BMN 701 Phase 3 in rhGAA Exposed Subjects With Late Onset Pompe Disease (INSPIRE Study)

• Sponsor: BioMarin Pharmaceutical (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01924845
• Collaborator: (none)
• Enrollment: 24
• Locations: 22
• Arm: 1
• Actual Duration (Months): 29.4
• Patients Per Site: 1.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Study 701-301 is a single-arm, open-label, switchover study in patients with late-onset Pompe disease who have been receiving treatment with recombinant human acid alpha-glucosidase (rhGAA) for 48 weeks or longer. Ambulatory patients who have mild to moderate respiratory impairment will switch directly to receive BMN 701 20 mg/kg by IV infusion every other week. All participants will receive active drug. No dose of existing therapy will be missed - experimental drug is started immediately.

Condition or Disease	Intervention/Treatment	Phase
Late-onset Pompe Disease	Drug: BMN 701	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Switchover Study of the Efficacy and Safety of BMN 701 (GILT-tagged Recombinant Human GAA) and Long-Term Study for Extended Treatment in rhGAA Exposed Subjects With Late-onset Pompe Disease
• Actual Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: Sep 12, 2016
• Actual Study Completion Date: Sep 12, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BMN 701 20 mg/kg BMN 701 IV Infusion 20mg/kg every 2 weeks for 24 weeks followed by an optional extension of 240 weeks (total duration of therapy 264 weeks)	Drug: BMN 701; BMN 701 20 mg/kg for intravenous administration over approximately 4 hours every 2 weeks over a 24-week Treatment Period (total of 13 doses), and every 2 weeks over a 240-week Extension Period (up to 120 additional doses).

Outcome Measures

Primary Outcome Measures

1. Percent Predicted Maximum Inspiratory Pressure (MIP) [Baseline, Week 24]

   Pulmonary function test: Percent Predicted Maximum Inspiratory Pressure

Secondary Outcome Measures

1. Percent Predicted Maximum Expiratory Pressure (MEP) [Baseline, Week 24]

   Pulmonary function test: Percent Predicted Maximum Expiratory Pressure

2. 6 Minute Walk Test (Meters) [Baseline, Week 24]

   Distance walked within 6 minutes

3. Percent Predicted Upright Forced Vital Capacity (FVC) [Baseline, Week 24]

   Pulmonary function test: Percent Predicted Upright Forced Vital Capacity

4. Number of Participants With Non-Serious AEs [Baseline through Week 24 +4 weeks follow-up]

   Number of participants with non-serious Adverse Events. Data is taken at final time point of Week 24, compared to baseline. For full AE data, please see AE section.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Willing and able to provide written informed consent, after the nature of the study has been explained, and prior to any study-related procedures.

• Diagnosed with late-onset Pompe disease based on 2 currently or previously documented GAA gene mutations, and endogenous GAA activity <75% of the lower limit of the normal adult range reported by the testing laboratory, as assessed by dried blood spot or whole blood assay.

• Has received prior treatment with commercial rhGAA as defined by ALL of the following:

1. has received treatment with commercial rhGAA for ≥ 48 weeks (but no more than 20% of the study population can have received treatment for ≥ 6 years).

2. has received > 80% of all scheduled treatments in the prior 48 weeks and ≥ 4 out of the prior 6 scheduled treatments.

3. has received and completed the last two infusions without a drug-related adverse event resulting in dose interruption.

4. has received last treatment of commercial rhGAA ≥ 10 and ≤ 31 days prior to anticipated initiation of treatment with BMN 701.

• ≥ 18 years of age at the time of enrollment in the study.

• Sexually active subjects must be willing to use two known effective methods of contraception while participating in the study and for at least 4 months following the last dose of BMN 701.

• Females of childbearing potential must have a negative pregnancy test at Screening and Baseline visits and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to Screening, or who have had total hysterectomy.

• Has ≥ 30% predicted upright FVC and < 80% predicted upright FVC.

• Has ≤60% predicted MIP.

• Is able to ambulate ≥75 meters and ≤500 meters on the 6MWT conducted during the Screening visit (use of assistive devices such as walker, cane, or crutches, is permitted with consistent use throughout the study).

• Is willing and able to comply with all study procedures.

Exclusion Criteria:

• Use of any investigational product or investigational medical device within 4 weeks prior to Screening, or requirement for any investigational agent other than BMN 701 prior to completion of at least the first 24 weeks of all scheduled study assessments.

• Received any investigational medication for Pompe disease within the prior 12 months.

• Has a diagnosis of diabetes and/or is currently being treated with or anticipated to require treatment with hypoglycemic agents during the course of the study.

• Has been treated with any immunosuppressive medication other than glucocorticosteroids within the prior 12 months.

• Requires noninvasive ventilatory support while awake and in the upright position.

• Has previously been enrolled to this study.

• Breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.

• Concurrent disease, medical condition, or extenuating circumstance that, in the opinion of the Investigator, might compromise subject safety, study treatment compliance and completion of the study, or the integrity of the data collected for the study.

• Has known hypersensitivity to BMN 701 or its excipients.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Neuromuscular Research Centre	Phoenix	Arizona	United States	85028
2	University of California, Irvine	Orange	California	United States	92868
3	University of Florida	Gainesville	Florida	United States	32610
4	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
5	Washington University	Saint Louis	Missouri	United States	36110
6	Duke University Medical Center	Durham	North Carolina	United States	27710
7	The Ohio State University - Wexner Medical Center	Columbus	Ohio	United States	43210
8	University of Utah	Salt Lake City	Utah	United States	84132
9	Antwerp University Hospital (UZA)	Edegem		Belgium
10	Hôpital Raymond Poincaré	Garches		France	92380
11	CHU de la Timone	Marseille		France	13005
12	Villa Metabolica, ZKJM MC University Mainz	Mainz		Germany
13	Klinikum der Universität München	München		Germany
14	Universitätsklinikum Münster	Münster		Germany	48149
15	Azienda Ospedaliera Universitaria Policlinico "G. Martino" - Messina	Messina	ME	Italy	98125
16	Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta	Milano		Italy	20133
17	Erasmus MC University Medical Center	Rotterdam		Netherlands	3015 GJ
18	Centro Hospitalar de Sao Joao, EPE	Porto		Portugal	4200-319
19	University Hospital Birmingham	Birmingham		United Kingdom
20	Royal Free Hospital	London		United Kingdom	NW3 2QG
21	National Hospital for Neurology and Neurosurgery	London		United Kingdom
22	Salford Royal NHS Foundation Trust	Salford		United Kingdom	M5 5AP

Sponsors and Collaborators

• BioMarin Pharmaceutical

Investigators

• Study Director: Study Monitor, BioMarin Pharmaceutical

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: BioMarin Pharmaceutical
• ClinicalTrials.gov Identifier: NCT01924845
• Other Study ID Numbers: 701-301; 2013-001768-48
• First Posted: Aug 19, 2013
• Last Update Posted: Jun 14, 2018
• Last Verified: Jun 1, 2018

• Additional relevant MeSH terms: Glycogen Storage Disease Type II

Study Results

Participant Flow

Pre-assignment Detail	The study consisted of a 31-day Screening and Baseline Period (26-day Screening Period, a 5-day Baseline/Enrollment Period), a 24-week Treatment Period, and a 30-day Safety Follow-up Period. Following the Screening and Baseline assessments, qualified subjects were enrolled in the study.

Arm/Group Title	BMN 701 20 mg/kg
Arm/Group Description	BMN 701 20 mg/kg
Period Title: Overall Study
STARTED	24
COMPLETED	18
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	BMN 701 20 mg/kg
Arm/Group Description	BMN 701 20 mg/kg
Overall Participants	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.9 (13.27)
Age, Customized (Count of Participants)
18-65	22 91.7%
> 65	2 8.3%
Sex: Female, Male (Count of Participants)
Female	12 50%
Male	12 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	24 100%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	24 100%
Other	0 0%
Region of Enrollment (Count of Participants)
Belgium	1 4.2%
Germany	9 37.5%
United Kingdom	7 29.2%
United States	7 29.2%

Outcome Measures

1. Primary Outcome

Title	Percent Predicted Maximum Inspiratory Pressure (MIP)
Description	Pulmonary function test: Percent Predicted Maximum Inspiratory Pressure
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Please note the Overall Number of Participants reflects the number of patients in the Analysis Population, while the Number Analyzed of patients at specific visit in the Outcome Measure Table reflects the participants who had data at that visit .

Arm/Group Title	BMN701 20 mg/kg
Arm/Group Description	BMN701 20 mg/kg
Measure Participants	18
Baseline	50.0 (17.5)
Change from Baseline to Week 24	2.2 (8.3)

2. Secondary Outcome

Title	Percent Predicted Maximum Expiratory Pressure (MEP)
Description	Pulmonary function test: Percent Predicted Maximum Expiratory Pressure
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Please note the Overall Number of Participants reflects the number of patients in the Analysis Population, while the Number Analyzed of patients at specific visit in the Outcome Measure Table reflects the participants who had data at that visit .

Arm/Group Title	BMN701 20 mg/kg
Arm/Group Description	BMN701 20 mg/kg
Measure Participants	18
Baseline	38.9 (12.3)
Change from Baseline to Week 24	3.1 (8.7)

3. Secondary Outcome

Title	6 Minute Walk Test (Meters)
Description	Distance walked within 6 minutes
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Please note the Overall Number of Participants reflects the number of patients in the Analysis Population, while the Number Analyzed of patients at specific visit in the Outcome Measure Table reflects the participants who had data at that visit .

Arm/Group Title	BMN701 20 mg/kg
Arm/Group Description	BMN701 20 mg/kg
Measure Participants	17
Baseline	345.8 (95.3)
Change from Baseline to Week 24	26.1 (40.6)

4. Secondary Outcome

Title	Percent Predicted Upright Forced Vital Capacity (FVC)
Description	Pulmonary function test: Percent Predicted Upright Forced Vital Capacity
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set. Please note the Overall Number of Participants reflects the number of patients in the Analysis Population, while the Number Analyzed of patients at specific visit in the Outcome Measure Table reflects the participants who had data at that visit .

