Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruitment ended
Participants planned
20
Countries
1
Sites
2
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
To evaluate feasibility and safety of daratumumab subcutaneous injections in patients with moderate to severe ME/CFS.
Key facts
- Sponsor
- Helse Bergen HF
- Participant type
- Patients
- Age range
- 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Immune System Diseases [C20]
- Trial duration
- 29 Apr 2022 → ongoing
- Decision date (initial)
- 2024-07-09
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- ME-nettverket i Norge · Fokus på ME · MEandYou · The Norwegian ME Association
External identifiers
- EU CT number
- 2024-512500-19-00
- EudraCT number
- 2022-000281-18
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety
To evaluate feasibility and safety of daratumumab subcutaneous injections in patients with moderate to severe ME/CFS.
Secondary objectives 1
- Efficacy, measured by changes in secondary end points
Conditions and MedDRA coding
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 26.1 | LLT | 10028414 | Myalgic encephalomyelitis | 10021881 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- ME/CFS according to Canadian consensus criteria; moderate to severe disease
- Age 18 to 65 years
- Signed informed consent
- At least two years disease duration
- Defined onset of ME/CFS, e.g. after infection
- Baseline Natural Killer (NK) cell count >130 x 10^6/L
Exclusion criteria 14
- Chronic fatigue conditions not fulfilling Canadian consensus criteria
- Age under 18 or over 65 years
- Mild or mild-moderate ME/CFS
- Very severe ME/CFS
- Participation in clinical intervention trial aimed at ME/CFS within two years before inclusion
- Known multi-allergy with clinically assessed risk for hypersensitivity to daratumumab
- Known contraindication to daratumumab
- Significant comorbidity with reduced organ function (kidney, liver, heart, pulmonary)
- Previous long-term systemic treatment with immunosuppressants the last two years, excluding short steroid courses in e.g. obstructive lung disease
- Chronic infections, including chronic hepatitis B or C, HIV, or other relevant infection
- Previous or concomitant malignant disease, except basal carcinoma of the skin, or carcinoma in situ in the uterine cervix.
- Pregnancy or lactation
- Inability to comply with protocol including follow-up
- Endogenous depression
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Safety and tolerability as measured by treatment-emergent adverse events.
Secondary endpoints 4
- Changes in SF36 domain scores including Physical Function and Bodily pain, from the baseline/run-in period through 40 weeks' follow-up from start of intervention
- Changes in DSQ-SF scores, from the baseline/run-in period through 40 weeks' follow-up from start of intervention
- Changes in patient-reported physical function, from the baseline/run-in period through 40 weeks' follow-up from start of intervention
- Changes in steps per 24 hours, from the baseline/run-in period through 40 weeks' follow-up from start of intervention
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
DARZALEX 1800 mg solution for injection
PRD8157846 · Product
- Active substance
- Daratumumab
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 1800 mg milligram(s)
- Max total dose
- 12600 mg milligram(s)
- Max treatment duration
- 52 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01FC01 — -
- Marketing authorisation
- EU/1/16/1101/004
- MA holder
- JANSSEN-CILAG INTERNATIONAL NV
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Helse Bergen HF
- Sponsor organisation
- Helse Bergen HF
- Address
- Haukelandsveien 22
- City
- Bergen
- Postcode
- 5021
- Country
- Norway
Scientific contact point
- Organisation
- Helse Bergen HF
- Contact name
- Øystein Fluge
Public contact point
- Organisation
- Helse Bergen HF
- Contact name
- Øystein Fluge
Locations
1 EU/EEA country · 2 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Norway | Ongoing, recruitment ended | 20 | 2 |
| 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 |
|---|---|---|---|---|---|
| Norway | 2022-04-29 | 2022-06-03 | 2025-06-01 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Serious breaches 1 · Art. 52 CTR
Serious breach SB-54844
- Sponsor became aware
- 2024-10-21
- Date of breach
- 2024-09-09
- Submission date
- 2024-10-30
- Member states concerned
- Norway
- Categories
- Regulation, Protocol
- Areas impacted
- Subject rights, Subject safety
- Benefit-risk balance changed
- Yes
- Description
- IMP temperature excursions: Individual IMP vials have been temporarily stored in the Oncology outpatient clinic's medical cabinet, in transit from the pharmacy, before administration. The drug refrigerator was fitted with temperature sensors and sensor alarms. On routine extraction of temperature reports for study file, study nurse found irregularities in the reported temperature for the drug refrigerator at the clinic. Temperature excursions dated back to August 15th. No alarm had been triggered, and the temperature display unit on the refrigerator showed 4 to 6 degrees celcius.
Two study patients received their 7th and final injection during this time. One patient received a vial which had been stored locally for three days, from 9-12 Sept. Due to delays in patient treatment (intercurrent infection), vial no. 2 had been stored in the clinic for 22 days, from 23 Sept to 12 Oct. Both patients had been routinely observed for two hours after injections and subsequently followed up with telephone consultations. Neither reported any side effects or anything out of the ordinary.
No further treatments are planned in the trial. - Sponsor actions
- The head of clinic received notification of the irregularities on 17.10.24. As no alarm had been triggered, it was first believed to be a fault in the reporting unit; however, further investigations revealed ongoing temperature excursions. Sponsor received notification of the breach and that two vials of IMP were involved, on 21.10.
Immediate actions taken by study team:
- Identified the involved patients, vials and timepoints.
- Confirmed that patients had not reported any side effects or anything out of the ordinary after injections. Informed patients of the incident.
- Reached out to department pharmacist who contacted pharmaceutical company and is presently investigating any potential consequences for patients. We are awaiting her conclusions.
- Reported the breach in the hospital incident reporting system.
- Contribute to the investigations (ongoing) conducted by the Oncology department and hospital pharmacy.
Actions taken by department:
- Refrigerator emptied and all remaining drugs quarantined (no IMP at this time). Use of the faulty unit discontinued.
- Alerted technical and IT departments. Conclusions so far: The technical department recommends replacement rather than repair of faulty unit. A new alarm had been fitted in January 2024, but had not been activated correctly by the Oncology dept. Sensors and alarm on new unit must be installed and monitored closely both locally and by central operating facility.
- Identified patients, initiated investigations/assessment (with hospital pharmacist and pharmaceutical companies) of consequences for each individual drug. Ongoing.
- Further meetings with management and pharmacy planned this week. Will finalise a report with consequence assessment and plan for procedural measures to prevent reoccurrence.
| Organisation | City | Country | Type |
|---|---|---|---|
| Helse Bergen HF | Bergen | Norway | Sponsor (non commercial) |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 9 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-512500-19-00 CLEAN | 1.7 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF biobank | 3.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF main_CLEAN | 4.0.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_group 4 | 4.2.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_group 5 | 4.3.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_retreatment | 4.1.2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Darzalex | N/A |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis | 1.7 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-06-19 | Norway | Acceptable 2024-07-09
|
2024-07-09 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-12-04 | Norway | Acceptable 2025-02-17
|
2025-02-18 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-09-25 | Norway | Acceptable 2025-11-12
|
2025-11-12 |