Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia (NCT NCT03197766)

NCT ID: NCT03197766

Last Updated: 2022-03-02

Results Overview

AGV at a Post-baseline Visit is defined as \[(Height at Post-baseline Visit - Height at Baseline)/(Date of Post-baseline Visit - Date of Baseline Assessment)\] x 365.25 AGV at Baseline is defined as \[(Height at Baseline - last height measurement in Study 111-901 at least 6 months prior to Baseline)/(Date of Baseline Assessment - Date of last height measurement in Study 111-901 at least 6 months prior to Baseline)\] x 365.25

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

121 participants

Primary outcome timeframe

At Baseline and Week 52

Results posted on

2022-03-02

Participant Flow

This was a multi-centre study conducted by 24 principal investigators at 24 study centers in 7 countries

A total of 121 subjects were enrolled into the study, 119 subjects completed and 2 subjects withdrew from the study.

Participant milestones

Participant milestones
Measure	BMN 111 - 15 μg/kg BMN 111: Subcutaneous injection of 15 μg/kg of BMN 111 daily	Placebo Placebo: Subcutaneous injection of placebo daily
Overall Study STARTED	60	61
Overall Study COMPLETED	58	61
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	BMN 111 - 15 μg/kg BMN 111: Subcutaneous injection of 15 μg/kg of BMN 111 daily	Placebo Placebo: Subcutaneous injection of placebo daily
Overall Study Withdrawal by Subject	2	0

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BMN 111 - 15 μg/kg n=60 Participants BMN 111: Subcutaneous injection of 15 μg/kg of BMN 111 daily	Placebo n=61 Participants Placebo: Subcutaneous injection of placebo daily	Total n=121 Participants Total of all reporting groups
Age, Continuous	8.35 years STANDARD_DEVIATION 2.43 • n=5 Participants	9.06 years STANDARD_DEVIATION 2.47 • n=7 Participants	8.71 years STANDARD_DEVIATION 2.47 • n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants	28 Participants n=7 Participants	57 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	33 Participants n=7 Participants	64 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	59 Participants n=5 Participants	55 Participants n=7 Participants	114 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	45 Participants n=5 Participants	41 Participants n=7 Participants	86 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian-Other	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian-Japanese	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Race · Multiple	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Annualized Growth Velocity (AGV)	4.26 cm/year STANDARD_DEVIATION 1.53 • n=5 Participants	4.06 cm/year STANDARD_DEVIATION 1.20 • n=7 Participants	4.16 cm/year STANDARD_DEVIATION 1.37 • n=5 Participants
Height Z-Score	-5.13 Z-score STANDARD_DEVIATION 1.11 • n=5 Participants	-5.14 Z-score STANDARD_DEVIATION 1.07 • n=7 Participants	-5.13 Z-score STANDARD_DEVIATION 1.09 • n=5 Participants
Upper to Lower Body Segment Ratio	1.98 Ratio STANDARD_DEVIATION 0.20 • n=5 Participants	2.01 Ratio STANDARD_DEVIATION 0.21 • n=7 Participants	2.00 Ratio STANDARD_DEVIATION 0.20 • n=5 Participants

PRIMARY outcome

Timeframe: At Baseline and Week 52

Population: Analysis were performed on the Full Analysis Set (FAS) which included all randomized subjects with a signed informed consent

Outcome measures

Outcome measures
Measure	BMN 111 - 15 μg/kg n=60 Participants BMN 111: Subcutaneous injection of 15 μg/kg of BMN 111 daily	Placebo n=61 Participants Placebo: Subcutaneous injection of placebo daily
Change From Baseline in Annualized Growth Velocity (AGV) at Week 52	1.71 cm/year Interval 1.4 to 2.01	0.13 cm/year Interval -0.18 to 0.45

SECONDARY outcome

Timeframe: At baseline and Week 52

Population: Analysis were performed on the Full Analysis Set (FAS) which included all randomized subjects with a signed informed consent.

Z-Scores were derived using age-sex specific reference data (means and SDS) for average stature children per the Centers for Disease Control and Prevention. A height Z score of 0 would indicate that the subject's height is equal to the mean height for the average stature population of the same sex and age. A positive height Z score indicates that the subjects height is above the mean height for the average stature population of the same sex and age, whilst a negative height Z score indicates that the subjects height is below the mean height for the average stature population of the same sex and age. To conclude if the height Z score increases then this means the height deficit has decreased.

Outcome measures

Outcome measures
Measure	BMN 111 - 15 μg/kg n=60 Participants BMN 111: Subcutaneous injection of 15 μg/kg of BMN 111 daily	Placebo n=61 Participants Placebo: Subcutaneous injection of placebo daily
Change From Baseline in Height Z-score at Week 52	0.27 Z-Score Interval 0.18 to 0.36	-0.01 Z-Score Interval -0.1 to 0.09

SECONDARY outcome

Timeframe: At baseline and Week 52

Population: Analysis were performed on the Full Analysis Set (FAS) which included all randomized subjects with a signed informed consent

Evaluate change from baseline in mean upper:lower segment body ratio in subjects treated with BMN 111 compared with control subjects in the placebo group at 52 weeks

Outcome measures

Outcome measures
Measure	BMN 111 - 15 μg/kg n=60 Participants BMN 111: Subcutaneous injection of 15 μg/kg of BMN 111 daily	Placebo n=61 Participants Placebo: Subcutaneous injection of placebo daily
Change From Baseline in Upper to Lower Segment Body Ratio at Week 52	-0.03 Ratio Interval -0.06 to 0.0	-0.02 Ratio Interval -0.05 to 0.01

SECONDARY outcome

Timeframe: Up to Week 56

Population: The Safety Population was defined as all subjects in the FAS who received at least one dose of double-blind BMN 111 or placebo in this study.

AEs with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included. serious adverse event (SAE)

Outcome measures

Outcome measures
Measure	BMN 111 - 15 μg/kg n=60 Participants BMN 111: Subcutaneous injection of 15 μg/kg of BMN 111 daily	Placebo n=61 Participants Placebo: Subcutaneous injection of placebo daily
Summary of Subjects Experiencing Adverse Events (AEs) During Treatment Subjects who died	0 participants	0 participants
Summary of Subjects Experiencing Adverse Events (AEs) During Treatment Subjects with any AE	59 participants	60 participants
Summary of Subjects Experiencing Adverse Events (AEs) During Treatment Subjects with any SAE	3 participants	4 participants
Summary of Subjects Experiencing Adverse Events (AEs) During Treatment Subjects with any treatment-related AE	53 participants	51 participants

Adverse Events

BMN 111 - 15 μg/kg

Serious events: 3 serious events

Other events: 59 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 60 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	BMN 111 - 15 μg/kg n=60 participants at risk BMN 111: Subcutaneous injection of 15 μg/kg of BMN 111 daily	Placebo n=61 participants at risk Placebo: Subcutaneous injection of placebo daily
Infections and infestations Influenza	1.7% 1/60 • Up to Week 56 A treatment-emergent Adverse Event (TEAE) is any Adverse Event with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included. The Safety Population is defined as all subjects in the FAS who received at least one dose of double-blind BMN 111 or placebo in this study	0.00% 0/61 • Up to Week 56 A treatment-emergent Adverse Event (TEAE) is any Adverse Event with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included. The Safety Population is defined as all subjects in the FAS who received at least one dose of double-blind BMN 111 or placebo in this study
Infections and infestations Appendicitis	0.00% 0/60 • Up to Week 56 A treatment-emergent Adverse Event (TEAE) is any Adverse Event with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included. The Safety Population is defined as all subjects in the FAS who received at least one dose of double-blind BMN 111 or placebo in this study	1.6% 1/61 • Up to Week 56 A treatment-emergent Adverse Event (TEAE) is any Adverse Event with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included. The Safety Population is defined as all subjects in the FAS who received at least one dose of double-blind BMN 111 or placebo in this study
Injury, poisoning and procedural complications Radius fracture	1.7% 1/60 • Up to Week 56 A treatment-emergent Adverse Event (TEAE) is any Adverse Event with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included. The Safety Population is defined as all subjects in the FAS who received at least one dose of double-blind BMN 111 or placebo in this study	0.00% 0/61 • Up to Week 56 A treatment-emergent Adverse Event (TEAE) is any Adverse Event with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included. The Safety Population is defined as all subjects in the FAS who received at least one dose of double-blind BMN 111 or placebo in this study
Respiratory, thoracic and mediastinal disorders Adenoidal hypertrophy	1.7% 1/60 • Up to Week 56 A treatment-emergent Adverse Event (TEAE) is any Adverse Event with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included. The Safety Population is defined as all subjects in the FAS who received at least one dose of double-blind BMN 111 or placebo in this study	1.6% 1/61 • Up to Week 56 A treatment-emergent Adverse Event (TEAE) is any Adverse Event with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included. The Safety Population is defined as all subjects in the FAS who received at least one dose of double-blind BMN 111 or placebo in this study
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	1.7% 1/60 • Up to Week 56 A treatment-emergent Adverse Event (TEAE) is any Adverse Event with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included. The Safety Population is defined as all subjects in the FAS who received at least one dose of double-blind BMN 111 or placebo in this study	0.00% 0/61 • Up to Week 56 A treatment-emergent Adverse Event (TEAE) is any Adverse Event with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included. The Safety Population is defined as all subjects in the FAS who received at least one dose of double-blind BMN 111 or placebo in this study
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/60 • Up to Week 56 A treatment-emergent Adverse Event (TEAE) is any Adverse Event with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included. The Safety Population is defined as all subjects in the FAS who received at least one dose of double-blind BMN 111 or placebo in this study	1.6% 1/61 • Up to Week 56 A treatment-emergent Adverse Event (TEAE) is any Adverse Event with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included. The Safety Population is defined as all subjects in the FAS who received at least one dose of double-blind BMN 111 or placebo in this study
Nervous system disorders Intracranial pressure increased	0.00% 0/60 • Up to Week 56 A treatment-emergent Adverse Event (TEAE) is any Adverse Event with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included. The Safety Population is defined as all subjects in the FAS who received at least one dose of double-blind BMN 111 or placebo in this study	1.6% 1/61 • Up to Week 56 A treatment-emergent Adverse Event (TEAE) is any Adverse Event with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included. The Safety Population is defined as all subjects in the FAS who received at least one dose of double-blind BMN 111 or placebo in this study
Nervous system disorders Spinal cord compression	0.00% 0/60 • Up to Week 56 A treatment-emergent Adverse Event (TEAE) is any Adverse Event with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included. The Safety Population is defined as all subjects in the FAS who received at least one dose of double-blind BMN 111 or placebo in this study	1.6% 1/61 • Up to Week 56 A treatment-emergent Adverse Event (TEAE) is any Adverse Event with onset or worsening after the initiation of study drug and up to 30 days after study drug discontinuation were included. The Safety Population is defined as all subjects in the FAS who received at least one dose of double-blind BMN 111 or placebo in this study

Other adverse events

Additional Information

Alice Huntsman Labed

BioMarin Pharmaceutical Inc.

Phone: +44 207 4203392

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER