BOTOX(RegisteredTM) Treatment of Pediatric Lower Limb Spasticity: Open-label Study Protocol 191622-112

Study ID
STU 112012-079

Cancer Related
No

Healthy Volunteers
No

Study Sites

Contact
Kara Lorduy
214-456-7000
kara.lorduy@childrens.com

Principal Investigator
Fatma Gul

Summary

This is a multicenter, open-label study evaluating the safety of repeated treatments of BoToX in dynamic muscle contracture in pediatric patients with lower limb spasticity due to cerebral palsy. Patients who successfully completed allergan Study 191622-111 without major protocol deviations (eg, noncompliance to protocol-required procedures) may be eligible for enrollment in this study (rollover patients) if they meet the inclusion/exclusion criteria. additionally, if the participant has a significantly affected lower limb, they may receive the BoToX treatment for that limb as well.

also, de novo patients (or those individuals who did not participate in allergan Study 191622-111) who meet inclusion/exclusion criteria may be enrolled in this study. Depending on the number of rollover patients from Study 191622-111 and the dropout rate for the present study, enrollment of de novo patients may be limited. The study duration will be approximately 60 weeks. The total number of clinic visits will depend on the number and timing of treatments received by the patient. There will be a total of approximately 12 clinic visits for de novo patients, approximately 11 clinic visits for rollover patients who transitioned from Study 191622-111, and up to 5 telephone follow-up visits for all patients. Qualified rollover patients do not have to be re-screened for the current study; the exit visit from Study 191622-111 becomes the day 1 visit for this study after the patient signs the Study 191622-112 informed consent and assent (as applicable). These visits allow up to 5 treatment cycles with 12 weeks between treatments.

For this study, visits based on day 1 are referred to by [Quote]study week[Quote] and visits based on treatment are referred to by [Quote]treatment cycle week.[Quote] Retreatments should occur every 12 to 14 weeks (considering the + 2-week visit window) if the patient meets the retreatment criteria. if the patient does not meet the retreatment criteria during the 12 to 14-week window, he or she may be treated any time up to study week 48 (the last opportunity for retreatment) but should be evaluated at least every 6 weeks (calculated from the latest treatment visit date) until he or she meets the retreatment criteria or until study week 48. The exit visit will be study week 48 unless the patient receives treatment after study week 36, in which case the exit visit will be 12 weeks after the last treatment.

There will be up to 5 treatment cycles in the study. For the first treatment cycle, de novo patients (who did not participate in allergan Study 191622-111) are to receive a total of 8 u/kg (not to exceed 300 u) either in a single affected lower limb or divided between both study limbs (referred to as the study lower limb or study lower limbs).
Rollover patients (who participated in allergan Study 191622-111) during the first treatment cycle may receive up to a maximum of 8 u/kg (not to exceed 300 u) in the same lower limb that was treated in Study 191622-111 (referred to as the study lower limb). Patients with clinically significant upper limb spasticity may be eligible to receive BoToX treatment in an affected upper limb up to a maximum of 8 u/kg (not to exceed 300 u). The combined lower and upper limb dose should not exceed 8 u/kg or 300 u, whichever is lower, during the first cycle.

For treatment cycles 2 through 5, the maximum dose for a single lower limb or a single upper limb remains the same as for treatment cycle 1; the maximum dose for combined upper and lower limbs or for both lower limbs only for diplegic patients can be increased to 10 u/kg (not to exceed 340 u). if a patient meets the retreatment criteria, including no indication of an unacceptable safety risk, and it is considered clinically appropriate by the investigator, the patient should receive at least 4 u/kg in the study lower limb(s) every 12 to 14 weeks, with the total dose not to exceed the maximum specified for each treatment cycle.

Participant Eligibility

The following are inclusion criteria for patients who are transitioning from Allergan Study 191622-111 (
* rollover
* patients).

* Eligible patients who successfully completed Allergan Study 191622-111 without major protocol
deviations (eg, noncompliance to protocol-required procedures) and who, in the investigator[Single Quote]s
clinical judgment, did not experience an adverse event that may indicate an unacceptable safety
risk for additional BOTOX treatments

* Stable medical condition in the investigator[Single Quote]s opinion

* Written informed consent has been obtained from parent/legally authorized representative

* Written minor assent has been obtained in accordance with local laws and institutional review
board (IRB)/independent ethics committee (IEC) requirements

* Written documentation has been obtained in accordance with the relevant country and local
privacy requirements, where applicable (eg, Written Authorization for Use and Release of Health
and Research Study Information for United States [US] sites and written Data Protection consent
for European Union [EU] sites)

* Negative urine pregnancy test at day 1 visit (for females of childbearing potential, defined as
females post menarche)

The following are inclusion criteria for de novo patients:

* Male or female, 2 to 16 years and 11 months of age (prior to 17th birthday) at day 1 visit

* Minimum weight of 10 kg at the screening and day 1 visits

* Monoplegic, hemiplegic, or diplegic patients with cerebral palsy with dynamic muscle contracture
(spasticity confirmed by Hypertonia Assessment Tool [HAT]) of the ankle plantar flexors.
Equinovarus and equinovalgus deformities are acceptable.

* MAS-B score >= 2 for the ankle plantar flexors and minimum range of dorsiflexion of 0 degrees of
the ankle with knee fully extended in the study limb at the screening and day 1 visits

* Gross Motor Function Classification System x Expanded and Revised (GMFCS-E&R) level I to
IV at the screening visit

* Patients who are on anti-spastic medications or muscle relaxants (eg, oral baclofen, tizanidine,
dantrolene, scopolamine [oral or patch], vigabatrin, or benzodiazepine therapy) must be on a stable
dose and regimen for at least 30 days prior to the day 1 visit

* Patients who are on anti-epileptic medications must be on a stable dose and regimen for at least
30 days prior to the day 1 visit

* Written informed consent has been obtained from parent/legally authorized representative

* Written minor assent has been obtained in accordance with local laws and IRB/IEC requirements

* Written documentation has been obtained in accordance with the relevant country and local
privacy requirements, where applicable (eg, Written Authorization for Use and Release of Health
and Research Study Information for US sites and written Data Protection consent for EU sites)

* Negative urine pregnancy test at the screening and day 1 visits (for females of childbearing
potential, defined as females post menarche)