Trial comparing intra-discal allogeneic adult BM-MSC therapy and sham-treated controls in subjects with chronic low back pain due to lumbar degenerative disc disease unresponsive to conventional therapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Hospital Of Montpellier

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

12 Jul 2020 → ongoing

Decision date (initial)

2024-11-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

European Commission

External identifiers

EU CT number

2023-510000-45-00

EudraCT number

2017-002092-25

ClinicalTrials.gov

NCT03737461

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The first co-primary objective is to assess the efficacy of intradiscal injection of allogeneic BM-MSCs in reducing chronic low back pain due to lumbar DDD using the visual analog scale (VAS) and functional status assessed by the Oswestry disability index (ODI) after 12 months of treatment, defining a responder as a patient with an improvement of VAS for pain of at least 20% and 20 mm between baseline and month 12, or with an improvement of ODI of 20% between baseline and month 12.
The second co-primary objective is to assess the efficacy of intradiscal injection of allogeneic BM-MSCs in increasing disc fluid content, measured by quantitative Magnetic Resonance Imaging, between baseline and month 12.

Secondary objectives 10

1. To evaluate the efficacy of intradiscal injection of allogeneic BM-MSCs using VAS and ODI after 3, 6 and 24 months of treatment, defining responders in case of at least 20% of improvement in VAS for pain (with at least 20 mm decrease from baseline on VAS scale) or ODI compared to baseline
2. Assess efficacy of allogeneic stem cell treatments for DDD on modification of VAS, considered as a continuous measure, between baseline and 3, 6, 12 and 24 months.
3. Evaluate modification of disability (ODI) and quality of life (SF-36 scores), considered as continuous measures, between baseline and 3, 6, 12 and 24 months.
4. Evaluate modification of affected disc by quantitative Magnetic Resonance Imaging (MRI) signal measurements in T2 and T1spin/echo and T1rho weighted images between baseline, 6, 12, and 24 months used as an indication of disc fluid (T2) and glycosaminoglycan (GAG) content (T1rho).
5. Assess modification of employment and work status between baseline and months 12 and 24.
6. Assess safety and tolerability, measured by nature and severity of adverse events. Both the acute and long-term safety will be analysed. The incidence of potentially procedure related adverse events such as infections, bleedings, nerve irritations and nerve injuries with its possible consequences paraesthesia and paralysis will be evaluated. Adverse events will be reported using clinical review and questionnaires for pain, disability and quality of life along the study.
7. Consumption of medications to relieve pain such as type and dose of analgesics will be evaluated. Paracetamol (acetaminophen) and levels 2 analgesics will be assessed throughout the study at each visit.
8. Assess immune response associated with allogeneic cells injection (quantification of anti-HLA in all patients).
9. Assess the safety of local MSC injection on the systemic immune system (immunomonitoring sub-study)
10. Assess the medical and non-medical costs

Conditions and MedDRA coding

Degenerative Disc Disease

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age between 18 and 60 years at pre-screening visit
2. Symptomatic chronic low back pain unresponsive to conservative therapy (including pain medication with level 2 analgesics in failure or intolerant to level during at least 1 month) for at least 3 months
3. DDD assessed by (Pfirrmann’s score modified Griffith et al) grade 4 to 7 at one level. If second level, it should be adjacent (Pfirrmann’s score 1-4 maximum)
4. Low back Pain at screening > 40 mm on VAS (0-100)
5. NSAID washout of at least 2 days before screening
6. Painkillers washout of at least 24 hours before screening

Exclusion criteria 24

1. Congenital or acquired diseases leading to spine deformations that may upset cell application (hyperlordosis, scoliosis, isthmus lesion, sacralisation and hemisacralisation)
2. Symptomatic posterior lumbo-articular osteoarthritis or predominant facet syndrome (osteophyte and facet hypertrophy)
3. Prior to the screening visit, has received: Oral corticosteroid therapy within the previous 3 months, OR Intramuscular, intravenous or epidural corticosteroid therapy within the previous 3 months
4. Spinal segmental instability (defined by lumbar dynamic X-Ray in extension/flexion with antero-post translation > 3 mm and/or angular mobility > 15°)
5. Spinal canal stenosis (Schizas score > B)
6. History of spinal infection
7. History of lumbar disc herniation with non truncated sciatica or cruralgia, as well as lumbar cysts and radiculopathy
8. Previous discal puncture or previous spine surgery
9. DDD on 2 or 3 levels but not adjacent, or DDD with modic 2 or 3 phases
10. Patients contre-indicated to intravertebral disc rescue surgery
11. Patients who have the risk to undergo a surgery in the next 6 months
12. Obesity with body mass index (BMI in Kg/size in m2) greater than 35 (obesity grade II)
13. Participation in another clinical trial or treatment with another investigational product within 30 days prior to inclusion in the study
14. Abnormal blood tests: hepatic (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST] >1.5 × upper limit of normal [ULN]), renal, pancreatic or biliary disease, blood coagulation disorders, anemia or platelet count of <100 × 10^9/L
15. Significant medical problems, such as uncontrolled hypertension, symptomatic heart failure; or any other clinically relevant condition or current medication that in the opinion of the investigator contra-indicates the use of any of the study or rescue medications
16. Pregnant or lactating women, or premenopausal women not using an acceptable form of birth control, are ineligible for inclusion. Contraception has to be maintained during treatment and until the individual end of the study (M24). In each case of delayed menstrual period (over one month between menstruations) confirmation of absence of pregnancy is strongly recommended. Methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation : oral, injectable, implantable, intrauterine device (IUD), intrauterine hormone-releasing system ( IUS), bilateral tubal occlusion, vasectomised partner, sexual abstinence are ineligible for inclusion.
17. Positive serology for following infection: Syphilis, HIV, Hepatitis B, Hepatitis C or HTLV
18. Contraindication to MRI assessed by the investigator
19. Intolerance or allergy to local anesthesia
20. Any history of Cancer or immunodeficiency disease
21. History of transfusion or transplantation
22. Current sick leave due to work accident
23. Prisoners or subjects who are involuntary incarcerated
24. Patients subject to legal protection measures

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Clinical response is defined as pain relief of at least 20% and 20 mm decrease on VAS scale between baseline and month 12, or 20% improvement of functional index ODI at month 12 compared to baseline. VAS pain scale (0 – 100, where 0 represents no pain and 100 represents the worst pain imaginable). Oswestry disability index scale ranges from 0 to 50 (0%–20%:minimal disability; 20%–40%:moderate disability; 40%–60%:severe disability; 60%–80%:crippled; 80%–100%:bed-bound/exaggerating their symptoms
2. Fluid content of the discs will be determined from T2-weighted sagittal images, and measured in the affected disc segment and in the contiguous 3 to 5 segments (Methods and Orozco et al). The fluid content values of the affected discs will be normalized to the values obtained from the healthy discs in the same individual (average value of the healthy discs). The change in fluid content is expressed as the ratio of fluid content at months 12 vs fluid content at baseline.
3. Evolution of affected disc(s) by quantitative Magnetic Resonance Imaging (MRI) density measurements in T2 and T1spin/echo and T1rho weighted images performed at screening, 12 and 24 months used as an indication of disc fluid and GAG content. The "quality" of the patient's lumbar disc will be monitored non-invasively using T2-weighted MRI sagittal images and, in T1spin/echo MRI.

Secondary endpoints 7

1. Disability and quality of life evolution include Short Form (SF)-36 scores, global assessment by the patient and the physician. Overall pain intensity in the lumbar spine (1 = none, 2 = mild, 3 = moderate, 4 = severe, 5 = extreme); patient's global assessment of disease activity (1 = very good, 2 = good, 3 = fair, 4 = poor, 5 = very poor); physician's global assessment of disease activity (1 = very good, 2 = good, 3 = fair, 4 = poor, 5 = very poor)
2. de-/increase in rescue painkillers medication
3. drug consumption of painkillers
4. Employment and work status
5. medical and non-medical costs
6. Immune response
7. Safety Outcomes

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Hospital Of Montpellier

Sponsor organisation

University Hospital Of Montpellier

Address

191 Avenue Du Doyen Gaston Giraud

City

Montpellier Cedex 5

Postcode

34295

Country

France

Scientific contact point

Organisation

University Hospital Of Montpellier

Contact name

Christian JORGENSEN

Public contact point

Organisation

University Hospital Of Montpellier

Contact name

Christian JORGENSEN

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 4 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