calculated as unique events per System Organ Class (SOC), preferred term (PT), participant and adverse event start date.
Infections and infestations Catheter site infection	0.00% 0/41 • From start of study drug administration up to Day 182 Adverse events were collected over the entire treatment period and were assigned to the treatment group without regard to the type of injection (that is placebo or active drug in the 150 mg q4wk and 300 mg q4wk groups). Number of adverse events were calculated as unique events per System Organ Class (SOC), preferred term (PT), participant and adverse event start date.	0.00% 0/28 • From start of study drug administration up to Day 182 Adverse events were collected over the entire treatment period and were assigned to the treatment group without regard to the type of injection (that is placebo or active drug in the 150 mg q4wk and 300 mg q4wk groups). Number of adverse events were calculated as unique events per System Organ Class (SOC), preferred term (PT), participant and adverse event start date.	0.00% 0/29 • From start of study drug administration up to Day 182 Adverse events were collected over the entire treatment period and were assigned to the treatment group without regard to the type of injection (that is placebo or active drug in the 150 mg q4wk and 300 mg q4wk groups). Number of adverse events were calculated as unique events per System Organ Class (SOC), preferred term (PT), participant and adverse event start date.	3.7% 1/27 • Number of events 1 • From start of study drug administration up to Day 182 Adverse events were collected over the entire treatment period and were assigned to the treatment group without regard to the type of injection (that is placebo or active drug in the 150 mg q4wk and 300 mg q4wk groups). Number of adverse events were calculated as unique events per System Organ Class (SOC), preferred term (PT), participant and adverse event start date.
Infections and infestations Pyelonephritis	0.00% 0/41 • From start of study drug administration up to Day 182 Adverse events were collected over the entire treatment period and were assigned to the treatment group without regard to the type of injection (that is placebo or active drug in the 150 mg q4wk and 300 mg q4wk groups). Number of adverse events were calculated as unique events per System Organ Class (SOC), preferred term (PT), participant and adverse event start date.	0.00% 0/28 • From start of study drug administration up to Day 182 Adverse events were collected over the entire treatment period and were assigned to the treatment group without regard to the type of injection (that is placebo or active drug in the 150 mg q4wk and 300 mg q4wk groups). Number of adverse events were calculated as unique events per System Organ Class (SOC), preferred term (PT), participant and adverse event start date.	3.4% 1/29 • Number of events 1 • From start of study drug administration up to Day 182 Adverse events were collected over the entire treatment period and were assigned to the treatment group without regard to the type of injection (that is placebo or active drug in the 150 mg q4wk and 300 mg q4wk groups). Number of adverse events were calculated as unique events per System Organ Class (SOC), preferred term (PT), participant and adverse event start date.	0.00% 0/27 • From start of study drug administration up to Day 182 Adverse events were collected over the entire treatment period and were assigned to the treatment group without regard to the type of injection (that is placebo or active drug in the 150 mg q4wk and 300 mg q4wk groups). Number of adverse events were calculated as unique events per System Organ Class (SOC), preferred term (PT), participant and adverse event start date.
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/41 • From start of study drug administration up to Day 182 Adverse events were collected over the entire treatment period and were assigned to the treatment group without regard to the type of injection (that is placebo or active drug in the 150 mg q4wk and 300 mg q4wk groups). Number of adverse events were calculated as unique events per System Organ Class (SOC), preferred term (PT), participant and adverse event start date.	0.00% 0/28 • From start of study drug administration up to Day 182 Adverse events were collected over the entire treatment period and were assigned to the treatment group without regard to the type of injection (that is placebo or active drug in the 150 mg q4wk and 300 mg q4wk groups). Number of adverse events were calculated as unique events per System Organ Class (SOC), preferred term (PT), participant and adverse event start date.	3.4% 1/29 • Number of events 1 • From start of study drug administration up to Day 182 Adverse events were collected over the entire treatment period and were assigned to the treatment group without regard to the type of injection (that is placebo or active drug in the 150 mg q4wk and 300 mg q4wk groups). Number of adverse events were calculated as unique events per System Organ Class (SOC), preferred term (PT), participant and adverse event start date.	0.00% 0/27 • From start of study drug administration up to Day 182 Adverse events were collected over the entire treatment period and were assigned to the treatment group without regard to the type of injection (that is placebo or active drug in the 150 mg q4wk and 300 mg q4wk groups). Number of adverse events were calculated as unique events per System Organ Class (SOC), preferred term (PT), participant and adverse event start date.
Psychiatric disorders Bipolar ii disorder	0.00% 0/41 • From start of study drug administration up to Day 182 Adverse events were collected over the entire treatment period and were assigned to the treatment group without regard to the type of injection (that is placebo or active drug in the 150 mg q4wk and 300 mg q4wk groups). Number of adverse events were calculated as unique events per System Organ Class (SOC), preferred term (PT), participant and adverse event start date.	0.00% 0/28 • From start of study drug administration up to Day 182 Adverse events were collected over the entire treatment period and were assigned to the treatment group without regard to the type of injection (that is placebo or active drug in the 150 mg q4wk and 300 mg q4wk groups). Number of adverse events were calculated as unique events per System Organ Class (SOC), preferred term (PT), participant and adverse event start date.	3.4% 1/29 • Number of events 1 • From start of study drug administration up to Day 182 Adverse events were collected over the entire treatment period and were assigned to the treatment group without regard to the type of injection (that is placebo or active drug in the 150 mg q4wk and 300 mg q4wk groups). Number of adverse events were calculated as unique events per System Organ Class (SOC), preferred term (PT), participant and adverse event start date.	0.00% 0/27 • From start of study drug administration up to Day 182 Adverse events were collected over the entire treatment period and were assigned to the treatment group without regard to the type of injection (that is placebo or active drug in the 150 mg q4wk and 300 mg q4wk groups). Number of adverse events were calculated as unique events per System Organ Class (SOC), preferred term (PT), participant and adverse event start date.

Other adverse events

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Publication restrictions are in place

Restriction type: OTHER