E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Sporadic Inclusion Body Myositis (sIBM) |
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E.1.1.1 | Medical condition in easily understood language |
progressive weakening of the muscles |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10075052 |
E.1.2 | Term | Sporadic inclusion body myositis |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the efficacy (based on the Inclusion Body Myositis Functional Rating Scale [IBMFRS]) of early versus delayed start (i.e., at 20 months) of arimoclomol treatment of sIBM. |
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E.2.2 | Secondary objectives of the trial |
Secondary:
• To determine the safety and tolerability of long-term treatment of sIBM with arimoclomol
• To determine the efficacy (on secondary efficacy endpoints) of early versus delayed start of arimoclomol treatment of sIBM
Exploratory:
• To establish the long-term efficacy of arimoclomol as determined by magnetic resonance imaging (MRI) parameters.
• To explore population pharmacokinetics (popPK) and popPK/PD. |
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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 |
Magnetic Resonance Imaging (MRI) Sub-study in Patients Participating in IBM-OLE
The objective of this MRI sub-study is to characterise muscle changes using MRI in a subset of patients participating in the main IBM-OLE study. |
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E.3 | Principal inclusion criteria |
1. Patient is able to comprehend and is willing to provide written informed consent and is capable and willing to comply with trial procedures.
2. Patient has completed the IBM4809 trial on treatment with IMP. |
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E.4 | Principal exclusion criteria |
1. Known or suspected allergy or intolerance to arimoclomol or its constituents.
2. Exposure to any other investigational treatment within 30 days or <5 half-lives of the baseline visit or taking part or planning to take part in another interventional trial.
3. Significant protocol deviation in the blinded IBM4809 trial based on the investigator’s judgement in discussion with the medical monitor.
4. Women who are lactating or pregnant, or sexually active female subjects of child-bearing potential* intending to become pregnant or unwilling to use a highly effective method of contraception** during the trial through 1 month after the last dose of trial medication. Sexually active males with female partners of child-bearing potential* unwilling to use a condom with or without spermicide in addition to the birth control used by their partners during the trial until 3 months after the last dose of trial medication unless surgically sterile (vasectomy).
* Non child-bearing potential is defined as post-menopausal (minimum of 12 months with no menses and follicle-stimulating hormone in the post-menopausal range) or sterilisation (hysterectomy, oophorectomy, or bilateral tubal ligation).
** Highly effective methods of contraception include combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable); intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion; and vasectomised partner.
According to the recommendations from the Clinical Trial Facilitation Group (CTFG, 2014), sexual abstinence is considered a highly effective birth control method only if it is defined as refraining from heterosexual intercourse during the trial until 1 month after the last dose of trial medication (for female subjects of child-bearing potential) and for 3 months after the last dose of trial medication (for male subjects with female partners of child-bearing potential). The reliability of sexual abstinence needs to be evaluated by the investigator in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.
5. Any concurrent condition that in the investigator’s opinion will significantly interfere with assessment of safety or efficacy.
6. Inability to comply with the protocol-specified procedures/evaluations and scheduled visits as per the investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy endpoints:
• Primary efficacy endpoint: Change from baseline to Month 20 in the IBMFRS total score
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Endpoint evaluation will be checked at every visit for Efficacy. |
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E.5.2 | Secondary end point(s) |
• Secondary efficacy endpoints: Change from baseline to Month 20 in secondary efficacy parameters
Exploratory endpoints:
• Population pharmacokinetics (popPK) and popPK/PD (reported separately)
Safety endpoints:
• Safety parameters (AEs, SAEs, clinical safety laboratory values, vital signs, C-SSRS) assessed throughout the extension trial |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Endpoint evaluation will be checked at every visit for Safety.
Exploratory endpoints will be evaluated at Month 9. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
biomarker CN1A Ab testing and biobanking for future analyses. |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
This Phase 3b, multicenter, nonrandomized, open-label, uncontrolled clinical extension trial |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |