E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050238 |
E.1.2 | Term | Spinal fusion NOS |
E.1.2 | System Organ Class | 100000021566 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to assess the safety and efficacy of ALLOB® in rescue interbody fusion over 12 months in patients suffering from failed lumbar fusion at one or two level(s). Safety: At each visit, subjects will be assessed for the potential occurrence of any AE or SAE related to the product or to the procedure, using patient open non-directive questionnaires, vital signs and laboratory measurements. Efficacy: The efficacy of the treatment will be evaluated at Month 12: - Radiologically (progression of the lumbar fusion): the Fusion Score as assessed by CT-scan vs. baseline. - Clinically (functional disability): the changes in ODI 2.1a vs. baseline.
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E.2.2 | Secondary objectives of the trial |
The other efficacy endpoints are: -Number of patients requiring a rescue surgery for failed rescue fusion -Changes in ODI 2.1a at each FU visit -Changes in Back and Leg Pain VAS at each FU visit -Changes in Global Disease Evaluation VAS at each FU visit -Lumbar fusion progression using the Fusion Score at Month 6, 9, 12 -Mean time to lumbar fusion -Changes of intervertebral mobility at Month 6, 9, 12 -Integrity of instrumentation and surrounding bones at Month 6, 9, 12 -Changes of segmental lordosis at Month 6, 9, 12 -Changes of lumbar lordosis at Month 6, 9, 12 -Changes of disc height at Month 6, 9, 12 -Assessment of bone metabolism at each FU visit -Blood loss during procedure -Operating time -Number of per- and post-operative complications -Hospital stay duration -Assessment of ALLOB® biodistribution at Hour 4, 24, 48, 72 -Assessment of bone remodelling/formation at Month 3, 6, 9
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
ALLOB® biodistribution and bone remodelling/formation The objective of this sub-study is to investigate the biodistribution, locally and systematically, of radio-labelled ALLOB® cells after the implantation at the failed lumbar fusion level. The timepoints for biodistribution are 4 ± 2 hours (if the patient is capable to undergo the procedure), 24 ± 4 hours, 48 ± 4 hours and 72 ± 4 hours post-implantation. An additional objective is to assess the healing process (bone remodelling/formation) of the failed lumbar fusion level. The timepoints for bone remodelling/formation are the day before implantation, 3 Months, 6 Months and 9 Months post-implantation. The biodistribution sub-study will only be conducted on maximum 6 patients in a single centre.
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E.3 | Principal inclusion criteria |
- Man or woman aged of minimum 18 years old (at the time of treatment) -Diagnosed with a failed lumbar interbody fusion procedure at the time of ALLOB® treatment: - Defined radiologically (as judged by the Investigator) - Of a minimum of 15 months follow-up - Requiring a revision surgery at one or two level(s) between L1 to S1 - Capable to provide a written, dated, and signed informed consent and to understand and comply with the study requirements
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E.4 | Principal exclusion criteria |
Current symptoms and/or signs related to the disease under study - More than two previous spinal surgeries at the lumbar level(s) not involving instrumentation withdrawal - More than two failed interbody fusion at the involved lumbar level(s) - Local active or latent infection at the involved lumbar level(s) - Instrumentation failure (e.g., pedicle screw, interbody cage) requiring revision surgery - Extra-spinal cause of back pain, such as trauma, infection, or tumour at the involved lumbar level(s) - Requiring surgery within the next 12 months (at the time of the implantation)
Current or previous diagnoses, signs and/or symptoms - Positive serology for HIV (defined as positive Anti-HIV 1 and/or 2 and/or positive PCR) - Active hepatitis B (defined as positive HBs Ag and/or positive PCR) - Active hepatitis C (defined as positive Anti-HCV and/or positive PCR) - Global sepsis - Severe renal (defined as a creatinine clearance value < 30 ml/min, calculated with the Cockcroft-Gault formula) or severe hepatic impairment (defined as alanine aminotransferase or aspartate aminotransferase ≥ 3 times the upper normal limit) - Severe diabetes (defined as HbA1C > 8%) - Severe allergy or anaphylaxis - Known allergy to gentamicin - Known allergy to contrast agent (only in case of use of contrast agent during implantation procedure) - Medical condition that could interfere with study participant assessment (e.g., neuromuscular disease, psychiatric disease, paraplegia) - Active autoimmune disease (e.g., sclerodermia, Sjögren syndrome, lupus) - Current or past (within 5 years) malignant neoplasia (except for cured cancers such as non-metastatic thyroid cancer, seminoma, non-melanoma skin cancer…) - Poor general health or concomitant disease that would place the patient in excessive risk to surgery (i.e., significant circulatory or pulmonary problems, or cardiac disease) - History of organ or bone marrow transplantation - History of hypersensitivity to human biological material including blood and blood derived products, documented clinically or by laboratory tests
Current or previous treatment - Previous treatment with ALLOB® - Participation (within 3 months of screening) in another clinical study involving a pharmacological agent - Current or past treatment (within 5 years of screening) for cancer or blood dyscrasia, including but not limited to chemotherapy, radiotherapy, immunotherapy, biotherapy, haematopoietic growth factors and/or anti-angiogenesis treatment (except for cured cancers such as non-metastatic thyroid cancer, seminoma, non-melanoma skin cancer..) - Current (within 6 months of screening) illicit drug abuse (as per local law)
Safety aspects concerning female subjects with childbearing potential - Positive Urine Pregnancy test - Pregnancy - Breast-feeding - Woman with childbearing potential not willing or not able to use reliable contraceptive method for at least 6 weeks prior to screening and during the whole study period (reliable contraceptive methods include orally administered hormonal contraceptives, intrauterine device or surgical intervention (e.g., tubal ligation)
Other exclusion criteria - Body Mass Index (BMI) ≥ 35 kg/m2 - Clinically relevant abnormal ECG (>6-lead or according to standard of care at the hospital), as judged by the Investigator or any medically qualified member of the study care team - Unable to undergo general anaesthesia or a surgical intervention |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety criteria: From the beginning to the end of the main study period at Month 12, study participants will be systematically assessed for the potential occurrence of any AE and SAE related or not to the treatment (i.e., ALLOB® or implantation procedure), using subject open questionnaires, physical examinations and laboratory measurements. Selected safety data will also be investigated during an additional post-study safety follow-up 12 months and 24 months after the end of the study. Efficacy criteria: The following clinical and radiological criteria will be used: - Radiologically (progression of the lumbar fusion): the Fusion Score as assessed by CT-scan (vs. baseline) - Clinically (functional disability): the changes in ODI 2.1a vs. baseline |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The following time points will be used to evaluate over the 12-month follow-up period: - Clinical endpoints at baseline and at 6 weeks, 3, 6, 9 and 12 months - Radiological endpoints at baseline and at 6, 9 and 12 months Safety endpoints will be determined at each scheduled visit over the 12-month follow-up period
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E.5.2 | Secondary end point(s) |
The other endpoints will be: - Number (percentage) of patients requiring a rescue surgery for failed rescue fusion at one or more level(s) - Changes in ODI 2.1a at each follow-up visit (vs. baseline) - Changes in Back and Leg Pain VAS at each follow-up visit (vs. baseline) - Changes in Global Disease Evaluation VAS at each follow-up visit (vs. baseline) - Lumbar fusion progression at the treated level(s) using the Fusion Score as assessed by CT-scan at Month 6, 9 and 12 - Mean time to lumbar fusion at the treated level(s) as assessed by CT-scan - Changes of intervertebral mobility at the treated level(s) as assessed by X-ray at Month 6, 9 and 12 (vs. baseline) - Integrity of instrumentation and surrounding bones at the treated level(s) as assessed by CT-scan and X-ray at Month 6, 9 and 12 - Changes of segmental lordosis at treated level(s) as assessed by X-ray at Month 6, 9 and 12 (vs. baseline) - Changes of lumbar lordosis as assessed by X-ray at Month 6, 9 and 12 (vs. baseline) - Changes of disc height at the treated level(s) as assessed by CT-scan at Month 6, 9 and 12 (vs. baseline) - Assessment of bone metabolism using bone biomarkers at each follow-up visit (vs. baseline) - Loss of blood during procedure - Operating time - Number of per-operative and post-operative complications - Duration of hospital stay - Assessment of ALLOB® biodistribution at Hour 4, 24, 48 and 72 − Assessment of bone remodelling/formation at Month 3, 6 and 9 (vs. baseline) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy endpoints will be determined at each scheduled visit over the 12-month follow-up period. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |