I am very excited and proud to be attending and speaking at the first European Oratoria-HAND, or O’Hand, study investigator meeting in Barcelona. With Chariot-MS, the O’HAND study is the culmination of more than 4 years of work and campaigning for Barts-MS.
However, our #ThinkHand campaign will only be considered a true success if we get a positive outcome from one of our studies and a DMT gets licensed to protect, or delay loss of, hand and arm function in people with more advanced MS. These trials have the potential to change the field and make more advanced MS modifiable. Many cynics think we are wasting our time. But if you have MS and you lose your lower limb function you become dependent on your hand and arms to maintain your independence. In other words, your arms become your legs.
The following is my presentation from the meeting, which you can download from my bespoke SlideShare site.
| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- EDSS score at screening and baseline >= 3.0 to 8.0, inclusive
- Disease duration from the onset of MS symptoms:
Less than 15 years in patients with an EDSS at screening > 5.0 Less than 10 years in patients with an EDSS at screening <= 5.0
- Documented history or presence at screening of at least one of the following laboratory findings in a cerebrospinal fluid specimen: Elevated IgG index or one or more IgG oligoclonal bands detected by isoelectric focusing
- Screening and baseline 9-HPT completed in > 25 seconds (average of the two hands)
- Ability to complete the 9-HPT within 240 seconds with each hand at screening and baseline
- Patients previously treated with immunosuppressants, immunomodulators, or other immunomodulatory therapies must undergo an appropriate washout period according to the local label of the immunosuppressant/immunomodulatory drug used
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraceptive methods during the treatment period and for 6 months after the final dose of ocrelizumab. Adherence to local requirements, if more stringent, is required.
- For female patients without reproductive potential: Women may be enrolled if post-menopausal unless the patient is receiving a hormonal therapy for her menopause or if surgically sterile
Exclusion Criteria:
- History of relapsing-remitting or secondary progressive MS at screening
- Confirmed serious opportunistic infection including: active bacterial, viral, fungal, mycobacterial infection or other infection, including tuberculosis or atypical mycobacterial disease
- Patients who have or have had confirmed or a high degree of suspicion of progressive multifocal leukoencephalopathy (PML)
- Known active malignancy or are being actively monitored for recurrence of malignancy
- Immunocompromised state
- Receipt of a live-attenuated vaccine within 6 weeks prior to randomization
- Inability to complete an MRI or contraindication to Gd administration.
- Patients requiring symptomatic treatment of MS and/or physiotherapy who are not on a stable regimen. Patients must not initiate symptomatic treatment of MS or physiotherapy within 4 weeks of randomization.
- Contraindications to mandatory premedications for infusion-related reactions, including:
uncontrolled psychosis for corticosteroids and closed-angle glaucoma for antihistamines
- Known presence of other neurologic disorders
- Pregnant or breastfeeding, or intending to become pregnant during the study and 6 months after last infusion of the study drug
- Lack of peripheral venous access
- Significant, uncontrolled disease, such as cardiovascular, pulmonary, renal, hepatic, endocrine or gastrointestinal, or any other significant disease that may preclude patient from participating in the study
- Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
- History of alcohol or other drug abuse
- History of primary or secondary immunodeficiency
- Treatment with any investigational agent within 24 weeks prior to screening (Visit 1) or 5 half-lives of the investigational drug (whichever is longer), or treatment with any experimental procedure for MS
- Previous treatment with B-cell targeting therapies
- Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation
- Any previous history of transplantation or anti-rejection therapy
- Treatment with IV Ig or plasmapheresis within 12 weeks prior to randomization
- Systemic corticosteroid therapy within 4 weeks prior to screening
- Positive serum hCG measured at screening or positive urine β-hCG at baseline
- Positive screening tests for hepatitis B
- Any additional exclusionary criterion as per ocrelizumab (Ocrevus®) local label, if more stringent than the above
- Lack of MRI activity at screening/baseline if more than 650 patients without MRI activity have already been enrolled, as defined by T1 Gd+ lesion(s) and/or new and/or enlarged T2 lesion(s) in the screening, to ensure that at least 350 patients with MRI activity will be randomized
Eligibility Criteria for Open-Label Extension Phase:
- Completed the double-blind treatment phase of the trial or have received PDP OCR in the FU1 phase, and who, in the opinion of the investigator, may benefit from treatment with Ocrelizumab. Patients who withdrew from study treatment and received another disease-modifying therapy (DMT) or commercial ocrelizumab will not be allowed to enter in the OLE phase.
- Meet the re-treatment criteria for ocrelizumab
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraceptive methods during the treatment period and for 6 months after the final dose of ocrelizumab. Adherence to local requirements, if more stringent, is required.
- For female patients without reproductive potential: Women may be enrolled if post-menopausal unless the patient is receiving a hormonal therapy for her menopause or if surgically sterile
CoI: I am the principal investigator on the O’Hand study
There seems to be an assumption that MS disability always creeps from the feet up. One of my earlier symptoms was deteriorating hand function, just left. Followed by my whole left side . Now it’s accompanied by poorer right hand co ordination, my right leg is relatively unscathed, apart from the extra stress on it from taking the strain of lop sidedness . We are all very individual in our function loss
Yes, you are correct all MSers are different. But on average the legs go first then the hands; this patter hit about 80% of MSers. Other presentations may be progressive visual failure, cerebellar/sensory (ataxia or unsteadiness of gait), hemiplegia, dementia (cognitive impairment), etc.
What dictates these less common presentations is probably a slowly expanding lesion of SEL in a specific site. The latter is part of smouldering MS.