Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Temporarily halted
Participants planned
25
Countries
1
Sites
1
Complex Regional Pain Syndrome
To evaluate the feasibility and safety of perineural administration of incobotulinumtoxinA (Xeomin) in patients with unilateral CRPS type I or II, in preparation for a future controlled efficacy trial.
Key facts
- Sponsor
- Rigshospitalet
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10]
- Trial duration
- 7 Jan 2026 → ongoing
- Decision date (initial)
- 2025-10-13
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- No
- Funding sources
- Merz Pharmaceutical GmBH
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Others
To evaluate the feasibility and safety of perineural administration of incobotulinumtoxinA (Xeomin) in patients with unilateral CRPS type I or II, in preparation for a future controlled efficacy trial.
Secondary objectives 3
- To monitor for acute flare-up reactions following perineural incobotulinumtoxinA injection as a key feasibility and safety outcome.
- To assess the acceptability of trial procedures and patient burden associated with study participation, including pain diaries, sensory testing, and questionnaires.
- To pilot outcome collection methods (e.g. CRPS severity scoring, patient-reported measures) for their suitability in a future randomized controlled trial.
Conditions and MedDRA coding
Complex Regional Pain Syndrome
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | PT | 10064332 | Complex regional pain syndrome | 100000004852 |
| 21.1 | LLT | 10064334 | Complex regional pain syndrome Type I | 10029205 |
| 28.0 | LLT | 10064335 | Complex regional pain syndrome Type II | 10029205 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Active intervention This study is a single-armed open-label design
|
2 | None | Active: Participants receive 200 units of incobotulinumtoxin-A injected perineurally in the affected limb. |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Participant is 18 years of age or older.
- Participant has a diagnosis of CRPS type I or II affecting one upper or one lower limb which 1) meets the Budapest Research Criteria and 2) has been present for at least 6 months
- CRPS is rated by the participant as their primary pain condition.
- Analgesic treatment, including rescue medications, has been stable for at least one month prior to study entry and will be maintained throughout the study.
- Female participants of childbearing potential agree to use an effective and approved method of contraception during the study period.
- Participant can speak, read, and understand Danish.
Exclusion criteria 12
- Participant has a known allergy to incobotulinumtoxinA (BoNT-A).
- Participant has received any BoNT-A treatment within 3 months prior to study start.
- Participant has a diagnosis of myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis, or other conditions that impair accurate pain assessment.
- Participant has an active infection in the affected limb.
- Participant plans to initiate physical therapy, psychotherapy, or other non-pharmaceutical pain treatments during the study.
- Participant has used topical analgesics (e.g. lidocaine patches) on the affected area within 1 week of study start.
- Participant has been treated with capsaicin patches on the affected area within 3 months of study start.
- Participant has psychiatric comorbidities that, in the investigator’s opinion, may interfere with participation.
- Participant consumes alcohol above the recommended limits set by the Danish Health Authority.
- Participant is actively using illicit drugs.
- Participant is pregnant, breastfeeding, or planning pregnancy during the study period.
- Participant has any other condition or circumstance that the investigator considers incompatible with safe and complete study participation.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Overall feasibility analysis of a full scale trial, based on patient and investigator feedback, recruitment-, inclusion- and, completion- percentages and rates
Secondary endpoints 3
- Documentation of flare-up symptoms post-injection
- Qualiative analysis of patient interviews on treatment, effects, and participation burden.
- Estimates of effect size on pain reduction for use in future power calculations.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
XEOMIN 200 units powder for solution for injection
PRD4392616 · Product
- Active substance
- Clostridium Botulinum Neurotoxin Type a (150KD), Free of Complexing Proteins
- Substance synonyms
- IncobotulinumtoxinA, NT 201, Botulinum toxin type A (150 kD), free from complexing proteins
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- PERINEURAL USE
- Max daily dose
- 200 U unit(s)
- Max total dose
- 200 U unit(s)
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- M03AX01 — BOTULINUM TOXIN
- Marketing authorisation
- PL 29978/0004
- MA holder
- MERZ PHARMACEUTICALS GMBH
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Perineural administration and off-label use (CRPS). No changes to the substance or packaging, apart from labelling for study use (See attached label)
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Rigshospitalet
- Sponsor organisation
- Rigshospitalet
- Address
- Valdemar Hansens Vej 1-23
- City
- Glostrup
- Postcode
- 2600
- Country
- Denmark
Scientific contact point
- Organisation
- Rigshospitalet
- Contact name
- Marc Klee Olsen
Public contact point
- Organisation
- Rigshospitalet
- Contact name
- Marc Klee Olsen
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Region Hovedstaden ORG-100003705
|
Frederiksberg, Denmark | On site monitoring |
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Temporarily halted | 25 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Denmark | 2026-01-07 | 2026-01-07 | 2026-04-09 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 1 · Art. 38 CTR
Temporary halt TH-128350
- Halt date
- 2026-04-09
- Member states concerned
- Denmark
- Publication date
- 2026-04-10
- Reason
- Sponsor decision, Safety related (clinical or pre-clinical results)
- Explanation
- Concerns over safety of perienural injection around the brachial plexus. One reported serious adverse event where, following injection, subject developed traumatic dissection of the internal carotid and vertebral arteries, assumed to be a procedure related complication.
- Follow-up measures
- Halt to recruitment.
- Benefit-risk balance changed
- Yes
- Treatment stopped
- No
Urgent safety measures 1 · Art. 54 CTR
Urgent safety measure US-128352
- Event date
- 2026-04-10
- Submission date
- 2026-04-10
- In response to
- UNEXPECTED
- Member states affected
- Denmark
- Event description
- Internal Carotid and vertebral artery dissection following perineural brachial plexus injection.
- Measures taken
- Halted recruitment and treatment.
Unexpected events 1 · Art. 53 CTR
Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.
Unexpected event UE-128353
- Event date
- 2026-04-06
- Date aware
- 2026-04-08
- Submission date
- 2026-04-10
- Member states affected
- Denmark
- Clinical procedures
- Perineural brachial plexus injection, ultrasound guided.
- Event description
- On 27 March 2026, participant ID 04 in the PINCom study underwent protocol-specified ultrasound-guided perineural administration of 200 IU incobotulinumtoxinA (Xeomin) around the left brachial plexus via a left supraclavicular approach. The procedure was performed according to protocol and without immediate complications. No vascular puncture was observed during the procedure.
In the hours following treatment, the participant developed swelling, discoloration, and local pain at the injection site. At the scheduled Day 5 follow-up visit on 1 April 2026, the participant additionally reported episodic stabbing pain along the left scapular region and worsening of pre-existing CRPS pain and dystonia. With the exception of the CRPS worsening, these symptoms had partially improved spontaneously by Day 5.
At the scheduled Day 10 interview on 8 April 2026, the participant reported progressive symptoms developing after the Day 5 visit, including increasing left-sided neck pain, left-sided headache, and intermittent left-sided ptosis and facial drooping. On this basis, urgent admission to the Department of Neurology, SUH Roskilde, was arranged with suspicion of cervical arterial dissection. The sponsor was informed shortly thereafter.
At admission, the participant was neurologically intact and clinically stable. Non-contrast CT of the brain showed an old lacunar infarct and an incidental top-of-the-basilar aneurysm. CT angiography demonstrated dissection of the left internal carotid artery and left vertebral artery.
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 21 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | PFD_CSS_DK | 1 |
| Protocol (for publication) | PFD_EQ-5D-5L_DK | 1 |
| Protocol (for publication) | PFD_PainDiaryCRPS_DK | 1 |
| Protocol (for publication) | PFD_PainMapping_DK | 1 |
| Protocol (for publication) | PFD_PCS_DK | 1 |
| Protocol (for publication) | PFD_PGI-C_DK | 1 |
| Protocol (for publication) | PFD_PROMIS29_DK | 1 |
| Protocol (for publication) | PFD_PSEQ-DK | 1 |
| Protocol (for publication) | PFD_SF-MPQ-2_DK | 1 |
| Protocol (for publication) | Protocol_EN | 1.2.4 |
| Recruitment arrangements (for publication) | Non-substantial amenmendt 1 | 1 |
| Recruitment arrangements (for publication) | Recruitment arrangements | 1.1 |
| Recruitment arrangements (for publication) | Recruitment poster | 1.1 |
| Recruitment arrangements (for publication) | Recruitment poster (reupload) | 1.1 |
| Subject information and informed consent form (for publication) | Dine rettigheder som forsgsperson i forsg med medicin _ De Videnskabsetiske Komiteer | 1 |
| Subject information and informed consent form (for publication) | L1_ ICF all subjects | 1 |
| Subject information and informed consent form (for publication) | SIS General subject information sheet Clean | 1.3 |
| Subject information and informed consent form (for publication) | SIS General subject information sheet_RFI 5 TC | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2 SmPC Xeomin 200 U | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ Addendum to SmPC Xeomin perineural administration | 1 |
| Synopsis of the protocol (for publication) | Protocol_Synopsis_DK | 1.2 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-07-04 | Denmark | Acceptable 2025-09-19
|
2025-10-13 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2026-02-02 | Denmark | Acceptable 2025-09-19
|
2026-02-02 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2026-02-25 | Denmark | Acceptable 2025-09-19
|
2026-02-25 |