Arm/Group Title	BMN701 20 mg/kg
Arm/Group Description	BMN701 20 mg/kg
Measure Participants	18
Baseline	60.7 (15.1)
Change from Baseline to Week 24	-3.7 (4.4)

5. Secondary Outcome

Title	Number of Participants With Non-Serious AEs
Description	Number of participants with non-serious Adverse Events. Data is taken at final time point of Week 24, compared to baseline. For full AE data, please see AE section.
Time Frame	Baseline through Week 24 +4 weeks follow-up

Outcome Measure Data

Analysis Population Description

Full Analysis Set.

Arm/Group Title	BMN701 20 mg/kg
Arm/Group Description	BMN701 20 mg/kg
Measure Participants	24
Count of Participants [Participants]	23 95.8%

Adverse Events

Time Frame	28 weeks (24 weeks trial + 4 weeks follow up)
Arm/Group Title	BMN 701 20 mg/kg
Arm/Group Description	BMN 701 20 mg/kg
All Cause Mortality
	BMN 701 20 mg/kg
	Affected / at Risk (%)	# Events
Total	0/24 (0%)
Serious Adverse Events
	BMN 701 20 mg/kg
	Affected / at Risk (%)	# Events
Total	10/24 (41.7%)
Cardiac disorders
Atrial fibrillation	1/24 (4.2%)	1
Gastrointestinal disorders
Abdominal pain upper	1/24 (4.2%)	2
Immune system disorders
Anaphylactic reaction	1/24 (4.2%)	1
Injury, poisoning and procedural complications
Fall	1/24 (4.2%)	2
Investigations
Blood creatine phosphokinase increased	1/24 (4.2%)	1
Metabolism and nutrition disorders
Hypoglycaemia	1/24 (4.2%)	1
Musculoskeletal and connective tissue disorders
Pain in extremity	1/24 (4.2%)	1
Respiratory, thoracic and mediastinal disorders
Pneumothorax	1/24 (4.2%)	1
Respiratory failure	1/24 (4.2%)	1
Skin and subcutaneous tissue disorders
Erythema nodosum	1/24 (4.2%)	1
Vascular disorders
Hypertension	1/24 (4.2%)	1
Other (Not Including Serious) Adverse Events
	BMN 701 20 mg/kg
	Affected / at Risk (%)	# Events
Total	23/24 (95.8%)
Cardiac disorders
Palpitations	4/24 (16.7%)	5
Gastrointestinal disorders
Abdominal discomfort	2/24 (8.3%)	2
Abdominal distension	2/24 (8.3%)	2
Abdominal pain upper	2/24 (8.3%)	3
Diarrhoea	5/24 (20.8%)	8
Nausea	8/24 (33.3%)	22
Vomiting	4/24 (16.7%)	7
General disorders
Chest discomfort	2/24 (8.3%)	3
Chills	4/24 (16.7%)	6
Fatigue	5/24 (20.8%)	8
Pain	2/24 (8.3%)	2
Infections and infestations
Lower respiratory tract infection	3/24 (12.5%)	4
Nasopharyngitis	4/24 (16.7%)	5
Pharyngitis	2/24 (8.3%)	2
Upper respiratory tract infection	2/24 (8.3%)	2
Viral infection	3/24 (12.5%)	3
Injury, poisoning and procedural complications
Fall	5/24 (20.8%)	6
Infusion related reaction	2/24 (8.3%)	2
Metabolism and nutrition disorders
Hypoglycaemia	16/24 (66.7%)	165
Musculoskeletal and connective tissue disorders
Arthralgia	2/24 (8.3%)	5
Back pain	5/24 (20.8%)	12
Musculoskeletal pain	4/24 (16.7%)	4
Myalgia	3/24 (12.5%)	5
Neck pain	2/24 (8.3%)	2
Pain in extremity	5/24 (20.8%)	6
Nervous system disorders
Dizziness	8/24 (33.3%)	12
Headache	13/24 (54.2%)	50
Lethargy	2/24 (8.3%)	2
Tremor	4/24 (16.7%)	5
Psychiatric disorders
Insomnia	2/24 (8.3%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnoea	6/24 (25%)	12
Dyspnoea exertional	2/24 (8.3%)	4
Nasal congestion	4/24 (16.7%)	4
Nasal obstruction	2/24 (8.3%)	3
Oropharyngeal pain	5/24 (20.8%)	5
Skin and subcutaneous tissue disorders
Cold sweat	2/24 (8.3%)	3
Hyperhidrosis	2/24 (8.3%)	2
Pruritus	2/24 (8.3%)	4
Rash	2/24 (8.3%)	2
Vascular disorders
Hypotension	3/24 (12.5%)	3

Limitations/Caveats

Complete efficacy analyses were not able to be completed due to early study termination; however, efficacy results from interim analysis at week 24 are available, and thus have been reported.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.