A Phase 2 interventional study of OK432 in Lymphatic Malformations, sponsored by Richard JH Smith. Completed at 14 sites in United States. Open to participants aged 6 Months to 17 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-11-23.
Sponsored by Richard JH Smith · Phase 2, Interventional, and Treatment
Standard of care for Lymphatic Malformations has been surgical excision. We have been using OK432/Picibanil (generously supplied by Chugai Pharmaceuticals in Japan) since 1992 with great success for macrocystic disease.
The objective of the study was to provide OK-432 immunotherapy to subjects with macrocystic or mixed (> 50% macrocystic) lymphatic malformations (LMs) and investigate the efficacy and safety of OK 432 as a treatment option in subjects with LMs.
Lymphatic malformations are uncommon tumors that represent localized malformations in the development of the lymphatic system. They typically present in children under 2 years of age and in almost 50% of the cases, are diagnosed at birth. There is neither a racial nor a sexual tendency. The malformations can occur anywhere on the body, but typically they are in the head/neck area.
Morbidity can be significant. Besides the obvious cosmetic deformity caused by these tumors, there is risk of infection and airway compromise and even obstruction. However, effective therapeutic options are limited. Small lesions can be observed, although spontaneous resolution is unlikely. For larger lesions, surgery has been the traditional form of therapy. In the head and neck, in particular, lymphangiomas typically wrap themselves around major neurovascular structures, making total excision removal difficult, if not impossible, and thus the likelihood of recurrence is quite high. Because of these surgical limitations, alternate therapies have been considered; including cryotherapy, diathermy, and chemical sclerotherapy.
The investigators experience with using the drug for macrocystic disease(large cysts) since 1992 in the United States has been very promising compared to traditional surgery. Recurrence rate to date, has been very minimal as well. (\<2%)
After the conclusion of the Phase 2 randomized study, all new subjects who presented with an LM and were eligible for treatment were treated under an open-label protocol for continued access to OK-432. This multicenter, open label study enrolled subjects between September 2005 and November 2017.
42 studies on the registry are indexed under Lymphatic Abnormalities; 17 are open to participants now.
This study's enrollment of 275 is above the median of 46 across 28 interventional studies indexed under Lymphatic Abnormalities.
Browse Lymphatic Abnormalities studies →This is the only study on the registry with Richard JH Smith as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
To be eligible to receive OK432 immunotherapy
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
There is no control in this study. All participants will receive the actual drug -OK432. With each injection they may receive 0.01 to 0.05mg/mL 6-12 weeks apart up to 4 injections total.
Drug: OK432
OK432 will be injected at dosage of 0.01 to 0.05 mg/mL 6-12 weeks apart up to 4 injections total.
Also known as: Picibanil
Number of Participants With Clinical Success at 1 to 6 Months Post-Therapy as Assessed by Imaging
Clinical success was defined as having either a complete (90% 100%) or substantial (60% 89%) reduction in lymphatic malformation (LM) volume after treatment. Response was determined using post treatment imaging studies at approximately 1 to 6 months after completion of treatment
Time frame: 1 to 6 Months Post-Therapy
Number of Participants With Clinical Response 1 to 6 Months Post-Therapy as Assessed by Imaging
Number of participants who demonstrated a complete (90%-100% reduction in LM volume), substantial (60%-89% reduction in LM volume), intermediate (20%-59% reduction in LM volume), or no (\< 20% reduction in LM volume) response 1 to 6 months post-therapy as assessed by imaging
Time frame: 1 to 6 Months Post-Therapy
Number of Participants With Investigator-Evaluated Overall Response
Investigator evaluated post-therapy clinical response based on physical exam and/or ultrasound was categorized as "Clinical Improvement" or "No Change" in the size of the cyst.
Time frame: 1 to 6 Months Post-Therapy
Change From Baseline in Lesion Volume
Percent change from baseline in lesion volume - pre-therapy to post therapy assessed by imaging.
Time frame: Baseline and 1 to 6 Months Post-Therapy
The study was conducted in 14 centers across the United States between September 2005 and November 2017.
| Milestone | OK-432 |
|---|---|
| Started | 275 |
| Safety population | 275 |
| Modified intention to treat population | 143 |
| Completed | 209 |
| Not completed | 66 |
| Withdrew: Physician decision | 3 |
| Withdrew: Withdrawal by subject | 4 |
| Withdrew: Lost to follow-up | 5 |
| Withdrew: Administrative | 4 |
| Withdrew: Other | 2 |
| Withdrew: Unknown or missing completion status | 48 |
Clinical success was defined as having either a complete (90% 100%) or substantial (60% 89%) reduction in lymphatic malformation (LM) volume after treatment. Response was determined using post treatment imaging studies at approximately 1 to 6 months after completion of treatment
| Participants | OK-432 |
|---|---|
| Number of Participants With Clinical Success at 1 to 6 Months Post-Therapy as Assessed by Imaging | 57 |
Number of participants who demonstrated a complete (90%-100% reduction in LM volume), substantial (60%-89% reduction in LM volume), intermediate (20%-59% reduction in LM volume), or no (\< 20% reduction in LM volume) response 1 to 6 months post-therapy as assessed by imaging
| Participants | OK-432 |
|---|---|
| Number of subjects who achieved a complete response | 43 |
| Number of subjects who achieved a substantial response | 14 |
| Number of subjects who achieved an intermediate response | 5 |
| Number of subjects who achieved no response | 16 |
Investigator evaluated post-therapy clinical response based on physical exam and/or ultrasound was categorized as "Clinical Improvement" or "No Change" in the size of the cyst.
| Participants | OK-432 |
|---|---|
| Number of Participants With Investigator-Evaluated Overall Response | 80 |
Percent change from baseline in lesion volume - pre-therapy to post therapy assessed by imaging.
| percent change | OK-432 |
|---|---|
| Change From Baseline in Lesion Volume | -44.92 ± 110.561 |
Collected over Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| OK-432 | 0/275 (0%) | 11/275 (4%) | 112/114 (98.2%) |
| Event | OK-432 |
|---|---|
| PyrexiaGeneral disorders | 5/275 |
| VomitingGastrointestinal disorders | 3/275 |
| Injection site swellingGeneral disorders | 2/275 |
| SwellingGeneral disorders | 2/275 |
| DehydrationMetabolism and nutrition disorders | 2/275 |
| Decreased appetiteMetabolism and nutrition disorders | 1/275 |
| HypophagiaMetabolism and nutrition disorders | 1/275 |
| OdynophagiaGastrointestinal disorders | 1/275 |
| FuruncleInfections and infestations | 1/275 |
| Infected cystInfections and infestations | 1/275 |
| Event | OK-432 |
|---|---|
| SwellingGeneral disorders | 112/114 |
| PainGeneral disorders | 112/114 |
| RednessGeneral disorders | 110/114 |
| FeverGeneral disorders | 72/114 |
| FatigueGeneral disorders | 66/114 |
| Decreased appetiteGeneral disorders | 63/114 |
| Nausea/vomitingGeneral disorders | 35/114 |
| HeadacheGeneral disorders | 32/114 |
| ChillsGeneral disorders | 21/114 |
| Joint painGeneral disorders | 18/114 |
The Safety Population included all enrolled subjects that have been treated with at least one injection of OK-432. Results were based on a retrospective analysis of source-verified data and only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses.
| Age, Continuous(years) | OK-432 |
|---|---|
| Mean | 5.481 ± 6.6382 |
| Sex: Female, Male(Participants) | OK-432 |
|---|---|
| Female | 151 |
| Male | 123 |
| Race/Ethnicity, Customized(Participants) | OK-432 |
|---|---|
| Hispanic or Latino | 36 |
| American Indian or Alaska Native | 2 |
| White | 191 |
| Black or African American | 29 |
| Asian | 10 |
| Other | 7 |
| Region of Enrollment(participants) | OK-432 |
|---|---|
| United States | 275 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Oct 2005 to primary completion in Apr 2018, 150 months.
Results were first posted in Oct 2021, 3 years 5 months after primary completion.
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Studies of the drug tested here: Picibanil