Efficacy and safety of early intramuscular botulinum toxin injections in the prevention of shoulder deformity in infants with obstetric brachial plexus palsy: a randomized double-blind multicenter controlled trial. POPBTOX

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Regional Et Universitaire De Brest

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Decision date (initial)

2025-01-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Hospital clinical research program - PHRC

External identifiers

EU CT number

2024-520391-10-01

EudraCT number

2015-001402-34

ClinicalTrials.gov

NCT03198702

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The main aim of this study was to evaluate the efficacy of botulinum toxin injections into the shoulder internal rotator muscles at 12 months of age in preventing worsening of posterior glenohumeral joint subluxation in infants between 11 and 18 months of age, compared with the Sham group (control).

Secondary objectives 5

1. Evaluate the efficacy of botulinum toxin injections versus Sham in preventing worsening of glenoid retroversion, as well as in preventing three-dimensional deformity
2. Evaluate the effect of injections versus Sham in improving active and passive joint amplitudes and function.
3. Confirm the good clinical tolerance of this treatment.
4. Assess the impact of injections on the targeted muscles in terms of trophicity and fibrous and fatty infiltration, as well as on muscular balance in the shoulder with POPB.
5. Find out whether this treatment will eventually lead to a change in the frequency and type of surgical management.

Conditions and MedDRA coding

Obstetrical Brachial Plexus Palsy

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Male or female babies with unilateral POPB.
2. More than 10 months and less than 11 months of age.
3. Presenting, on the affected side, one of the following 2 risk factors for posterior subluxation of the humeral head: 1/ A limitation of passive joint amplitude in external rotation on the shoulder with respect to the contralateral side of at least 10°. 2/ Active Movement Scale (AMS) score strictly below 6 for external rotation, shoulder abduction, elbow flexion or supination.
4. With consent of adult parents.

Exclusion criteria 7

1. Bilateral POPB
2. Microsurgical management or scheduled secondary muscle surgery between 12 and 18 months of age.
3. Non-inclusion related to botulinum toxin use (hypersensitivity to botulinum toxin or excipients, myasthenia).
4. Classic contraindications to MRI: pacemaker, metal implantable devices, ocular foreign bodies, etc.
5. Impossibility of performing an MRI in a Pediatric Day Hospital, due to contraindications linked to the sedation protocol or organizational constraints.
6. Parent(s) unable to give informed consent.
7. Minor parent(s)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Evolution of the percentage of posterior migration of the humeral head measured in MRI on an axial section, between 11 months (before botulinum toxin injection at 12 months) and 18 months (6 months after injection) of age.

Secondary endpoints 8

1. 2D glenoid evolution measured in MRI on an axial slice (1st secondary objective)
2. Evolution of the glenoid version and three-dimensional humeral head migration on MRI (1st secondary objective)
3. Changes in passive joint amplitudes (2nd secondary objective)
4. Evolution of the AMS (Active Movement Scale) (2nd secondary objective)
5. Progression of mini-AHA (mini-Assistive Hand Assessment) score (2nd secondary objective)
6. Assessment of the number of non-serious and serious adverse events (3rd secondary objective)
7. Assessment of trophicity (muscle volume) and fatty infiltration of injected muscles (supraspinatus, infraspinatus and lesser round, subscapularis, greater round, pectoralis major, deltoid, greater dorsalis) (4th secondary objective).
8. Surgical management of the children included in each group will be recorded post-study during medical follow-up (routine clinical practice) up to the 10th year of life after the blind has been lifted (5th secondary objective).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Regional Et Universitaire De Brest

Sponsor organisation

Centre Hospitalier Regional Et Universitaire De Brest

Address

2 Avenue Marechal Foch

City

Brest

Postcode

29200

Country

France

Scientific contact point

Organisation

Centre Hospitalier Regional Et Universitaire De Brest

Contact name

Sylvain BROCHARD

Public contact point

Organisation

Centre Hospitalier Regional Et Universitaire De Brest

Contact name

Sylvain BROCHARD

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications